AstraZeneca Clinical Trials Website

Olaparib in gBRCA Mutated Pancreatic Cancer whose Disease Has Not Progressed on First Line Platinum-Based Chemotherapy (POLO)

Recruitment Status:
Active, not recruiting

Sponsor:
AstraZeneca

Collaborator:

Myriad Genetics - BRCAnalysis test for FDA Premarket Approval (PMA)

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Information Provided by (Responsible Party):
AstraZeneca

ClinicalTrials.gov Identifier:
NCT02184195

Verification:
Verified 01 May 2020 by AstraZeneca

History of Changes:
ClinicalTrials.gov

Purpose

A Phase III, Randomised, Double Blind, Placebo Controlled, Multicentre
Study of Maintenance Olaparib Monotherapy in Patients with gBRCA
Mutated Metastatic Pancreatic Cancer whose Disease Has Not Progressed on
First Line Platinum Based Chemotherapy

Official Title:	A Phase III, Randomised, Double Blind, Placebo Controlled, Multicentre Study of Maintenance Olaparib Monotherapy in Patients with gBRCA Mutated Metastatic Pancreatic Cancer whose Disease Has Not Progressed on First Line Platinum Based Chemotherapy
Study Type:	Interventional
Overall Recruitment Status:	Active, not recruiting
Study Start Date:	16 December 2014
Study Start Date Type:	Actual
Primary Completion Date:	15 January 2019
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment

Condition	Intervention	Phase
germline BRCA1/2 mutations and metastatic adenocarcinoma of the pancreas	Drug: Olaparib Drug: Olaparib Drug: Placebo Drug: Placebo	Phase 3

Ages Eligible for Study:	18 Years to 130 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:
-Histologically or cytologically confirmed pancreas adenocarcinoma receiving initial chemotherapy for metastatic disease and without evidence of disease progression on treatment
-Patients with measurable disease and/or non-measurable or no evidence of disease
assessed at baseline by CT (or MRI where CT is contraindicated) will be entered in
this study.
-Documented mutation in gBRCA1 or gBRCA2 that is predicted to be deleterious or
suspected deleterious
- Patients are on treatment with a first line platinum-based (cisplatin, carboplatin or
oxaliplatin) regimen for metastatic pancreas cancer, have received a minimum of 16
weeks of continuous platinum treatment and have no evidence of progression based
on investigator’s opinion.
-Patients who have received platinum as potentially curative treatment for a prior
cancer (eg ovarian cancer) or as adjuvant/neoadjuvant treatment for pancreas cancer
are eligible provided at least 12 months have elapsed between the last dose of
platinum-based treatment and initiation of the platinum-based chemotherapy for
metastatic pancreas cancer.

Major Exclusion Criteria:
-gBRCA1 and/or gBRCA2 mutations that are considered to be non detrimental (eg,
“Variants of uncertain clinical significance” or “Variant of unknown significance”
or “Variant, favour polymorphism” or “benign polymorphism” etc.)
-Progression of tumour between start of first line platinum based chemotherapy for
metastatic pancreas cancer and randomisation.
-Cytotoxic chemotherapy or non-hormonal targeted therapy within 28 days of Cycle
1 Day 1 is not permitted.
-Exposure to an investigational product within 30 days or 5 half lives (whichever is
longer) prior to randomisation
-Any previous treatment with a PARP inhibitor, including Olaparib

Contacts

Contact: AstraZeneca Clinical Study Information Center	1-877-240-9479	information.center@astrazeneca.com
Contact Backup: AstraZeneca Cancer Study Locator Service	1-877-400-4656	astrazeneca@emergingmed.com

Sponsors and Collaborators

AstraZeneca

Myriad Genetics - BRCAnalysis test for FDA Premarket Approval (PMA)

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Locations

Country	Location	Facility	Status
Belgium	Research Site	Antwerpen, Belgium, 2020	Completed
Belgium	Research Site	Brussels (Anderlecht), Belgium, 1070	Completed
Belgium	Research Site	Edegem, Belgium, 2650	Withdrawn
Belgium	Research Site	Leuven, Belgium, 3000	Active, not recruiting
Canada	Research Site	Toronto, Canada, M5G 2M9	Completed
Germany	Research Site	Berlin, Germany, 10967	Active, not recruiting
Germany	Research Site	Berlin, Germany, D-13353	Completed
Germany	Research Site	Bochum, Germany, 44791	Active, not recruiting
Germany	Research Site	Bonn, Germany, 53127	Completed
Germany	Research Site	Dresden, Germany, 01307	Completed
Germany	Research Site	Frankfurt am Main, Germany, 60596	Completed
Germany	Research Site	Freiburg im Breisgau, Germany, 79106	Withdrawn
Germany	Research Site	Hamburg, Germany, 22291	Completed
Germany	Research Site	Hamburg, Germany, 20246	Completed
Germany	Research Site	Hannover, Germany, 30625	Completed
Germany	Research Site	Leipzig, Germany, 04103	Completed
Germany	Research Site	München, Germany, 81675	Active, not recruiting
Germany	Research Site	Schweinfurt, Germany, 97422	Completed
Germany	Research Site	Ulm, Germany, 89081	Completed
Australia	Research Site	Campbelltown, Australia, 2560	Completed
Australia	Research Site	Lilydale, Australia, 3140	Withdrawn
Australia	Research Site	Randwick, Australia, 2031	Active, not recruiting
Australia	Research Site	St Leonards, Australia, 2065	Completed
Australia	Research Site	Woolloongabba, Australia, 4102	Withdrawn
Canada , ON	Research Site	London, ON, Canada, N6A 4L6	Completed
Canada , ON	Research Site	Ottawa, ON, Canada, K1H 8L6	Withdrawn
France	Research Site	Amiens, France, 80054	Completed
France	Research Site	Besançon, France, 25030	Completed
France	Research Site	Bordeaux, France, 33075	Active, not recruiting
France	Research Site	Brest Cedex, France, 29609	Completed
France	Research Site	Clichy Cedex, France, 92118	Active, not recruiting
France	Research Site	La Roche sur Yon, France, 85925	Completed
France	Research Site	LILLE, France, 59020	Active, not recruiting
France	Research Site	Lyon, France, 69008	Withdrawn
France	Research Site	LYON CEDEX 03, France, 69437	Active, not recruiting
France	Research Site	Montpellier, France, 34298	Withdrawn
France	Research Site	Nice, France, 06189	Completed
France	Research Site	PARIS, France, 75014	Completed
France	Research Site	Paris CEDEX 14, France, 75674	Completed
France	Research Site	POITIERS, France, 86021	Active, not recruiting
France	Research Site	Rennes, France, 35042	Withdrawn
France	Research Site	STRASBOURG Cedex, France, 67065	Completed
France	Research Site	Toulouse, France, 31059	Completed
France	Research Site	Villejuif, France, 94800	Completed
Israel	Research Site	Beer Sheva, Israel, 84101	Completed
Israel	Research Site	Haifa, Israel, 3109601	Completed
Israel	Research Site	Holon, Israel, 58100	Completed
Israel	Research Site	Nahariya, Israel, 22100	Active, not recruiting
Israel	Research Site	Petah Tikva, Israel, 4941492	Active, not recruiting
Israel	Research Site	Ramat Gan, Israel, 5265601	Active, not recruiting
Israel	Research Site	Rehovot, Israel, 76100	Completed
Israel	Research Site	Tel Aviv, Israel, 6423906	Active, not recruiting
Israel	Research Site	Zefir, Israel, 7030000	Completed
Spain	Research Site	Barcelona, Spain, 08035	Completed
Spain	Research Site	Girona, Spain, 17007	Active, not recruiting
Spain	Research Site	L'Hospitalet de Llobregat, Spain, 08907	Completed
Spain	Research Site	Madrid, Spain, 28007	Completed
Spain	Research Site	Madrid, Spain, 28034	Completed
Spain	Research Site	Madrid, Spain, 28050	Completed
Spain	Research Site	Madrid, Spain, 28041	Active, not recruiting
Spain	Research Site	Málaga, Spain, 29010	Completed
Spain	Research Site	Pamplona, Spain, 31008	Completed
Spain	Research Site	Sabadell, Spain, 8208	Completed
Spain	Research Site	Santiago de Compostela, Spain, 15706	Completed
Spain	Research Site	Valencia, Spain, 46009	Completed
Spain	Research Site	Zaragoza, Spain, 50009	Completed
United Kingdom	Research Site	Edinburgh, United Kingdom, EH4 2XR	Completed
United Kingdom	Research Site	Glasgow, United Kingdom, G12 0YN	Completed
United Kingdom	Research Site	Leeds, United Kingdom, LS9 7TF	Withdrawn
United Kingdom	Research Site	Liverpool, United Kingdom, L69 3GA	Active, not recruiting
United Kingdom	Research Site	London, United Kingdom, WC1E 6AG	Completed
United Kingdom	Research Site	London, United Kingdom, SE5 9RS	Completed
United Kingdom	Research Site	Manchester, United Kingdom, M20 4BX	Completed
United Kingdom	Research Site	Northwood, United Kingdom, HA6 2RN	Completed
United Kingdom	Research Site	Nottingham, United Kingdom, NG5 1PB	Completed
United Kingdom	Research Site	Surrey, United Kingdom, SM1 2DL	Active, not recruiting
South Korea	Research Site	Seongnam-si, South Korea, 13620	Completed
South Korea	Research Site	Seoul, South Korea, 03080	Active, not recruiting
South Korea	Research Site	Seoul, South Korea, 6351	Active, not recruiting
Netherlands	Research Site	Amsterdam, Netherlands, 1105 AZ	Active, not recruiting
Netherlands	Research Site	Maastricht, Netherlands, 6202 AZ	Withdrawn
United States of America , CA	Research Site	Downey, CA, United States of America, 90241	Withdrawn
United States of America , CA	Research Site	La Jolla, CA, United States of America, 92093	Withdrawn
United States of America , CA	Research Site	Los Angeles, CA, United States of America, 90048	Withdrawn
United States of America , CA	Research Site	Los Angeles, CA, United States of America, 90030	Withdrawn
United States of America , CA	Research Site	Santa Monica, CA, United States of America, 90404	Withdrawn
United States of America , CA	Research Site	Stanford, CA, United States of America, 94305-5720	Active, not recruiting
Canada , QC	Research Site	Montreal, QC, Canada, H2X 3J4	Withdrawn
Canada , QC	Research Site	Sherbrooke, QC, Canada, J1G 2E8	Completed
Italy	Research Site	Ancona, Italy, 60126	Withdrawn
Italy	Research Site	Bologna, Italy, 40138	Completed
Italy	Research Site	Milano, Italy, 20132	Active, not recruiting
Italy	Research Site	Milano, Italy, 20133	Completed
Italy	Research Site	Monserrato, Italy, 09042	Withdrawn
Italy	Research Site	PADOVA, Italy, 35128	Completed
Italy	Research Site	Parma, Italy, 43126	Completed
Italy	Research Site	Pescara, Italy, 65100	Completed
Italy	Research Site	Pisa, Italy, 56126	Withdrawn
Italy	Research Site	Roma, Italy, 00144	Completed
Italy	Research Site	Roma, Italy, 00128	Completed
Italy	Research Site	San Giovanni Rotondo, Italy, 71013	Completed
Italy	Research Site	Verona, Italy, 37134	Active, not recruiting
United States of America , IL	Research Site	Chicago, IL, United States of America, 60637	Completed
United States of America , IL	Research Site	Evanston, IL, United States of America, 60201	Withdrawn
United States of America , MD	Research Site	Baltimore, MD, United States of America, 21287	Active, not recruiting
United States of America , MD	Research Site	Bethesda, MD, United States of America, 20889	Withdrawn
United States of America , PA	Research Site	Philadelphia, PA, United States of America, 19111	Completed
United States of America , Connecticut	Research Site	New Haven, Connecticut, United States of America, 06510-3220	Completed
United States of America , OH	Research Site	Columbus, OH, United States of America, 43210	Completed
United States of America , CO	Research Site	Aurora, CO, United States of America, 80045	Completed
United States of America , FL	Research Site	Boca Raton, FL, United States of America, 33486	Active, not recruiting
United States of America , FL	Research Site	Miami, FL, United States of America, 33136	Withdrawn
United States of America , FL	Research Site	Miami, FL, United States of America, 33136	Active, not recruiting
United States of America , NY	Research Site	Commack, NY, United States of America, 11725	Completed
United States of America , NY	Research Site	New York, NY, United States of America, 10032	Completed
United States of America , NY	Research Site	New York, NY, United States of America, 10022	Completed
United States of America , NY	Research Site	New York, NY, United States of America, 10065	Completed
United States of America , NY	Research Site	Sleepy Hollow, NY, United States of America, 10591	Withdrawn
United States of America , NY	Research Site	West Harrison, NY, United States of America, 10604	Withdrawn
United States of America , MO	Research Site	St Louis, MO, United States of America, 63110	Completed
United States of America , SC	Research Site	Spartenburg, SC, United States of America, 29303	Withdrawn
Canada , Quebec	Research Site	Montreal, Quebec, Canada, H3T 1E2	Completed
United States of America , Arizona	Research Site	Gilbert, Arizona, United States of America, 85234	Completed
United States of America , California	Research Site	Orange, California, United States of America, 92868-3298	Completed
United States of America , MA	Research Site	Boston, MA, United States of America, 02114-2696	Withdrawn
United States of America , MA	Research Site	Boston, MA, United States of America, 02215	Active, not recruiting
United States of America , WA	Research Site	Seattle, WA, United States of America, 98109	Withdrawn
United States of America , WA	Research Site	Seattle, WA, United States of America, 98104	Completed
Canada , MB	Research Site	Winnipeg, MB, Canada, R2H 2A6	Withdrawn
United States of America , TX	Research Site	Arlington, TX, United States of America, 76012	Withdrawn
United States of America , TX	Research Site	Dallas, TX, United States of America, 75390	Withdrawn
United States of America , TX	Research Site	Houston, TX, United States of America, 77030	Active, not recruiting
United States of America , New York	Research Site	New York City, New York, United States of America, 10015	Completed
United States of America , New York	Research Site	Rockville Centre, New York, United States of America, 11570-1000	Withdrawn
United States of America , NJ	Research Site	Basking Ridge, NJ, United States of America, 07920	Withdrawn
United States of America , DC	Research Site	Washington, DC, United States of America, 20007	Withdrawn

