7339-010

Merck Sharp & Dohme LLC

126 East Lincoln Avenue, P.O. Box 2000, Rahway, NJ, United States, 07065

Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@msd.com

Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@msd.com

No

No

No

Final

27 Jan 2024

Yes

14 Mar 2022

Yes

27 Jan 2024

No

The purpose of this study is to assess the efficacy and safety of the combination of the polyadenosine 5'-diphosphoribose poly (ADP-ribose) polymerase (PARP) inhibitor olaparib and pembrolizumab in the treatment of participants with mCRPC who have failed to respond to either abiraterone acetate or enzalutamide (but not both) and to chemotherapy. The primary study hypotheses are that the combination of pembrolizumab plus olaparib is superior to abiraterone acetate or enzalutamide with respect to: Overall Survival (OS) and Radiographic progression-free survival (rPFS) per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 as assessed by blinded independent central review (BICR) As of Amendment 06, the Data Monitoring Committee (DMC) is no longer applicable. Participants still on treatment may have the option to continue receiving study intervention or SOC if they are deriving clinical benefit, until discontinuation criteria are met.

This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.

02 May 2019

No

Yes

Australia: 65

Austria: 24

Brazil: 26

Canada: 42

Argentina: 38

Chile: 32

France: 89

Germany: 38

Ireland: 14

Israel: 30

Italy: 53

Japan: 50

Korea, Democratic People's Republic of: 71

Netherlands: 61

New Zealand: 11

Russian Federation: 35

Spain: 37

Taiwan: 31

United Kingdom: 18

United States: 28

793

316

0

0

0

0

0

0

188

600

5

Overall Study (overall period)

Randomised - controlled

Yes

Olaparib

MK-7339

MK-7339 AZD-2281 LYNPARZA®

Tablet

Oral use

600 mg

Pembrolizumab

MK-3475

MK-3475 KEYTRUDA®

Solution for infusion

Intravenous use

200 mg

Abiraterone acetate

ZYTIGA® CB-7630 JNJ-212082

Tablet

Oral use

1000 mg

Prednisone

Tablet

Oral use

10 mg

Enzalutamide

XTANDI® MDV-3100 ASP-9785

Tablet

Oral use

160 mg

Prednisolone

Tablet

Oral use

10 mg

Pembrolizumab + Olaparib

Next-generation hormonal agent monotherapy (NHA)

Pembrolizumab + Olaparib

Next-generation hormonal agent monotherapy (NHA)

Overall survival (OS) is defined as the time from randomization to death due to any cause. The nonparametric Kaplan-Meier method was used to estimate the survival curves. The analysis population included all randomized participants.

Primary

Up to ~31 months

Treatment difference in OS assessed by the stratified log-rank test stratified by measurable disease status and prior NHA treatment.

Pembrolizumab + Olaparib v Next-generation hormonal agent monotherapy (NHA)

793

Pre-specified

0.94

2-sided

rPFS is defined as the time from randomization to the first documented progressive disease (PD) per PCWG-modified RECIST 1.1 based on BICR or death due to any cause, whichever occurred first. Per PCWG-modified RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions or ≥2 new bone lesions was also considered PD. PCWG-modified RECIST is similar to RECIST 1.1 with the exception that a confirmation assessment of PD (>4 weeks after the initial PD) is required for participants who remain on treatment following a documented PD per RECIST 1.1 and PCWG rules include new bone lesions. The rPFS per PCWG-modified RECIST as assessed by BICR for all participants is presented. The nonparametric Kaplan-Meier method was used to estimate the survival curves. The analysis population included all randomized participants.

Primary

Up to ~26 months

Treatment difference in rPFS aassessed by the stratified log-rank test stratified by measurable disease status and prior NHA treatment.

Pembrolizumab + Olaparib v Next-generation hormonal agent monotherapy (NHA)

793

Pre-specified

1.02

2-sided

ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions per RECIST 1.1 and no evidence of disease (NED) bone scan) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions per RECIST 1.1 and Non-PD, non-evaluable (NE), or NED bone scan or CR with non-PD or NE bone scan.) The analysis population included all randomized participants who had measurable disease at baseline. The percentage of participants who experienced CR or PR as assessed by BICR is presented.

Secondary

Up to ~31 months

Treatment difference in ORR assessed by the stratified log-rank test stratified by measurable disease status and prior NHA treatment.

Pembrolizumab + Olaparib v Next-generation hormonal agent monotherapy (NHA)

363

Pre-specified

10.9

2-sided

TFST is the time from randomization to initiation of the first subsequent anticancer therapy defined as the first anti-cancer treatment not part of the study arm for a given participant, or death, whichever occurs first. The nonparametric Kaplan-Meier method was used to estimate the survival curves. The analysis population included all randomized participants.

