Prostate Cancer
Conditions
Brief summary
The purpose of this study is to assess safety and efficacy of nivolumab in combination with rucaparib, docetaxel, or enzalutamide in participants with castration-resistant prostate cancer that has spread.
Interventions
BIOLOGICALnivolumab
Specified dose on specified days
DRUGdocetaxel
Specified dose on specified days
DRUGenzalutamide
Specified dose on specified days
DRUGrucaparib
Specified dose on specified days
DRUGprednisone
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Clovis Oncology, Inc.
Astellas Pharma Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate Per Prostate Cancer Clinical Trials Working Group 3 (ORR-PCWG3) | Up to approximately 36 months | 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 |
| Prostate-Specific Antigen Response Rate (RR-PSA) | Up to approximately 36 months | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Radiographic Progression-Free Survival (rPFS) | Up to approximately 84 months | 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 Prostate Cancer Clinical Trials Working Group 3 (PCWG3) |
| Time to Response Per Prostate Cancer Clinical Trials Working Group 3 (TTR-PCWG3) | Up to approximately 84 months | 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 Prostate Cancer Clinical Trials Working Group 3 (PCWG3) |
| Duration of Response Per Prostate Cancer Clinical Trials Working Group 3 (DOR-PCWG3) | Up to approximately 84 months | 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 Prostate Cancer Clinical Trials Working Group 3 (PCWG3) or death due to any cause |
| Prostate-Specific Antigen Time to Progression (TTP-PSA) | Up to approximately 84 months | Prostate-specific antigen time to progression (TTP-PSA) is the time between treatment initiation to the date of PSA progression per prostate cancer clinical trials working group 3 (PCWG3) |
| Overall Survival (OS) | Up to approximately 84 months | 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 |
| Number of Participants With Adverse Events (AEs) | From first dose to up to 30 days post last dose (Up to 82 months) | 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) |
| Number of Participants Who Died | Up to 84 months | Number of participants who died due to any cause. |
| Number of Participants With Laboratory Abnormalities in Specific Liver Tests | From first dose to up to 30 days post last dose (up to 82 months) | 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 |
| Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | From first dose to up to 30 days post last dose (Up to 82 months) | 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 |
| Number of Participants With Laboratory Values Change From Baseline | From first dose to up to 30 days post last dose (Up to 82 months) | 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 |
Countries
Argentina, Australia, Brazil, Canada, Chile, Colombia, France, Germany, Mexico, Spain, United States
Contacts
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Participant flow
Pre-assignment details
292 participants treated
Participants by arm
| Arm | Count |
|---|---|
| Arm A1 Nivolumab 480 mg IV Q4W + Rucaparib 600 mg PO BID for participants who have at lease 1 but no more than 2 prior chemotherapy regimens | 88 |
| Arm A2 Nivolumab 480 mg IV Q4W + Rucaparib 600 mg PO BID for participants who have not received prior chemotherapy regimen | 71 |
| Arm B Nivolumab 360 mg IV Q3W + Docetaxel 75 mg/m2 IV Q3W + Prednisone 5 mg PO BID | 84 |
| Arm C Nivolumab 480 mg IV Q4W + Enzalutamide 160 mg PO QD | 49 |
| Total | 292 |
Baseline characteristics
| Characteristic | Arm A1 | Total | Arm C | Arm B | Arm A2 |
|---|---|---|---|---|---|
| Age, Continuous | 66.6 Years STANDARD_DEVIATION 8.3 | 69.4 Years STANDARD_DEVIATION 8.4 | 69.8 Years STANDARD_DEVIATION 8 | 70.3 Years STANDARD_DEVIATION 7.6 | 70.7 Years STANDARD_DEVIATION 9.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 4 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 15 Participants | 2 Participants | 8 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 10 Participants | 25 Participants | 5 Participants | 5 Participants | 5 Participants |
| Race (NIH/OMB) White | 72 Participants | 248 Participants | 42 Participants | 70 Participants | 64 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 88 Participants | 292 Participants | 49 Participants | 84 Participants | 71 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 79 / 88 | 66 / 71 | 76 / 84 | 47 / 49 |
| other Total, other adverse events | 87 / 88 | 70 / 71 | 83 / 84 | 48 / 49 |