	File name	Description
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	Redacted_SAP	Redacted_SAP

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study randomised patients at a total of 59 study centres in 12 countries: United States of America (13), Germany (8), France (7), Israel (7), Spain (7), United Kingdom (6), Italy (4), Belgium (2), Republic of Korea (2), Australia (1), Canada (1) and Netherlands (1).

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Screening Part 1 was only required if a patient’s gBRCAm status was unknown and Screening Part 2 was for patients with known local germline BRCA (gBRCA) test. All other screening parameters were done as per the Study Schedule.

Reporting Groups

	Description
Olaparib 300 mg twice daily (bd)	Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
Placebo	Randomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Participant Flow: Overall Study

	Olaparib 300 mg twice daily (bd)	Placebo
STARTED	92	62
COMPLETED	49	27
NOT COMPLETED	43	35
Patient decision	3	1
Eligibility criteria not fulfilled	0	1
Death	40	29
Lost to Follow-up	0	2
Other	0	2

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
Olaparib 300 mg twice daily (bd)	Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
Placebo	Randomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Baseline Measures

	Olaparib 300 mg twice daily (bd)	Placebo	Total
Number of Participants [units: Participants]	92	62	154
Age Continuous [units: Years] Mean ± Standard Deviation	58.2 ± 10.27	56.4 ± 9.07	57.5 ± 9.81
Sex: Female, Male [units: Participants]
Female	39	31	70
Male	53	31	84
Race (NIH/OMB) [units: Participants]
American Indian or Alaska Native	1	0	1
Asian	4	2	6
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	5	0	5
White	82	59	141
More than one race	0	0	0
Unknown or Not Reported	0	1	1
Ethnicity (NIH/OMB) [units: Participants]
Hispanic or Latino	4	2	6
Not Hispanic or Latino	88	60	148
Unknown or Not Reported	0	0	0

Outcome Measures

1. Primary Outcome Measure: Progression-free survival (PFS) by blinded independent central review (BICR) using modified Response Evaluation Criteria in Solid Tumours. This study used modified RECIST version (v) 1.1 (RECIST v1.1) [ Time Frame: Up to 4 years ]

Measure Type	Primary
Measure Name	Progression-free survival (PFS) by blinded independent central review (BICR) using modified Response Evaluation Criteria in Solid Tumours. This study used modified RECIST version (v) 1.1 (RECIST v1.1)
Measure Description	To determine the efficacy of olaparib maintenance monotherapy compared to placebo by PFS. The PFS was defined as the time from randomisation until the date of objective radiological disease progression according to modified RECIST v1.1 or death (by any cause in the absence of disease progression) regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to disease progression.
Time Frame	Up to 4 years
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat (ITT): All randomised patients, Myriad confirmed Breast cancer susceptibility gene mutation (gBRCAm) subgroup.

Reporting Groups

	Description
Olaparib 300 mg twice daily (bd)	Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
Placebo	Randomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

	Olaparib 300 mg twice daily (bd)	Placebo
Number of Participants Analyzed [units:participants]	92	62
Progression-free survival (PFS) by blinded independent central review (BICR) using modified Response Evaluation Criteria in Solid Tumours. This study used modified RECIST version (v) 1.1 (RECIST v1.1) [units: Months] Median (95% Confidence Interval)	7.4 (4.14 to 11.01)	3.8 (3.52 to 4.86)

Statistical Analysis 1 for Progression-free survival (PFS) by blinded independent central review (BICR) using modified Response Evaluation Criteria in Solid Tumours. This study used modified RECIST version (v) 1.1 (RECIST v1.1)

Groups^[1]	All groups
Method^[3]	Other [Log-rank test]
P-Value^[4]	0.0038
Hazard Ratio (HR)^[5]	0.531
95% Confidence Interval	( 0.346 to 0.815 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

2. Secondary Outcome Measure: Overall Survival (OS) [ Time Frame: Upto 4 years ]

Measure Type	Secondary
Measure Name	Overall Survival (OS)
Measure Description	To determine the efficacy by assessment of OS of olaparib maintenance monotherapy compared to placebo. The OS was defined as the time from the date of randomization until death due to any cause.
Time Frame	Upto 4 years
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat (ITT): All randomised patients, Myriad confirmed Breast cancer susceptibility gene mutation (gBRCAm) subgroup.

Reporting Groups

	Description
Olaparib 300 mg twice daily (bd)	Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
Placebo	Randomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

	Olaparib 300 mg twice daily (bd)	Placebo
Number of Participants Analyzed [units:participants]	92	62
Overall Survival (OS) [units: Months] Median (95% Confidence Interval)	18.9 (14.85 to 26.15)	18.1 (12.62 to 26.12)

Statistical Analysis 1 for Overall Survival (OS)

Groups^[1]	All groups
Method^[3]	Other [Log-rank test]
P-Value^[4]	0.6833
Hazard Ratio (HR)^[5]	0.906
95% Confidence Interval	( 0.563 to 1.457 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

3. Secondary Outcome Measure: Time from randomisation to second progression (PFS2) [ Time Frame: Up to 4 years ]

Measure Type	Secondary
Measure Name	Time from randomisation to second progression (PFS2)
Measure Description	To determine efficacy by assessment of PFS2 of olaparib maintenance monotherapy compared to placebo. The PFS2 was defined as the time from the date of randomisation to the earliest of the progression event subsequent to that used for the primary variable PFS or death.
Time Frame	Up to 4 years
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat (ITT): All randomised patients, Myriad confirmed Breast cancer susceptibility gene mutation (gBRCAm) subgroup.

Reporting Groups

	Description
Olaparib 300 mg twice daily (bd)	Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
Placebo	Randomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

	Olaparib 300 mg twice daily (bd)	Placebo
Number of Participants Analyzed [units:participants]	92	62
Time from randomisation to second progression (PFS2) [units: Months] Median (95% Confidence Interval)	13.2 (7.75 to 26.15)	9.2 (7.62 to 13.54)

Statistical Analysis 1 for Time from randomisation to second progression (PFS2)

Groups^[1]	All groups
Method^[3]	Other [Log-rank test]
P-Value^[4]	0.2597
Hazard Ratio (HR)^[5]	0.755
95% Confidence Interval	( 0.464 to 1.230 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

4. Secondary Outcome Measure: Time from randomisation to second subsequent therapy or death (TSST) [ Time Frame: Up to 4 years ]

Measure Type	Secondary
Measure Name	Time from randomisation to second subsequent therapy or death (TSST)
Measure Description	To determine the efficacy by assessment of TSST of olaparib maintenance monotherapy compared to placebo. The TSST was defined as time to second subsequent therapy or death.
Time Frame	Up to 4 years
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat (ITT): All randomised patients, Myriad confirmed Breast cancer susceptibility gene mutation (gBRCAm) subgroup.