Secondary

Up to ~26 months

Treatment difference in TFTS assessed by the stratified log-rank test stratified by measurable disease status and prior NHA treatment.

Pembrolizumab + Olaparib v Next-generation hormonal agent monotherapy (NHA)

793

Pre-specified

0.86

2-sided

DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per PCWG-modified RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of ≥ 2 new bone lesions is also considered PD. The analysis population included all randomized participants who experience a confirmed CR or PR and had measurable disease at baseline. DOR as assessed by BICR is presented. 9999 = upper limit not reached at the time of data cut-off due to insufficient number of responding participants with relapse.

Secondary

Up to ~26 months

Time to PSA progression is defined as the time from randomization to PSA progression. PSA progression date is defined as the date of: 1) ≥25% increase and ≥2 ng/mL above the nadir, confirmed by a second value ≥3 weeks later if there is PSA decline from baseline, OR 2) ≥25% increase and ≥2 ng/mL increase from baseline beyond 12 weeks if there is no PSA decline from baseline. The nonparametric Kaplan-Meier method was used to estimate the survival curves. The analysis population included all randomized participants.

Secondary

Up to ~31 months

Treatment difference in Time to PSA progression assessed by the stratified log-rank test stratified by measurable disease status and prior NHA treatment.

Pembrolizumab + Olaparib v Next-generation hormonal agent monotherapy (NHA)

793

Pre-specified

1.11

2-sided

SSRE is defined as the time from randomization to the first symptomatic skeletal-related event, defined as whichever occurs first: - First use of external-beam radiation therapy (EBRT) to prevent or relieve skeletal symptoms; - Occurrence of new symptomatic pathologic bone fracture (vertebral or nonvertebral); - Occurrence of spinal cord compression; or - Tumor-related orthopedic surgical intervention The analysis population included all randomized participants. 9999 = lower limit, median and upper limit not reached at the time of data cut-off due to insufficient number of responding participants with relapse.

Secondary

Up to ~31 months

Treatment difference in Time to first SSRE assessed by the stratified log-rank test stratified by measurable disease status and prior NHA treatment.

Pembrolizumab + Olaparib v Next-generation hormonal agent monotherapy (NHA)

793

Pre-specified

0.54

2-sided

Time to radiographic soft tissue progression is defined as the time from randomization to radiographic soft tissue progression per soft tissue rule of PCWG-modified RECIST 1.1. Progression is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. Time to radiographic soft tissue progression as assessed by BICR is presented. The analysis population included all randomized participants.

Secondary

Up to ~31 months

Treatment difference in Time to radiographic soft tissue progression assessed by the stratified log-rank test stratified by measurable disease status and prior NHA treatment.

Pembrolizumab + Olaparib v Next-generation hormonal agent monotherapy (NHA)

793

Pre-specified

0.79

2-sided

TTPP is defined as the time from randomization to pain progression as determined by Item 3 of the Brief Pain Inventory Short Form (BPI-SF) and by the Analgesic Quantification Algorithm (AQA) score. Pain progression is defined as: 1) For participants who are asymptomatic at baseline, a ≥2-point change from baseline in the average (4-7 days) BPI-SF item 3 score at 2 consecutive visits OR initiation of opioid use for pain 2) For participants who are symptomatic at baseline (average BPI-SF Item 3 score >0 and/or currently taking opioids), a ≥2-point change from baseline in the average BPI-SF Item 3 score and an average worst pain score ≥4 and no decrease in average opioid use (≥1-point decrease in AQA score from a starting value of 2 or higher) OR any increase in opioid use at 2 consecutive follow-up visits. The analysis population included all participants who have at least 1 assessment available and have received at least 1 dose of study intervention. 9999 = upper limit not reached.

Secondary

Up to ~31 months

Treatment difference in TTPP assessed by the stratified log-rank test stratified by measurable disease status and prior NHA treatment.

Pembrolizumab + Olaparib v Next-generation hormonal agent monotherapy (NHA)

750

Pre-specified

0.95

2-sided

An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The analysis population included all randomized participants who received at least 1 dose of study intervention. The number of participants who experienced an adverse event are presented.

Secondary

Up to ~55 months

An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The analysis population included all randomized participants who received at least 1 dose of study intervention. The number of participants who discontinue study treatment due to an AE are presented.

Secondary

Up to ~1461 Days

Up to ~55 months

All-cause mortality: All allocated participants. AEs: All allocated participants who received =1 dose of study intervention. MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs.

26.1

Next-generation hormonal agent monotherapy (NHA)

Pembrolizumab + Olaparib