An Investigational Immunotherapy Study of Nivolumab in Combination With Rucaparib, Docetaxel, or Enzalutamide in Metastatic Castration-resistant Prostate Cancer

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and efficacy of nivolumab in combination with rucaparib, docetaxel, or enzalutamide in participants with castration-resistant prostate cancer that has spread.

Official Title
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A Phase 2 Study of Nivolumab in Combination With Either Rucaparib, Docetaxel, or Enzalutamide in Men With Castration-resistant Metastatic Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Biological: nivolumab
* Drug: docetaxel
* Drug: enzalutamide
* Drug: rucaparib
* Drug: prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic confirmation of adenocarcinoma of the prostate Evidence of stage IV disease on previous bone, CT, and/or MRI scan Ongoing androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone (GnRH) analogue or bilateral orchiectomy Mandatory plasma and fresh or archival tumor tissue must be submitted Exclusion Criteria: Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the breast Participants with active brain metastases Participants must have recovered from the effects of major surgery requiring general anesthesia or significant traumatic injury at least 14 days before treatment arm assignment Other protocol defined inclusion/exclusion criteria could apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: nivolumab + rucaparib<br>Specified dose on specified days | Biological: nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558, Opdivo;Drug: rucaparib<br>* Specified dose on specified days<br>|
| Experimental: nivolumab + docetaxel + prednisone<br>Specified dose on specified days | Biological: nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558, Opdivo;Drug: docetaxel<br>* Specified dose on specified days<br>Drug: prednisone<br>* Specified dose on specified days<br>|
| Experimental: nivolumab + enzalutamide<br>Specified dose on specified days | Biological: nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558, Opdivo;Drug: enzalutamide<br>* Specified dose on specified days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate Per Prostate Cancer Clinical Trials Working Group 3 (ORR-PCWG3) | Objective response rate per prostate cancer clinical trials working group 3 (ORR-PCWG3) for target lesions and assessed by MRI is the percentage of participants who have a confirmed complete or partial best overall response (BOR) per PCWG3 among treated participants who have measurable disease | Up to approximately 36 months | 
| Prostate-Specific Antigen Response Rate (RR-PSA) | Prostate-specific antigen response rate (RR-PSA) is the percentage of treated participants with a 50% or greater decrease in PSA from baseline to the lowest post-baseline PSA result | Up to approximately 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiographic Progression-Free Survival (rPFS) | Radiographic progress-free survival (rPFS) is the time between treatment initiation and the first date of documented progression or death due to any cause, whichever occurs first assessed by the investigator per PCWG3 | Up to approximately 36 months | 
| Time to Response Per Prostate Cancer Clinical Trials Working Group 3 (TTR-PCWG3) | Time to response per prostate cancer clinical trials working group 3 (TTR-PCWG3) is the time from treatment initiation to the date of the first documented complete response (CR) or partial response (PR) per PCWG3 | Up to approximately 36 months | 
| Duration of Response Per Prostate Cancer Clinical Trials Working Group 3 (DOR-PCWG3) | Duration of response per prostate cancer clinical trials working group 3 (DOR-PCWG3) is the time between the date of first response (complete response/partial response per PCWG3) to the date of first documented radiographic progression per PCWG3 or death due to any cause | Up to approximately 36 months | 
| Prostate-Specific Antigen Time to Progression (TTP-PSA) | Prostate-specific antigen time to progression (TTP-PSA) is the time between treatment initiation to the date of PSA progression per prostate cancer clinical trails working group 3 | Up to approximately 36 months | 
| Overall Survival (OS) | Overall Survival (OS) is the time between treatment initiation and the date of death from any cause. For participants who are alive, their survival time will be censored at the last date that they were known to be alive. OS will be censored for participants at the date of treatment initiation if they had no follow-up | Up to approximately 36 months | 
| Number of Participants With Adverse Events (AEs) | Number of Participants with any grade adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation, and immune-mediated AEs using the Common Toxicity Criteria Grade for Adverse Events (CTCAE V4) | From first dose to up to 30 days post last dose (Up to 34 months) | 
| Number of Deaths | Number of deaths in all treated participants | Up to 36 months | 
| Number of Participants With Laboratory Abnormalities in Specific Liver Tests | Number of participants with laboratory abnormalities in specific liver tests based on SI conventional units to assess the overall safety and tolerability of BMS-986213 in combination with chemotherapy vs. Nivolumab in combination with chemotherapy. The number of participants with the following laboratory abnormalities from on-treatment evaluations will be summarized: ALT or AST > 3 x ULN, > 5 x ULN, > 10 x ULN and > 20 x ULN Total bilirubin > 2 x ULN ALP > 1.5 x ULN Concurrent (within 1 day) ALT or AST > 3 x ULN and total bilirubin > 1.5 x ULN Concurrent (within 30 days) ALT or AST > 3 x ULN and total bilirubin > 1.5 x ULN Concurrent (within 1 day) ALT or AST > 3 x ULN and total bilirubin > 2 x ULN Concurrent (within 30 days) ALT or AST > 3 x ULN and total bilirubin > 2 x ULN | From first dose to up to 30 days post last dose (up to 34 months) | 
| Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | Number of participants with laboratory abnormalities in specific thyroid tests based on US conventional units. The number of participants with the following laboratory abnormalities from on-treatment evaluations will be summarized: TSH value > ULN and with baseline TSH value <= ULN with at least one FT3/FT4 test value < LLN within 2-week window after the abnormal TSH test with all FT3/FT4 test values >= LLN within 2-week window after the abnormal TSH test with FT3/FT4 missing within 2-week window after the abnormal TSH test. TSH < LLN and with baseline TSH value >= LLN with at least one FT3/FT4 test value > ULN within 2-week window after the abnormal TSH test with all FT3/FT4 test values <= ULN within 2-week window after the abnormal TSH test with FT3/FT4 missing within 2-week window after the abnormal TSH test | From first dose to up to 30 days post last dose (Up to 34 months) | 
| Number of Participants With Laboratory Values Change From Baseline | Number of participants changed from baseline in laboratory values of worst toxicity grade (grade 0= wnl, grade 1= mild, grade 2= moderate, grade 3= severe) based on US conventional units by cohort | From first dose to up to 30 days post last dose (Up to 34 months) |