Reporting Groups

	Description
Olaparib 300 mg twice daily (bd)	Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
Placebo	Randomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

	Olaparib 300 mg twice daily (bd)	Placebo
Number of Participants Analyzed [units:participants]	92	62
Time from randomisation to second subsequent therapy or death (TSST) [units: Months] Median (95% Confidence Interval)	13.2 (8.84 to 20.04)	9.2 (8.34 to 13.14)

Statistical Analysis 1 for Time from randomisation to second subsequent therapy or death (TSST)

Groups^[1]	All groups
Method^[3]	Other [Log-rank test]
P-Value^[4]	0.0825
Hazard Ratio (HR)^[5]	0.678
95% Confidence Interval	( 0.437 to 1.051 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

5. Secondary Outcome Measure: Time from randomisation to first subsequent therapy or death (TFST) [ Time Frame: Up to 4 years ]

Measure Type	Secondary
Measure Name	Time from randomisation to first subsequent therapy or death (TFST)
Measure Description	To determine the efficacy by assessment of TFST of olaparib maintenance monotherapy compared to placebo. The TFST was defined as time to first subsequent therapy or death.
Time Frame	Up to 4 years
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat (ITT): All randomised patients, Myriad confirmed Breast cancer susceptibility gene mutation (gBRCAm) subgroup.

Reporting Groups

	Description
Olaparib 300 mg twice daily (bd)	Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
Placebo	Randomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

	Olaparib 300 mg twice daily (bd)	Placebo
Number of Participants Analyzed [units:participants]	92	62
Time from randomisation to first subsequent therapy or death (TFST) [units: Months] Median (95% Confidence Interval)	8.6 (6.21 to 12.45)	5.7 (4.17 to 6.34)

Statistical Analysis 1 for Time from randomisation to first subsequent therapy or death (TFST)

Groups^[1]	All groups
Method^[3]	Other [Log-rank test]
P-Value^[4]	0.0013
Hazard Ratio (HR)^[5]	0.496
95% Confidence Interval	( 0.324 to 0.760 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

6. Secondary Outcome Measure: Time from randomisation to study treatment discontinuation or death (TDT) [ Time Frame: Up to 4 years ]

Measure Type	Secondary
Measure Name	Time from randomisation to study treatment discontinuation or death (TDT)
Measure Description	To determine the efficacy by assessment of TDT compared to placebo. compared to placebo. The TDT was defined as time to study treatment discontinuation or death.
Time Frame	Up to 4 years
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat (ITT): All randomised patients, Myriad confirmed Breast cancer susceptibility gene mutation (gBRCAm) subgroup.

Reporting Groups

	Description
Olaparib 300 mg twice daily (bd)	Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
Placebo	Randomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

	Olaparib 300 mg twice daily (bd)	Placebo
Number of Participants Analyzed [units:participants]	92	62
Time from randomisation to study treatment discontinuation or death (TDT) [units: Months] Median (95% Confidence Interval)	7.2 (5.52 to 10.84)	3.8 (3.55 to 4.80)

Statistical Analysis 1 for Time from randomisation to study treatment discontinuation or death (TDT)

Groups^[1]	All groups
Method^[3]	Other [Log-rank test]
P-Value^[4]	0.0001
Hazard Ratio (HR)^[5]	0.446
95% Confidence Interval	( 0.297 to 0.670 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

7. Secondary Outcome Measure: Number of participants with objective response rate (ORR) by BICR using modified RECIST 1.1 [ Time Frame: Up to 4 years ]

Measure Type	Secondary
Measure Name	Number of participants with objective response rate (ORR) by BICR using modified RECIST 1.1
Measure Description	To determine efficacy by assessment of objective response rate according to modified RECIST 1.1 of olaparib maintenance monotherapy compared to placebo. The ORR is defined as the number of with a BoR of CR and PR according to the BICR data divided by the number of patients in the treatment group with measurable disease at baseline.
Time Frame	Up to 4 years
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomised patients with measurable disease at baseline.

Reporting Groups

	Description
Olaparib 300 mg twice daily (bd)	Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
Placebo	Randomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

	Olaparib 300 mg twice daily (bd)	Placebo
Number of Participants Analyzed [units:participants]	78	52
Number of participants with objective response rate (ORR) by BICR using modified RECIST 1.1 [units: Participants]	18	6

Statistical Analysis 1 for Number of participants with objective response rate (ORR) by BICR using modified RECIST 1.1

Groups^[1]	All groups
Method^[3]	Regression, Logistic
P-Value^[4]	0.1028
Odds Ratio (OR)^[5]	2.300
95% Confidence Interval	( 0.886 to 6.761 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

8. Secondary Outcome Measure: Disease control rate (DCR) by BICR using modified RECIST 1.1 [ Time Frame: At 16 weeks ]

Measure Type	Secondary
Measure Name	Disease control rate (DCR) by BICR using modified RECIST 1.1
Measure Description	Efficacy by assessment of disease control rate according to modified RECIST 1.1 of olaparib maintenance monotherapy compared to placebo.
Time Frame	At 16 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat (ITT): All randomised patients

Reporting Groups

	Description
Olaparib 300 mg twice daily (bd)	Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
Placebo	Randomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

	Olaparib 300 mg twice daily (bd)	Placebo
Number of Participants Analyzed [units:participants]	92	62
Disease control rate (DCR) by BICR using modified RECIST 1.1 [units: Participants]
Yes	49	23
Yes	41	35
Yes	2	4

No statistical analysis provided for Disease control rate (DCR) by BICR using modified RECIST 1.1

9. Secondary Outcome Measure: Adjusted mean change from baseline up to 6 months in global quality of life (QoL) score from the EORTC-QLQ-C30 questionnaire [ Time Frame: From baseline up to 6 months ]

Measure Type	Secondary
Measure Name	Adjusted mean change from baseline up to 6 months in global quality of life (QoL) score from the EORTC-QLQ-C30 questionnaire
Measure Description	To assess the effect of olaparib on health-related quality of life (QoL) as measured by the EORTC-QLQ-C30 global QoL scale. The EORTC-QLQ-C30 is defined as EORTC QLQ-C30: a questionnaire (30 questions) used to evaluate disease symptoms, functional impacts (eg, physical functioning), and HRQoL and to characterize clinical benefit from the patient perspective. The HRQoL score ranges from 0 to 100. A higher score indicates better QoL. A score change of 10 points was pre-defined as clinically meaningful. bd twice daily.
Time Frame	From baseline up to 6 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Patient reported outcome (PRO) analysis set was defined as the analysis population for PRO data were a subset of the FAS (ITT) population who had evaluable baseline EORTC QLQ-C30 or QLQ-PAN26 forms where evaluable meant that at least 1 sub-scale baseline score could be determined from at least 1 of the 2 forms.

Reporting Groups

	Description
Olaparib 300 mg twice daily (bd)	Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
Placebo	Randomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

	Olaparib 300 mg twice daily (bd)	Placebo
Number of Participants Analyzed [units:participants]	89	58
Adjusted mean change from baseline up to 6 months in global quality of life (QoL) score from the EORTC-QLQ-C30 questionnaire [units: Unit on scale] Mean (95% Confidence Interval)	-1.20 (-4.014 to 1.618)	1.27 (-2.580 to 5.124)

Statistical Analysis 1 for Adjusted mean change from baseline up to 6 months in global quality of life (QoL) score from the EORTC-QLQ-C30 questionnaire

Groups^[1]	All groups
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.310
Mean Difference (Final Values)^[5]	-2.47
95% Confidence Interval	( -7.267 to 2.327 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

10. Secondary Outcome Measure: Number of participants with adverse events (AEs) [ Time Frame: Up to 4 years ]

Measure Type	Secondary
Measure Name	Number of participants with adverse events (AEs)
Measure Description	To assess the safety and tolerability of olaparib maintenance monotherapy. SAE: serious adverse events CTCAE: Common Terminology Criteria for Adverse Events
Time Frame	Up to 4 years
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Olaparib 300 mg twice daily (bd)	Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
Placebo	Randomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

	Olaparib 300 mg twice daily (bd)	Placebo
Number of Participants Analyzed [units:participants]	91	60
Number of participants with adverse events (AEs) [units: Participants]
Any AE	87	56
Any AE	36	14
Any AE	0	0
Any AE	22	9
Any AE	5	1
Any AE	32	3
Any AE	15	2

No statistical analysis provided for Number of participants with adverse events (AEs)

Serious Adverse Events

Time Frame	From informed consent until 30 days after last dose + subsequent treatment-related events reported (maximum up to 4 years).
Additional Description	No text entered.