| serious Total, serious adverse events | 53 / 88 | 45 / 71 | 50 / 84 | 25 / 49 |
Outcome results
Primary
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
Time frame: Up to approximately 36 months
Population: All response evaluable participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A1 | Objective Response Rate Per Prostate Cancer Clinical Trials Working Group 3 (ORR-PCWG3) | Overall | 10.3 Percentage of participants |
| Arm A1 | Objective Response Rate Per Prostate Cancer Clinical Trials Working Group 3 (ORR-PCWG3) | Homologous Recombination Deficiency (HRD+) | 17.2 Percentage of participants |
| Arm A2 | Objective Response Rate Per Prostate Cancer Clinical Trials Working Group 3 (ORR-PCWG3) | Homologous Recombination Deficiency (HRD+) | 25.0 Percentage of participants |
| Arm A2 | Objective Response Rate Per Prostate Cancer Clinical Trials Working Group 3 (ORR-PCWG3) | Overall | 15.4 Percentage of participants |
| Arm B | Objective Response Rate Per Prostate Cancer Clinical Trials Working Group 3 (ORR-PCWG3) | Overall | 40.0 Percentage of participants |
| Arm B | Objective Response Rate Per Prostate Cancer Clinical Trials Working Group 3 (ORR-PCWG3) | Homologous Recombination Deficiency (HRD+) | 36.8 Percentage of participants |
| Arm C | Objective Response Rate Per Prostate Cancer Clinical Trials Working Group 3 (ORR-PCWG3) | Overall | 11.1 Percentage of participants |
| Arm C | Objective Response Rate Per Prostate Cancer Clinical Trials Working Group 3 (ORR-PCWG3) | Homologous Recombination Deficiency (HRD+) | 20.0 Percentage of participants |
Primary
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
Time frame: Up to approximately 36 months
Population: All response evaluable participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A1 | Prostate-Specific Antigen Response Rate (RR-PSA) | Overall | 11.9 Percentage of participants |
| Arm A1 | Prostate-Specific Antigen Response Rate (RR-PSA) | Homologous Recombination Deficiency (HRD+) | 18.2 Percentage of participants |
| Arm A2 | Prostate-Specific Antigen Response Rate (RR-PSA) | Homologous Recombination Deficiency (HRD+) | 41.9 Percentage of participants |
| Arm A2 | Prostate-Specific Antigen Response Rate (RR-PSA) | Overall | 27.3 Percentage of participants |
| Arm B | Prostate-Specific Antigen Response Rate (RR-PSA) | Overall | 46.9 Percentage of participants |
| Arm B | Prostate-Specific Antigen Response Rate (RR-PSA) | Homologous Recombination Deficiency (HRD+) | 50.0 Percentage of participants |
| Arm C | Prostate-Specific Antigen Response Rate (RR-PSA) | Overall | 34.1 Percentage of participants |
| Arm C | Prostate-Specific Antigen Response Rate (RR-PSA) | Homologous Recombination Deficiency (HRD+) | 50.0 Percentage of participants |
Secondary
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
Time frame: Up to approximately 36 months
Secondary
Number of Deaths
Number of deaths in all treated participants
Time frame: Up to 36 months
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A1 | Number of Deaths | 59 Deaths |
| Arm A2 | Number of Deaths | 42 Deaths |
| Arm B | Number of Deaths | 44 Deaths |
| Arm C | Number of Deaths | 28 Deaths |
Secondary
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)
Time frame: From first dose to up to 30 days post last dose (Up to 34 months)
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A1 | Number of Participants With Adverse Events (AEs) | Immune-mediated AEs (Rash) | 5 Participants |
| Arm A1 | Number of Participants With Adverse Events (AEs) | Adverse Events (AEs) | 88 Participants |
| Arm A1 | Number of Participants With Adverse Events (AEs) | Immune-mediated AEs (Hypersensitivity/Infusion Reactions) | 0 Participants |
| Arm A1 | Number of Participants With Adverse Events (AEs) | Immune-mediated AEs (Pneumonitis) | 1 Participants |
| Arm A1 | Number of Participants With Adverse Events (AEs) | Immune-mediated AEs (Nephritis/Renal Dysfunction) | 2 Participants |
| Arm A1 | Number of Participants With Adverse Events (AEs) | Serious Adverse Events (SAEs) | 47 Participants |
| Arm A1 | Number of Participants With Adverse Events (AEs) | Immune-mediated AEs (Hepatitis) | 8 Participants |
| Arm A1 | Number of Participants With Adverse Events (AEs) | Immune-mediated AEs (Diarrhea/Colitis) | 4 Participants |
| Arm A1 | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation | 39 Participants |
| Arm A2 | Number of Participants With Adverse Events (AEs) | Immune-mediated AEs (Diarrhea/Colitis) | 4 Participants |
