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: 1. Overall Survival (OS) and 2. 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1.1 as assessed by blinded independent central review (BICR) As of Amendment 06, the Data Monitoring Committee (DMC) is no longer applicable.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 criteria for discontinuation are met. Participants who are still on study treatment and deriving clinical benefit will no longer have tumor response assessments by BICR. However, local tumor imaging assessments should continue per standard of care (SOC) schedule. In addition, electronic patient-reported outcome (ePRO) assessments will no longer be performed and biomarker samples will no longer be collected.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
793
IV infusion
Oral tablets
Oral tablets
Oral tablets
Oral tablets or oral capsules
Oral tablets
St. Joseph Heritage Healthcare ( Site 0069)
Fullerton, California, United States
UCLA Hematology/Oncology - Santa Monica ( Site 0081)
Los Angeles, California, United States
Sibley Memorial Hospital ( Site 0096)
Washington D.C., District of Columbia, United States
Georgia Cancer Center at Augusta University ( Site 0026)
Augusta, Georgia, United States
Quincy Medical Group ( Site 0021)
Quincy, Illinois, United States
Overall Survival (OS)
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.
Time frame: Up to ~31 months
Radiographic Progression-Free Survival (rPFS)
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.
Time frame: Up to ~26 months
Time to Initiation of the First Subsequent Anticancer Therapy (TFST)
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.
Time frame: Up to ~26 months
Objective Response Rate (ORR)
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 percentage of participants who experienced CR or PR as assessed by BICR is presented.
Time frame: Up to ~31 months
Duration of Response (DOR)
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. DOR as assessed by BICR is presented.
Time frame: Up to ~26 months
Time to Prostate-Specific Antigen (PSA) Progression
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.
Time frame: Up to ~31 months
Time to First Symptomatic Skeletal-Related Event (SSRE)
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
Time frame: Up to ~31 months
Time to Radiographic Soft Tissue Progression
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.
Time frame: Up to ~31 months
Time to Pain Progression (TTPP)
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. Participants who had more than 2 consecutive visits that were not evaluable for pain progression were censored at the last evaluable assessment.
Time frame: Up to ~31 months
Number of Participants Who Experience an Adverse Event (AE)
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 number of participants who experienced an adverse event are presented.
Time frame: Up to ~55 months
Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)
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 number of participants who discontinue study treatment due to an AE are presented.
Time frame: Up to ~1461 Days
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Tulane Cancer Center ( Site 0066)
New Orleans, Louisiana, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 0005)
Baltimore, Maryland, United States
Chesapeake Urology Research Associates ( Site 0076)
Towson, Maryland, United States
Beth Israel Deaconess Medical Ctr. ( Site 0093)
Boston, Massachusetts, United States
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