Reporting Groups

	Description
Olaparib 300 mg twice daily (bd)	Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
Placebo	Randomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Serious Adverse Events

Olaparib 300 mg twice daily (bd)

Placebo

Total, serious adverse events

# participants affected / at risk

22/91 (24.18%)

9/60 (15.00%)

Infections and infestations

Abdominal infection¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Infections and infestations

Bartholinitis¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Infections and infestations

Pneumonia¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Infections and infestations

Urinary tract infection¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Blood and lymphatic system disorders

Anaemia¹

# participants affected / at risk

6/91 (6.59%)

0/60 (0.00%)

Blood and lymphatic system disorders

Febrile Neutropenia¹

# participants affected / at risk

0/91 (0.00%)

1/60 (1.67%)

Endocrine disorders

Hypothyroidism¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Metabolism and nutrition disorders

Decreased appetite¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Metabolism and nutrition disorders

Hyperglycaemia¹

# participants affected / at risk

0/91 (0.00%)

1/60 (1.67%)

Nervous system disorders

Cerebrovascular accident¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Nervous system disorders

Embolic stroke¹

# participants affected / at risk

0/91 (0.00%)

1/60 (1.67%)

Nervous system disorders

Transient ischaemic attack¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Cardiac disorders

Cardiac failure¹

# participants affected / at risk

1/91 (1.10%)

1/60 (1.67%)

Vascular disorders

Vascular stenosis¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Respiratory, thoracic and mediastinal disorders

Pleural effusion¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Respiratory, thoracic and mediastinal disorders

Pneumothorax¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Gastrointestinal disorders

Abdominal pain¹

# participants affected / at risk

3/91 (3.30%)

1/60 (1.67%)

Gastrointestinal disorders

Constipation¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Gastrointestinal disorders

Duodenal perforation¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Gastrointestinal disorders

Gastric varices haemorrhage¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Gastrointestinal disorders

Incarcerated inguinal hernia¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Gastrointestinal disorders

Large intestinal obstruction¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Gastrointestinal disorders

Melaena¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Gastrointestinal disorders

Obstruction gastric¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Gastrointestinal disorders

Pancreatitis¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Gastrointestinal disorders

Vomiting¹

# participants affected / at risk

1/91 (1.10%)

3/60 (5.00%)

Hepatobiliary disorders

Bile duct obstruction¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Hepatobiliary disorders

Cholangitis¹

# participants affected / at risk

2/91 (2.20%)

1/60 (1.67%)

Hepatobiliary disorders

Cholecystitis¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

General disorders

General physical health deterioration¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Investigations

Platelet count decreased¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Injury, poisoning and procedural complications

Anastomotic haemorrhage¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Product Issues

Device occlusion¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Product Issues

Stent malfunction¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

General disorders

Pyrexia¹

# participants affected / at risk

0/91 (0.00%)

2/60 (3.33%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA version 21.1

Other Adverse Events

Time Frame	From informed consent until 30 days after last dose + subsequent treatment-related events reported (maximum up to 4 years).
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Olaparib 300 mg twice daily (bd)	Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
Placebo	Randomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Other Adverse Events

Olaparib 300 mg twice daily (bd)

Placebo

Total, other (not including serious) adverse events

# participants affected / at risk

87/91 (95.60%)

56/60 (93.33%)

Gastrointestinal disorders

Nausea¹

# participants affected / at risk

41/91 (45.05%)

14/60 (23.33%)

Gastrointestinal disorders

Diarrhoea¹

# participants affected / at risk

26/91 (28.57%)

9/60 (15.00%)

Gastrointestinal disorders

Abdominal pain¹

# participants affected / at risk

23/91 (25.27%)

14/60 (23.33%)

Gastrointestinal disorders

Constipation¹

# participants affected / at risk

20/91 (21.98%)

6/60 (10.00%)

Gastrointestinal disorders

Vomiting¹

# participants affected / at risk

18/91 (19.78%)

8/60 (13.33%)

Gastrointestinal disorders

Stomatitis¹

# participants affected / at risk

7/91 (7.69%)

3/60 (5.00%)

Gastrointestinal disorders

Abdominal pain upper¹

# participants affected / at risk

6/91 (6.59%)

8/60 (13.33%)

Gastrointestinal disorders

Dry mouth¹

# participants affected / at risk

6/91 (6.59%)

1/60 (1.67%)

Gastrointestinal disorders

Dyspepsia¹

# participants affected / at risk

5/91 (5.49%)

5/60 (8.33%)

Gastrointestinal disorders

Abdominal distension¹

# participants affected / at risk

4/91 (4.40%)

6/60 (10.00%)

Gastrointestinal disorders

Flatulence¹

# participants affected / at risk

2/91 (2.20%)

4/60 (6.67%)

General disorders

Fatigue¹

# participants affected / at risk

41/91 (45.05%)

16/60 (26.67%)

General disorders

Asthenia¹

# participants affected / at risk

15/91 (16.48%)

5/60 (8.33%)

General disorders

Pyrexia¹

# participants affected / at risk

12/91 (13.19%)

3/60 (5.00%)

General disorders

Oedema peripheral¹

# participants affected / at risk

8/91 (8.79%)

5/60 (8.33%)

Musculoskeletal and connective tissue disorders

Back pain¹

# participants affected / at risk

17/91 (18.68%)

10/60 (16.67%)

Musculoskeletal and connective tissue disorders

Arthralgia¹

# participants affected / at risk

14/91 (15.38%)

6/60 (10.00%)

Musculoskeletal and connective tissue disorders

Muscle spasms¹

# participants affected / at risk

6/91 (6.59%)

2/60 (3.33%)

Musculoskeletal and connective tissue disorders

Pain in extremity¹

# participants affected / at risk

6/91 (6.59%)

4/60 (6.67%)

Musculoskeletal and connective tissue disorders

Musculoskeletal pain¹

# participants affected / at risk

5/91 (5.49%)

3/60 (5.00%)

Musculoskeletal and connective tissue disorders

Myalgia¹

# participants affected / at risk

5/91 (5.49%)

3/60 (5.00%)

Musculoskeletal and connective tissue disorders

Flank pain¹

# participants affected / at risk

1/91 (1.10%)

4/60 (6.67%)

Nervous system disorders

Dysgeusia¹

# participants affected / at risk

10/91 (10.99%)

3/60 (5.00%)

Nervous system disorders

Neuropathy peripheral¹

# participants affected / at risk

7/91 (7.69%)

7/60 (11.67%)

Nervous system disorders

Dizziness¹

# participants affected / at risk

6/91 (6.59%)

3/60 (5.00%)

Nervous system disorders

Headache¹

# participants affected / at risk

6/91 (6.59%)

8/60 (13.33%)

Nervous system disorders

Peripheral sensory neuropathy¹

# participants affected / at risk

6/91 (6.59%)

2/60 (3.33%)

Blood and lymphatic system disorders

Anaemia¹

# participants affected / at risk

23/91 (25.27%)

10/60 (16.67%)

Blood and lymphatic system disorders

Neutropenia¹

# participants affected / at risk

7/91 (7.69%)

4/60 (6.67%)

Blood and lymphatic system disorders

Thrombocytopenia¹

# participants affected / at risk

7/91 (7.69%)

4/60 (6.67%)

Metabolism and nutrition disorders

Decreased appetite¹

# participants affected / at risk

22/91 (24.18%)

4/60 (6.67%)

Metabolism and nutrition disorders

Hyperglycaemia¹

# participants affected / at risk

8/91 (8.79%)

1/60 (1.67%)

Skin and subcutaneous tissue disorders

Rash¹

# participants affected / at risk

11/91 (12.09%)

2/60 (3.33%)

Skin and subcutaneous tissue disorders

Pruritus¹

# participants affected / at risk

9/91 (9.89%)

4/60 (6.67%)

Investigations

Alanine aminotransferase increased¹

# participants affected / at risk

8/91 (8.79%)

1/60 (1.67%)

Investigations

Aspartate aminotransferase increased¹

# participants affected / at risk

6/91 (6.59%)

1/60 (1.67%)

Investigations

Blood creatinine increased¹

# participants affected / at risk

6/91 (6.59%)

1/60 (1.67%)

Investigations

Blood alkaline phosphatase increased¹

# participants affected / at risk

5/91 (5.49%)

3/60 (5.00%)

Investigations

Platelet count decreased¹

# participants affected / at risk

5/91 (5.49%)

0/60 (0.00%)

Psychiatric disorders

Insomnia¹

# participants affected / at risk

7/91 (7.69%)

1/60 (1.67%)

Psychiatric disorders

Anxiety¹

# participants affected / at risk

5/91 (5.49%)

2/60 (3.33%)

Psychiatric disorders

Depression¹

# participants affected / at risk

5/91 (5.49%)

0/60 (0.00%)

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹

# participants affected / at risk

10/91 (10.99%)

3/60 (5.00%)

Respiratory, thoracic and mediastinal disorders

Cough¹

# participants affected / at risk

8/91 (8.79%)

2/60 (3.33%)

Infections and infestations

Nasopharyngitis¹

# participants affected / at risk

11/91 (12.09%)

2/60 (3.33%)

Infections and infestations

Influenza¹

# participants affected / at risk

5/91 (5.49%)

0/60 (0.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA version 21.1

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: This submission /document contains trade secrets and confidential commercial information, disclosure of which is prohibited without providing advance notice to AstraZeneca and opportunity to object.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Global Clinical Leader
Organization:	AstraZeneca AB
Phone	1-877-240-9479
E-mail:	information.center@astrazeneca.com

.

Purpose

A Phase III, Randomised, Double Blind, Placebo Controlled, Multicentre
Study of Maintenance Olaparib Monotherapy in Patients with gBRCA
Mutated Metastatic Pancreatic Cancer whose Disease Has Not Progressed on
First Line Platinum Based Chemotherapy

Official Title:	A Phase III, Randomised, Double Blind, Placebo Controlled, Multicentre Study of Maintenance Olaparib Monotherapy in Patients with gBRCA Mutated Metastatic Pancreatic Cancer whose Disease Has Not Progressed on First Line Platinum Based Chemotherapy
Study Type:	Interventional
Overall Recruitment Status:	Active, not recruiting
Study Start Date:	16 December 2014
Study Start Date Type:	Actual
Primary Completion Date:	15 January 2019
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment

Condition	Intervention	Phase
germline BRCA1/2 mutations and metastatic adenocarcinoma of the pancreas	Drug: Olaparib Drug: Olaparib Drug: Placebo Drug: Placebo	Phase 3

Ages Eligible for Study:	18 Years to 130 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:
-Histologically or cytologically confirmed pancreas adenocarcinoma receiving initial chemotherapy for metastatic disease and without evidence of disease progression on treatment
-Patients with measurable disease and/or non-measurable or no evidence of disease
assessed at baseline by CT (or MRI where CT is contraindicated) will be entered in
this study.
-Documented mutation in gBRCA1 or gBRCA2 that is predicted to be deleterious or
suspected deleterious
- Patients are on treatment with a first line platinum-based (cisplatin, carboplatin or
oxaliplatin) regimen for metastatic pancreas cancer, have received a minimum of 16
weeks of continuous platinum treatment and have no evidence of progression based
on investigator’s opinion.
-Patients who have received platinum as potentially curative treatment for a prior
cancer (eg ovarian cancer) or as adjuvant/neoadjuvant treatment for pancreas cancer
are eligible provided at least 12 months have elapsed between the last dose of
platinum-based treatment and initiation of the platinum-based chemotherapy for
metastatic pancreas cancer.

Major Exclusion Criteria:
-gBRCA1 and/or gBRCA2 mutations that are considered to be non detrimental (eg,
“Variants of uncertain clinical significance” or “Variant of unknown significance”
or “Variant, favour polymorphism” or “benign polymorphism” etc.)
-Progression of tumour between start of first line platinum based chemotherapy for
metastatic pancreas cancer and randomisation.
-Cytotoxic chemotherapy or non-hormonal targeted therapy within 28 days of Cycle
1 Day 1 is not permitted.
-Exposure to an investigational product within 30 days or 5 half lives (whichever is
longer) prior to randomisation
-Any previous treatment with a PARP inhibitor, including Olaparib

Contacts

Contact: AstraZeneca Clinical Study Information Center	1-877-240-9479	information.center@astrazeneca.com
Contact Backup: AstraZeneca Cancer Study Locator Service	1-877-400-4656	astrazeneca@emergingmed.com

Sponsors and Collaborators

AstraZeneca

Myriad Genetics - BRCAnalysis test for FDA Premarket Approval (PMA)

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Locations

Country	Location	Facility	Status
Belgium	Research Site	Antwerpen, Belgium, 2020	Completed
Belgium	Research Site	Brussels (Anderlecht), Belgium, 1070	Completed
Belgium	Research Site	Edegem, Belgium, 2650	Withdrawn
Belgium	Research Site	Leuven, Belgium, 3000	Active, not recruiting
Canada	Research Site	Toronto, Canada, M5G 2M9	Completed
Germany	Research Site	Berlin, Germany, 10967	Active, not recruiting
Germany	Research Site	Berlin, Germany, D-13353	Completed
Germany	Research Site	Bochum, Germany, 44791	Active, not recruiting
Germany	Research Site	Bonn, Germany, 53127	Completed
Germany	Research Site	Dresden, Germany, 01307	Completed
Germany	Research Site	Frankfurt am Main, Germany, 60596	Completed
Germany	Research Site	Freiburg im Breisgau, Germany, 79106	Withdrawn
Germany	Research Site	Hamburg, Germany, 22291	Completed
Germany	Research Site	Hamburg, Germany, 20246	Completed
Germany	Research Site	Hannover, Germany, 30625	Completed
Germany	Research Site	Leipzig, Germany, 04103	Completed
Germany	Research Site	München, Germany, 81675	Active, not recruiting
Germany	Research Site	Schweinfurt, Germany, 97422	Completed
Germany	Research Site	Ulm, Germany, 89081	Completed
Australia	Research Site	Campbelltown, Australia, 2560	Completed
Australia	Research Site	Lilydale, Australia, 3140	Withdrawn
Australia	Research Site	Randwick, Australia, 2031	Active, not recruiting
Australia	Research Site	St Leonards, Australia, 2065	Completed
Australia	Research Site	Woolloongabba, Australia, 4102	Withdrawn
Canada , ON	Research Site	London, ON, Canada, N6A 4L6	Completed
Canada , ON	Research Site	Ottawa, ON, Canada, K1H 8L6	Withdrawn
France	Research Site	Amiens, France, 80054	Completed
France	Research Site	Besançon, France, 25030	Completed
France	Research Site	Bordeaux, France, 33075	Active, not recruiting
France	Research Site	Brest Cedex, France, 29609	Completed
France	Research Site	Clichy Cedex, France, 92118	Active, not recruiting
France	Research Site	La Roche sur Yon, France, 85925	Completed
France	Research Site	LILLE, France, 59020	Active, not recruiting
France	Research Site	Lyon, France, 69008	Withdrawn
France	Research Site	LYON CEDEX 03, France, 69437	Active, not recruiting
France	Research Site	Montpellier, France, 34298	Withdrawn
France	Research Site	Nice, France, 06189	Completed
France	Research Site	PARIS, France, 75014	Completed
France	Research Site	Paris CEDEX 14, France, 75674	Completed
France	Research Site	POITIERS, France, 86021	Active, not recruiting
France	Research Site	Rennes, France, 35042	Withdrawn
France	Research Site	STRASBOURG Cedex, France, 67065	Completed
France	Research Site	Toulouse, France, 31059	Completed
France	Research Site	Villejuif, France, 94800	Completed
Israel	Research Site	Beer Sheva, Israel, 84101	Completed
Israel	Research Site	Haifa, Israel, 3109601	Completed
Israel	Research Site	Holon, Israel, 58100	Completed
Israel	Research Site	Nahariya, Israel, 22100	Active, not recruiting
Israel	Research Site	Petah Tikva, Israel, 4941492	Active, not recruiting
Israel	Research Site	Ramat Gan, Israel, 5265601	Active, not recruiting
Israel	Research Site	Rehovot, Israel, 76100	Completed
Israel	Research Site	Tel Aviv, Israel, 6423906	Active, not recruiting
Israel	Research Site	Zefir, Israel, 7030000	Completed
Spain	Research Site	Barcelona, Spain, 08035	Completed
Spain	Research Site	Girona, Spain, 17007	Active, not recruiting
Spain	Research Site	L'Hospitalet de Llobregat, Spain, 08907	Completed
Spain	Research Site	Madrid, Spain, 28007	Completed
Spain	Research Site	Madrid, Spain, 28034	Completed
Spain	Research Site	Madrid, Spain, 28050	Completed
Spain	Research Site	Madrid, Spain, 28041	Active, not recruiting
Spain	Research Site	Málaga, Spain, 29010	Completed
Spain	Research Site	Pamplona, Spain, 31008	Completed
Spain	Research Site	Sabadell, Spain, 8208	Completed
Spain	Research Site	Santiago de Compostela, Spain, 15706	Completed
Spain	Research Site	Valencia, Spain, 46009	Completed
Spain	Research Site	Zaragoza, Spain, 50009	Completed
United Kingdom	Research Site	Edinburgh, United Kingdom, EH4 2XR	Completed
United Kingdom	Research Site	Glasgow, United Kingdom, G12 0YN	Completed
United Kingdom	Research Site	Leeds, United Kingdom, LS9 7TF	Withdrawn
United Kingdom	Research Site	Liverpool, United Kingdom, L69 3GA	Active, not recruiting
United Kingdom	Research Site	London, United Kingdom, WC1E 6AG	Completed
United Kingdom	Research Site	London, United Kingdom, SE5 9RS	Completed
United Kingdom	Research Site	Manchester, United Kingdom, M20 4BX	Completed
United Kingdom	Research Site	Northwood, United Kingdom, HA6 2RN	Completed
United Kingdom	Research Site	Nottingham, United Kingdom, NG5 1PB	Completed
United Kingdom	Research Site	Surrey, United Kingdom, SM1 2DL	Active, not recruiting
South Korea	Research Site	Seongnam-si, South Korea, 13620	Completed
South Korea	Research Site	Seoul, South Korea, 03080	Active, not recruiting
South Korea	Research Site	Seoul, South Korea, 6351	Active, not recruiting
Netherlands	Research Site	Amsterdam, Netherlands, 1105 AZ	Active, not recruiting
Netherlands	Research Site	Maastricht, Netherlands, 6202 AZ	Withdrawn
United States of America , CA	Research Site	Downey, CA, United States of America, 90241	Withdrawn
United States of America , CA	Research Site	La Jolla, CA, United States of America, 92093	Withdrawn
United States of America , CA	Research Site	Los Angeles, CA, United States of America, 90048	Withdrawn
United States of America , CA	Research Site	Los Angeles, CA, United States of America, 90030	Withdrawn
United States of America , CA	Research Site	Santa Monica, CA, United States of America, 90404	Withdrawn
United States of America , CA	Research Site	Stanford, CA, United States of America, 94305-5720	Active, not recruiting
Canada , QC	Research Site	Montreal, QC, Canada, H2X 3J4	Withdrawn
Canada , QC	Research Site	Sherbrooke, QC, Canada, J1G 2E8	Completed
Italy	Research Site	Ancona, Italy, 60126	Withdrawn
Italy	Research Site	Bologna, Italy, 40138	Completed
Italy	Research Site	Milano, Italy, 20132	Active, not recruiting
Italy	Research Site	Milano, Italy, 20133	Completed
Italy	Research Site	Monserrato, Italy, 09042	Withdrawn
Italy	Research Site	PADOVA, Italy, 35128	Completed
Italy	Research Site	Parma, Italy, 43126	Completed
Italy	Research Site	Pescara, Italy, 65100	Completed
Italy	Research Site	Pisa, Italy, 56126	Withdrawn
Italy	Research Site	Roma, Italy, 00144	Completed
Italy	Research Site	Roma, Italy, 00128	Completed
Italy	Research Site	San Giovanni Rotondo, Italy, 71013	Completed
Italy	Research Site	Verona, Italy, 37134	Active, not recruiting
United States of America , IL	Research Site	Chicago, IL, United States of America, 60637	Completed
United States of America , IL	Research Site	Evanston, IL, United States of America, 60201	Withdrawn
United States of America , MD	Research Site	Baltimore, MD, United States of America, 21287	Active, not recruiting
United States of America , MD	Research Site	Bethesda, MD, United States of America, 20889	Withdrawn
United States of America , PA	Research Site	Philadelphia, PA, United States of America, 19111	Completed
United States of America , Connecticut	Research Site	New Haven, Connecticut, United States of America, 06510-3220	Completed
United States of America , OH	Research Site	Columbus, OH, United States of America, 43210	Completed
United States of America , CO	Research Site	Aurora, CO, United States of America, 80045	Completed
United States of America , FL	Research Site	Boca Raton, FL, United States of America, 33486	Active, not recruiting
United States of America , FL	Research Site	Miami, FL, United States of America, 33136	Withdrawn
United States of America , FL	Research Site	Miami, FL, United States of America, 33136	Active, not recruiting
United States of America , NY	Research Site	Commack, NY, United States of America, 11725	Completed
United States of America , NY	Research Site	New York, NY, United States of America, 10032	Completed
United States of America , NY	Research Site	New York, NY, United States of America, 10022	Completed
United States of America , NY	Research Site	New York, NY, United States of America, 10065	Completed
United States of America , NY	Research Site	Sleepy Hollow, NY, United States of America, 10591	Withdrawn
United States of America , NY	Research Site	West Harrison, NY, United States of America, 10604	Withdrawn
United States of America , MO	Research Site	St Louis, MO, United States of America, 63110	Completed
United States of America , SC	Research Site	Spartenburg, SC, United States of America, 29303	Withdrawn
Canada , Quebec	Research Site	Montreal, Quebec, Canada, H3T 1E2	Completed
United States of America , Arizona	Research Site	Gilbert, Arizona, United States of America, 85234	Completed
United States of America , California	Research Site	Orange, California, United States of America, 92868-3298	Completed
United States of America , MA	Research Site	Boston, MA, United States of America, 02114-2696	Withdrawn
United States of America , MA	Research Site	Boston, MA, United States of America, 02215	Active, not recruiting
United States of America , WA	Research Site	Seattle, WA, United States of America, 98109	Withdrawn
United States of America , WA	Research Site	Seattle, WA, United States of America, 98104	Completed
Canada , MB	Research Site	Winnipeg, MB, Canada, R2H 2A6	Withdrawn
United States of America , TX	Research Site	Arlington, TX, United States of America, 76012	Withdrawn
United States of America , TX	Research Site	Dallas, TX, United States of America, 75390	Withdrawn
United States of America , TX	Research Site	Houston, TX, United States of America, 77030	Active, not recruiting
United States of America , New York	Research Site	New York City, New York, United States of America, 10015	Completed
United States of America , New York	Research Site	Rockville Centre, New York, United States of America, 11570-1000	Withdrawn
United States of America , NJ	Research Site	Basking Ridge, NJ, United States of America, 07920	Withdrawn
United States of America , DC	Research Site	Washington, DC, United States of America, 20007	Withdrawn

Oversight

Is FDA regulated intervention:	Yes
Is IND/IDE protocol:	Yes
Section 801 trial:	Yes
Delayed Posting:	No
IND/IDE Grantor:	CDER
IND/IDE Number:	121412
Has Expanded Access:	No

More Information

https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&parentIdentifier=D081FC00001&attachmentIdentifier=9095e288-3d26-4c56-87dd-5dedc61f25c2&fileName=POLO_Revised_CSP_2-24Jul2019_Redacted.pdf&versionIdentifier=

Redacted_SAP

Publications:

Golan T, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algül H, O'Reilly EM, McGuinness D, Cui KY, Schlienger K, Locker GY, Kindler HL. Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer. N Engl J Med. 2019 Jul 25;381(4):317-327. doi: 10.1056/NEJMoa1903387. Epub 2019 Jun 2. PMID:31157963

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT02184195
Other Study ID Numbers:	D081FC00001, 2014-001589-85
Health Authority:	United States: Food and Drug Administration Australia: National Health and Medical Research Council France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Germany: Federal Institute for Drugs and Medical Devices United Kingdom: Medicines and Healthcare Products Regulatory Agency Canada: Canadian Institutes of Health Research Israel: Israeli Health Ministry Pharmaceutical Administration Spain: Spanish Agency of Medicines Belgium: Federal Agency for Medicinal Products and Health Products Korea: Food and Drug Administration

Keywords provided by AstraZeneca

BRCA, metastatic adenocarcinoma pancreas, maintenance olaparib monotherapy, first line platinum chemotherapy, pancreatic cancer, PARP inhibitor

Additional Relevant MeSH terms:

germline BRCA1/2 mutations and

metastatic adenocarcinoma of the pancreas

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study randomised patients at a total of 59 study centres in 12 countries: United States of America (13), Germany (8), France (7), Israel (7), Spain (7), United Kingdom (6), Italy (4), Belgium (2), Republic of Korea (2), Australia (1), Canada (1) and Netherlands (1).

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Screening Part 1 was only required if a patient’s gBRCAm status was unknown and Screening Part 2 was for patients with known local germline BRCA (gBRCA) test. All other screening parameters were done as per the Study Schedule.

Reporting Groups

	Description
Olaparib 300 mg twice daily (bd)	Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
Placebo	Randomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Participant Flow: Overall Study

	Olaparib 300 mg twice daily (bd)	Placebo
STARTED	92	62
COMPLETED	49	27
NOT COMPLETED	43	35
Patient decision	3	1
Eligibility criteria not fulfilled	0	1
Death	40	29
Lost to Follow-up	0	2
Other	0	2

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
Olaparib 300 mg twice daily (bd)	Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
Placebo	Randomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Baseline Measures

	Olaparib 300 mg twice daily (bd)	Placebo	Total
Number of Participants [units: Participants]	92	62	154
Age Continuous [units: Years] Mean ± Standard Deviation	58.2 ± 10.27	56.4 ± 9.07	57.5 ± 9.81
Sex: Female, Male [units: Participants]
Female	39	31	70
Male	53	31	84
Race (NIH/OMB) [units: Participants]
American Indian or Alaska Native	1	0	1
Asian	4	2	6
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	5	0	5
White	82	59	141
More than one race	0	0	0
Unknown or Not Reported	0	1	1
Ethnicity (NIH/OMB) [units: Participants]
Hispanic or Latino	4	2	6
Not Hispanic or Latino	88	60	148
Unknown or Not Reported	0	0	0

Outcome Measures

1. Primary Outcome Measure: Progression-free survival (PFS) by blinded independent central review (BICR) using modified Response Evaluation Criteria in Solid Tumours. This study used modified RECIST version (v) 1.1 (RECIST v1.1) [ Time Frame: Up to 4 years ]

Measure Type	Primary
Measure Name	Progression-free survival (PFS) by blinded independent central review (BICR) using modified Response Evaluation Criteria in Solid Tumours. This study used modified RECIST version (v) 1.1 (RECIST v1.1)
Measure Description	To determine the efficacy of olaparib maintenance monotherapy compared to placebo by PFS. The PFS was defined as the time from randomisation until the date of objective radiological disease progression according to modified RECIST v1.1 or death (by any cause in the absence of disease progression) regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to disease progression.
Time Frame	Up to 4 years
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat (ITT): All randomised patients, Myriad confirmed Breast cancer susceptibility gene mutation (gBRCAm) subgroup.

Reporting Groups

	Description
Olaparib 300 mg twice daily (bd)	Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
Placebo	Randomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

	Olaparib 300 mg twice daily (bd)	Placebo
Number of Participants Analyzed [units:participants]	92	62
Progression-free survival (PFS) by blinded independent central review (BICR) using modified Response Evaluation Criteria in Solid Tumours. This study used modified RECIST version (v) 1.1 (RECIST v1.1) [units: Months] Median (95% Confidence Interval)	7.4 (4.14 to 11.01)	3.8 (3.52 to 4.86)

Statistical Analysis 1 for Progression-free survival (PFS) by blinded independent central review (BICR) using modified Response Evaluation Criteria in Solid Tumours. This study used modified RECIST version (v) 1.1 (RECIST v1.1)

Groups^[1]	All groups
Method^[3]	Other [Log-rank test]
P-Value^[4]	0.0038
Hazard Ratio (HR)^[5]	0.531
95% Confidence Interval	( 0.346 to 0.815 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

2. Secondary Outcome Measure: Overall Survival (OS) [ Time Frame: Upto 4 years ]

Measure Type	Secondary
Measure Name	Overall Survival (OS)
Measure Description	To determine the efficacy by assessment of OS of olaparib maintenance monotherapy compared to placebo. The OS was defined as the time from the date of randomization until death due to any cause.
Time Frame	Upto 4 years
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat (ITT): All randomised patients, Myriad confirmed Breast cancer susceptibility gene mutation (gBRCAm) subgroup.

Reporting Groups

	Description
Olaparib 300 mg twice daily (bd)	Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
Placebo	Randomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

	Olaparib 300 mg twice daily (bd)	Placebo
Number of Participants Analyzed [units:participants]	92	62
Overall Survival (OS) [units: Months] Median (95% Confidence Interval)	18.9 (14.85 to 26.15)	18.1 (12.62 to 26.12)

Statistical Analysis 1 for Overall Survival (OS)

Groups^[1]	All groups
Method^[3]	Other [Log-rank test]
P-Value^[4]	0.6833
Hazard Ratio (HR)^[5]	0.906
95% Confidence Interval	( 0.563 to 1.457 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

3. Secondary Outcome Measure: Time from randomisation to second progression (PFS2) [ Time Frame: Up to 4 years ]

Measure Type	Secondary
Measure Name	Time from randomisation to second progression (PFS2)
Measure Description	To determine efficacy by assessment of PFS2 of olaparib maintenance monotherapy compared to placebo. The PFS2 was defined as the time from the date of randomisation to the earliest of the progression event subsequent to that used for the primary variable PFS or death.
Time Frame	Up to 4 years
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat (ITT): All randomised patients, Myriad confirmed Breast cancer susceptibility gene mutation (gBRCAm) subgroup.

Reporting Groups

	Description
Olaparib 300 mg twice daily (bd)	Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
Placebo	Randomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

	Olaparib 300 mg twice daily (bd)	Placebo
Number of Participants Analyzed [units:participants]	92	62
Time from randomisation to second progression (PFS2) [units: Months] Median (95% Confidence Interval)	13.2 (7.75 to 26.15)	9.2 (7.62 to 13.54)

Statistical Analysis 1 for Time from randomisation to second progression (PFS2)

Groups^[1]	All groups
Method^[3]	Other [Log-rank test]
P-Value^[4]	0.2597
Hazard Ratio (HR)^[5]	0.755
95% Confidence Interval	( 0.464 to 1.230 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

4. Secondary Outcome Measure: Time from randomisation to second subsequent therapy or death (TSST) [ Time Frame: Up to 4 years ]

Measure Type	Secondary
Measure Name	Time from randomisation to second subsequent therapy or death (TSST)
Measure Description	To determine the efficacy by assessment of TSST of olaparib maintenance monotherapy compared to placebo. The TSST was defined as time to second subsequent therapy or death.
Time Frame	Up to 4 years
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat (ITT): All randomised patients, Myriad confirmed Breast cancer susceptibility gene mutation (gBRCAm) subgroup.

Reporting Groups

	Description
Olaparib 300 mg twice daily (bd)	Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
Placebo	Randomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

	Olaparib 300 mg twice daily (bd)	Placebo
Number of Participants Analyzed [units:participants]	92	62
Time from randomisation to second subsequent therapy or death (TSST) [units: Months] Median (95% Confidence Interval)	13.2 (8.84 to 20.04)	9.2 (8.34 to 13.14)

Statistical Analysis 1 for Time from randomisation to second subsequent therapy or death (TSST)

Groups^[1]	All groups
Method^[3]	Other [Log-rank test]
P-Value^[4]	0.0825
Hazard Ratio (HR)^[5]	0.678
95% Confidence Interval	( 0.437 to 1.051 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

5. Secondary Outcome Measure: Time from randomisation to first subsequent therapy or death (TFST) [ Time Frame: Up to 4 years ]

Measure Type	Secondary
Measure Name	Time from randomisation to first subsequent therapy or death (TFST)
Measure Description	To determine the efficacy by assessment of TFST of olaparib maintenance monotherapy compared to placebo. The TFST was defined as time to first subsequent therapy or death.
Time Frame	Up to 4 years
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat (ITT): All randomised patients, Myriad confirmed Breast cancer susceptibility gene mutation (gBRCAm) subgroup.

Reporting Groups

	Description
Olaparib 300 mg twice daily (bd)	Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
Placebo	Randomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

	Olaparib 300 mg twice daily (bd)	Placebo
Number of Participants Analyzed [units:participants]	92	62
Time from randomisation to first subsequent therapy or death (TFST) [units: Months] Median (95% Confidence Interval)	8.6 (6.21 to 12.45)	5.7 (4.17 to 6.34)

Statistical Analysis 1 for Time from randomisation to first subsequent therapy or death (TFST)

Groups^[1]	All groups
Method^[3]	Other [Log-rank test]
P-Value^[4]	0.0013
Hazard Ratio (HR)^[5]	0.496
95% Confidence Interval	( 0.324 to 0.760 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

6. Secondary Outcome Measure: Time from randomisation to study treatment discontinuation or death (TDT) [ Time Frame: Up to 4 years ]

Measure Type	Secondary
Measure Name	Time from randomisation to study treatment discontinuation or death (TDT)
Measure Description	To determine the efficacy by assessment of TDT compared to placebo. compared to placebo. The TDT was defined as time to study treatment discontinuation or death.
Time Frame	Up to 4 years
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat (ITT): All randomised patients, Myriad confirmed Breast cancer susceptibility gene mutation (gBRCAm) subgroup.

Reporting Groups

	Description
Olaparib 300 mg twice daily (bd)	Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
Placebo	Randomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

	Olaparib 300 mg twice daily (bd)	Placebo
Number of Participants Analyzed [units:participants]	92	62
Time from randomisation to study treatment discontinuation or death (TDT) [units: Months] Median (95% Confidence Interval)	7.2 (5.52 to 10.84)	3.8 (3.55 to 4.80)

Statistical Analysis 1 for Time from randomisation to study treatment discontinuation or death (TDT)

Groups^[1]	All groups
Method^[3]	Other [Log-rank test]
P-Value^[4]	0.0001
Hazard Ratio (HR)^[5]	0.446
95% Confidence Interval	( 0.297 to 0.670 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

7. Secondary Outcome Measure: Number of participants with objective response rate (ORR) by BICR using modified RECIST 1.1 [ Time Frame: Up to 4 years ]

Measure Type	Secondary
Measure Name	Number of participants with objective response rate (ORR) by BICR using modified RECIST 1.1
Measure Description	To determine efficacy by assessment of objective response rate according to modified RECIST 1.1 of olaparib maintenance monotherapy compared to placebo. The ORR is defined as the number of with a BoR of CR and PR according to the BICR data divided by the number of patients in the treatment group with measurable disease at baseline.
Time Frame	Up to 4 years
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomised patients with measurable disease at baseline.

Reporting Groups

	Description
Olaparib 300 mg twice daily (bd)	Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
Placebo	Randomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

	Olaparib 300 mg twice daily (bd)	Placebo
Number of Participants Analyzed [units:participants]	78	52
Number of participants with objective response rate (ORR) by BICR using modified RECIST 1.1 [units: Participants]	18	6

Statistical Analysis 1 for Number of participants with objective response rate (ORR) by BICR using modified RECIST 1.1

Groups^[1]	All groups
Method^[3]	Regression, Logistic
P-Value^[4]	0.1028
Odds Ratio (OR)^[5]	2.300
95% Confidence Interval	( 0.886 to 6.761 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

8. Secondary Outcome Measure: Disease control rate (DCR) by BICR using modified RECIST 1.1 [ Time Frame: At 16 weeks ]

Measure Type	Secondary
Measure Name	Disease control rate (DCR) by BICR using modified RECIST 1.1
Measure Description	Efficacy by assessment of disease control rate according to modified RECIST 1.1 of olaparib maintenance monotherapy compared to placebo.
Time Frame	At 16 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to treat (ITT): All randomised patients

Reporting Groups

	Description
Olaparib 300 mg twice daily (bd)	Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
Placebo	Randomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

	Olaparib 300 mg twice daily (bd)	Placebo
Number of Participants Analyzed [units:participants]	92	62
Disease control rate (DCR) by BICR using modified RECIST 1.1 [units: Participants]
Yes	49	23
Yes	41	35
Yes	2	4

No statistical analysis provided for Disease control rate (DCR) by BICR using modified RECIST 1.1

9. Secondary Outcome Measure: Adjusted mean change from baseline up to 6 months in global quality of life (QoL) score from the EORTC-QLQ-C30 questionnaire [ Time Frame: From baseline up to 6 months ]

Measure Type	Secondary
Measure Name	Adjusted mean change from baseline up to 6 months in global quality of life (QoL) score from the EORTC-QLQ-C30 questionnaire
Measure Description	To assess the effect of olaparib on health-related quality of life (QoL) as measured by the EORTC-QLQ-C30 global QoL scale. The EORTC-QLQ-C30 is defined as EORTC QLQ-C30: a questionnaire (30 questions) used to evaluate disease symptoms, functional impacts (eg, physical functioning), and HRQoL and to characterize clinical benefit from the patient perspective. The HRQoL score ranges from 0 to 100. A higher score indicates better QoL. A score change of 10 points was pre-defined as clinically meaningful. bd twice daily.
Time Frame	From baseline up to 6 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Patient reported outcome (PRO) analysis set was defined as the analysis population for PRO data were a subset of the FAS (ITT) population who had evaluable baseline EORTC QLQ-C30 or QLQ-PAN26 forms where evaluable meant that at least 1 sub-scale baseline score could be determined from at least 1 of the 2 forms.

Reporting Groups

	Description
Olaparib 300 mg twice daily (bd)	Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
Placebo	Randomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

	Olaparib 300 mg twice daily (bd)	Placebo
Number of Participants Analyzed [units:participants]	89	58
Adjusted mean change from baseline up to 6 months in global quality of life (QoL) score from the EORTC-QLQ-C30 questionnaire [units: Unit on scale] Mean (95% Confidence Interval)	-1.20 (-4.014 to 1.618)	1.27 (-2.580 to 5.124)

Statistical Analysis 1 for Adjusted mean change from baseline up to 6 months in global quality of life (QoL) score from the EORTC-QLQ-C30 questionnaire

Groups^[1]	All groups
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.310
Mean Difference (Final Values)^[5]	-2.47
95% Confidence Interval	( -7.267 to 2.327 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

10. Secondary Outcome Measure: Number of participants with adverse events (AEs) [ Time Frame: Up to 4 years ]

Measure Type	Secondary
Measure Name	Number of participants with adverse events (AEs)
Measure Description	To assess the safety and tolerability of olaparib maintenance monotherapy. SAE: serious adverse events CTCAE: Common Terminology Criteria for Adverse Events
Time Frame	Up to 4 years
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Olaparib 300 mg twice daily (bd)	Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
Placebo	Randomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Measured Values

	Olaparib 300 mg twice daily (bd)	Placebo
Number of Participants Analyzed [units:participants]	91	60
Number of participants with adverse events (AEs) [units: Participants]
Any AE	87	56
Any AE	36	14
Any AE	0	0
Any AE	22	9
Any AE	5	1
Any AE	32	3
Any AE	15	2

No statistical analysis provided for Number of participants with adverse events (AEs)

Serious Adverse Events

Time Frame	From informed consent until 30 days after last dose + subsequent treatment-related events reported (maximum up to 4 years).
Additional Description	No text entered.

Reporting Groups

	Description
Olaparib 300 mg twice daily (bd)	Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
Placebo	Randomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Serious Adverse Events

Olaparib 300 mg twice daily (bd)

Placebo

Total, serious adverse events

# participants affected / at risk

22/91 (24.18%)

9/60 (15.00%)

Infections and infestations

Abdominal infection¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Infections and infestations

Bartholinitis¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Infections and infestations

Pneumonia¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Infections and infestations

Urinary tract infection¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Blood and lymphatic system disorders

Anaemia¹

# participants affected / at risk

6/91 (6.59%)

0/60 (0.00%)

Blood and lymphatic system disorders

Febrile Neutropenia¹

# participants affected / at risk

0/91 (0.00%)

1/60 (1.67%)

Endocrine disorders

Hypothyroidism¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Metabolism and nutrition disorders

Decreased appetite¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Metabolism and nutrition disorders

Hyperglycaemia¹

# participants affected / at risk

0/91 (0.00%)

1/60 (1.67%)

Nervous system disorders

Cerebrovascular accident¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Nervous system disorders

Embolic stroke¹

# participants affected / at risk

0/91 (0.00%)

1/60 (1.67%)

Nervous system disorders

Transient ischaemic attack¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Cardiac disorders

Cardiac failure¹

# participants affected / at risk

1/91 (1.10%)

1/60 (1.67%)

Vascular disorders

Vascular stenosis¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Respiratory, thoracic and mediastinal disorders

Pleural effusion¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Respiratory, thoracic and mediastinal disorders

Pneumothorax¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Gastrointestinal disorders

Abdominal pain¹

# participants affected / at risk

3/91 (3.30%)

1/60 (1.67%)

Gastrointestinal disorders

Constipation¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Gastrointestinal disorders

Duodenal perforation¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Gastrointestinal disorders

Gastric varices haemorrhage¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Gastrointestinal disorders

Incarcerated inguinal hernia¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Gastrointestinal disorders

Large intestinal obstruction¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Gastrointestinal disorders

Melaena¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Gastrointestinal disorders

Obstruction gastric¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Gastrointestinal disorders

Pancreatitis¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Gastrointestinal disorders

Vomiting¹

# participants affected / at risk

1/91 (1.10%)

3/60 (5.00%)

Hepatobiliary disorders

Bile duct obstruction¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Hepatobiliary disorders

Cholangitis¹

# participants affected / at risk

2/91 (2.20%)

1/60 (1.67%)

Hepatobiliary disorders

Cholecystitis¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

General disorders

General physical health deterioration¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Investigations

Platelet count decreased¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Injury, poisoning and procedural complications

Anastomotic haemorrhage¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Product Issues

Device occlusion¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

Product Issues

Stent malfunction¹

# participants affected / at risk

1/91 (1.10%)

0/60 (0.00%)

General disorders

Pyrexia¹

# participants affected / at risk

0/91 (0.00%)

2/60 (3.33%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA version 21.1

Other Adverse Events

Time Frame	From informed consent until 30 days after last dose + subsequent treatment-related events reported (maximum up to 4 years).
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Olaparib 300 mg twice daily (bd)	Randomised participants received orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.
Placebo	Randomised participants received placebo tablets orally 300 mg bd which were made up of 2 x 150 mg tablets bd with 100 mg tablets used to manage dose reductions.

Other Adverse Events

Olaparib 300 mg twice daily (bd)

Placebo

Total, other (not including serious) adverse events

# participants affected / at risk

87/91 (95.60%)

56/60 (93.33%)

Gastrointestinal disorders

Nausea¹

# participants affected / at risk

41/91 (45.05%)

14/60 (23.33%)

Gastrointestinal disorders

Diarrhoea¹

# participants affected / at risk

26/91 (28.57%)

9/60 (15.00%)

Gastrointestinal disorders

Abdominal pain¹

# participants affected / at risk

23/91 (25.27%)

14/60 (23.33%)

Gastrointestinal disorders

Constipation¹

# participants affected / at risk

20/91 (21.98%)

6/60 (10.00%)

Gastrointestinal disorders

Vomiting¹

# participants affected / at risk

18/91 (19.78%)

8/60 (13.33%)

Gastrointestinal disorders

Stomatitis¹

# participants affected / at risk

7/91 (7.69%)

3/60 (5.00%)

Gastrointestinal disorders

Abdominal pain upper¹

# participants affected / at risk

6/91 (6.59%)

8/60 (13.33%)

Gastrointestinal disorders

Dry mouth¹

# participants affected / at risk

6/91 (6.59%)

1/60 (1.67%)

Gastrointestinal disorders

Dyspepsia¹

# participants affected / at risk

5/91 (5.49%)

5/60 (8.33%)

Gastrointestinal disorders

Abdominal distension¹

# participants affected / at risk

4/91 (4.40%)

6/60 (10.00%)

Gastrointestinal disorders

Flatulence¹

# participants affected / at risk

2/91 (2.20%)

4/60 (6.67%)

General disorders

Fatigue¹

# participants affected / at risk

41/91 (45.05%)

16/60 (26.67%)

General disorders

Asthenia¹

# participants affected / at risk

15/91 (16.48%)

5/60 (8.33%)

General disorders

Pyrexia¹

# participants affected / at risk

12/91 (13.19%)

3/60 (5.00%)

General disorders

Oedema peripheral¹

# participants affected / at risk

8/91 (8.79%)

5/60 (8.33%)

Musculoskeletal and connective tissue disorders

Back pain¹

# participants affected / at risk

17/91 (18.68%)

10/60 (16.67%)

Musculoskeletal and connective tissue disorders

Arthralgia¹

# participants affected / at risk

14/91 (15.38%)

6/60 (10.00%)

Musculoskeletal and connective tissue disorders

Muscle spasms¹

# participants affected / at risk

6/91 (6.59%)

2/60 (3.33%)

Musculoskeletal and connective tissue disorders

Pain in extremity¹

# participants affected / at risk

6/91 (6.59%)

4/60 (6.67%)

Musculoskeletal and connective tissue disorders

Musculoskeletal pain¹

# participants affected / at risk

5/91 (5.49%)

3/60 (5.00%)

Musculoskeletal and connective tissue disorders

Myalgia¹

# participants affected / at risk

5/91 (5.49%)

3/60 (5.00%)

Musculoskeletal and connective tissue disorders

Flank pain¹

# participants affected / at risk

1/91 (1.10%)

4/60 (6.67%)

Nervous system disorders

Dysgeusia¹

# participants affected / at risk

10/91 (10.99%)

3/60 (5.00%)

Nervous system disorders

Neuropathy peripheral¹

# participants affected / at risk

7/91 (7.69%)

7/60 (11.67%)

Nervous system disorders

Dizziness¹

# participants affected / at risk

6/91 (6.59%)

3/60 (5.00%)

Nervous system disorders

Headache¹

# participants affected / at risk

6/91 (6.59%)

8/60 (13.33%)

Nervous system disorders

Peripheral sensory neuropathy¹

# participants affected / at risk

6/91 (6.59%)

2/60 (3.33%)

Blood and lymphatic system disorders

Anaemia¹

# participants affected / at risk

23/91 (25.27%)

10/60 (16.67%)

Blood and lymphatic system disorders

Neutropenia¹

# participants affected / at risk

7/91 (7.69%)

4/60 (6.67%)

Blood and lymphatic system disorders

Thrombocytopenia¹

# participants affected / at risk

7/91 (7.69%)

4/60 (6.67%)

Metabolism and nutrition disorders

Decreased appetite¹

# participants affected / at risk

22/91 (24.18%)

4/60 (6.67%)

Metabolism and nutrition disorders

Hyperglycaemia¹

# participants affected / at risk

8/91 (8.79%)

1/60 (1.67%)

Skin and subcutaneous tissue disorders

Rash¹

# participants affected / at risk

11/91 (12.09%)

2/60 (3.33%)

Skin and subcutaneous tissue disorders

Pruritus¹

# participants affected / at risk

9/91 (9.89%)

4/60 (6.67%)

Investigations

Alanine aminotransferase increased¹

# participants affected / at risk

8/91 (8.79%)

1/60 (1.67%)

Investigations

Aspartate aminotransferase increased¹

# participants affected / at risk

6/91 (6.59%)

1/60 (1.67%)

Investigations

Blood creatinine increased¹

# participants affected / at risk

6/91 (6.59%)

1/60 (1.67%)

Investigations

Blood alkaline phosphatase increased¹

# participants affected / at risk

5/91 (5.49%)

3/60 (5.00%)

Investigations

Platelet count decreased¹

# participants affected / at risk

5/91 (5.49%)

0/60 (0.00%)

Psychiatric disorders

Insomnia¹

# participants affected / at risk

7/91 (7.69%)

1/60 (1.67%)

Psychiatric disorders

Anxiety¹

# participants affected / at risk

5/91 (5.49%)

2/60 (3.33%)

Psychiatric disorders

Depression¹

# participants affected / at risk

5/91 (5.49%)

0/60 (0.00%)

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹

# participants affected / at risk

10/91 (10.99%)

3/60 (5.00%)

Respiratory, thoracic and mediastinal disorders

Cough¹

# participants affected / at risk

8/91 (8.79%)

2/60 (3.33%)

Infections and infestations

Nasopharyngitis¹

# participants affected / at risk

11/91 (12.09%)

2/60 (3.33%)

Infections and infestations

Influenza¹

# participants affected / at risk

5/91 (5.49%)

0/60 (0.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA version 21.1

Primary Outcome Measures:

Progression free survival (PFS) by central review of modified RECIST 1.1 [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
Efficacy by assessment of PFS (time from randomisation to objective disease progression according to modified Response Evaluation Criteria in Solid Tumours (RECIST 1.1) or death) of olaparib maintenance monotherapy compared to placebo, using blinded independent central review (BICR) of radiological scans.

Secondary Outcome Measures:

Overall survival (OS) [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
Efficacy by assessment of OS (time from randomisation to death by any cause) of olaparib maintenance monotherapy compared to placebo
Time from randomisation to second progression or death (PFS2) [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
Efficacy by assessment of PFS2 (time from randomisation to second progression, defined as objective radiological or symptomatic progression, or death) of olaparib maintenance monotherapy compared to placebo.
Time from randomisation to first subsequent therapy or death (TFST) [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
Efficacy by assessment of TFST (time from randomisation to the earlier of first subsequent therapy following study treatment discontinuation, or death) of olaparib maintenance monotherapy compared to placebo.
Time from randomisation to second subsequent therapy or death (TSST) [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
Efficacy by assessment of TSST (time from randomisation to the earlier of second subsequent therapy following study treatment discontinuation, or death) of olaparib maintenance monotherapy compared to placebo.
Time from randomisation to study treatment discontinuation or death (TDT) [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
Efficacy by assessment of TDT (time from randomisation to the earlier of study treatment discontinuation or death) of olaparib maintenance monotherapy compared to placebo. compared to placebo.
Objective response rate by BICR using modified RECIST 1.1 [ Time Frame: Up to 4 years. ] [ Designated as safety issue: No ]
Efficacy by assessment of objective response rate according to modified RECIST 1.1 of olaparib maintenance monotherapy compared to placebo
Disease control rate by BICR using modified RECIST 1.1 [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
Efficacy by assessment of disease control rate according to modified RECIST 1.1 of olaparib maintenance monotherapy compared to placebo.
Adjusted mean change from baseline in global quality of life (QoL) score from the EORTC-QLQ-C30 questionnaire [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
Assessment of the effect of olaparib on health-related quality of life (QoL) as measured by the EORTC-QLQ-C30 global QoL scale
Safety and tolerability of olaparib [ Time Frame: Up to 4 years ] [ Designated as safety issue: Yes ]
Assessment of adverse events (AEs), physical examination, vital signs including blood pressure (BP), pulse, electrocardiogram (ECG) and laboratory findings including clinical chemistry and haematology.
Improvement rate of global quality of life (QoL) [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
Assessment of the effect of olaparib on improvement rate of global health status/QoL and pancreatic pain as measured by the EORTC-QLQ-C30 global QoL scale and the PAN-26 pancreatic pain scale.

Other Pre-specified Outcome Measures:

[ Time Frame: ] [ Designated as safety issue: ]

Arms	Assigned Interventions
Experimental: Olaparib Olaparib tablets po. 300 mg twice daily	Drug: Olaparib Tablet –100mg Drug: Olaparib Tablet-150mg
Placebo Comparator: Placebo Placebo tablets twice daily	Drug: Placebo Match Olaparib 100mg placebo Drug: Placebo Match Olaparib 150mg placebo

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: This submission /document contains trade secrets and confidential commercial information, disclosure of which is prohibited without providing advance notice to AstraZeneca and opportunity to object.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Global Clinical Leader
Organization:	AstraZeneca AB
Phone	1-877-240-9479
E-mail:	information.center@astrazeneca.com