| Arm A2 | Number of Participants With Adverse Events (AEs) | Immune-mediated AEs (Hepatitis) | 7 Participants |
| Arm A2 | Number of Participants With Adverse Events (AEs) | Adverse Events (AEs) | 71 Participants |
| Arm A2 | Number of Participants With Adverse Events (AEs) | Immune-mediated AEs (Nephritis/Renal Dysfunction) | 3 Participants |
| Arm A2 | Number of Participants With Adverse Events (AEs) | Immune-mediated AEs (Hypersensitivity/Infusion Reactions) | 1 Participants |
| Arm A2 | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation | 26 Participants |
| Arm A2 | Number of Participants With Adverse Events (AEs) | Immune-mediated AEs (Pneumonitis) | 2 Participants |
| Arm A2 | Number of Participants With Adverse Events (AEs) | Immune-mediated AEs (Rash) | 5 Participants |
| Arm A2 | Number of Participants With Adverse Events (AEs) | Serious Adverse Events (SAEs) | 37 Participants |
| Arm B | Number of Participants With Adverse Events (AEs) | Immune-mediated AEs (Hypersensitivity/Infusion Reactions) | 1 Participants |
| Arm B | Number of Participants With Adverse Events (AEs) | Adverse Events (AEs) | 83 Participants |
| Arm B | Number of Participants With Adverse Events (AEs) | Serious Adverse Events (SAEs) | 41 Participants |
| Arm B | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation | 33 Participants |
| Arm B | Number of Participants With Adverse Events (AEs) | Immune-mediated AEs (Pneumonitis) | 8 Participants |
| Arm B | Number of Participants With Adverse Events (AEs) | Immune-mediated AEs (Diarrhea/Colitis) | 1 Participants |
| Arm B | Number of Participants With Adverse Events (AEs) | Immune-mediated AEs (Hepatitis) | 3 Participants |
| Arm B | Number of Participants With Adverse Events (AEs) | Immune-mediated AEs (Nephritis/Renal Dysfunction) | 0 Participants |
| Arm B | Number of Participants With Adverse Events (AEs) | Immune-mediated AEs (Rash) | 9 Participants |
| Arm C | Number of Participants With Adverse Events (AEs) | Immune-mediated AEs (Nephritis/Renal Dysfunction) | 0 Participants |
| Arm C | Number of Participants With Adverse Events (AEs) | Immune-mediated AEs (Diarrhea/Colitis) | 0 Participants |
| Arm C | Number of Participants With Adverse Events (AEs) | Immune-mediated AEs (Pneumonitis) | 0 Participants |
| Arm C | Number of Participants With Adverse Events (AEs) | Adverse Events (AEs) | 49 Participants |
| Arm C | Number of Participants With Adverse Events (AEs) | Immune-mediated AEs (Rash) | 10 Participants |
| Arm C | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation | 18 Participants |
| Arm C | Number of Participants With Adverse Events (AEs) | Serious Adverse Events (SAEs) | 20 Participants |
| Arm C | Number of Participants With Adverse Events (AEs) | Immune-mediated AEs (Hepatitis) | 2 Participants |
| Arm C | Number of Participants With Adverse Events (AEs) | Immune-mediated AEs (Hypersensitivity/Infusion Reactions) | 3 Participants |
Secondary
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
Time frame: From first dose to up to 30 days post last dose (up to 34 months)
Population: All treated participant with at least one on-treatment measurement of the corresponding laboratory parameter
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A1 | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | ALT or AST > 3xULN | 19 Participants |
| Arm A1 | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | ALT or AST > 5xULN | 11 Participants |
| Arm A1 | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | ALT or AST > 10xULN | 2 Participants |
| Arm A1 | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | ALT or AST > 20xULN | 0 Participants |
| Arm A1 | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | TOTAL BILIRUBIN > 2xULN | 3 Participants |
| Arm A1 | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | ALP > 1.5xULN | 49 Participants |
| Arm A1 | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | Concurrent ALT or AST elevation > 3xULN with total Bilirubin > 1.5xULN within one day | 3 Participants |
| Arm A1 | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | Concurrent ALT or AST elevation > 3xULN with total Bilirubin > 1.5xULN within 30 days | 4 Participants |
| Arm A1 | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | Concurrent ALT or AST elevation > 3xULN with total Bilirubin > 2xULN within one day | 2 Participants |
| Arm A1 | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | Concurrent ALT or AST elevation > 3xULN with total Bilirubin > 2xULN within 30 days | 2 Participants |
| Arm A2 | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | ALT or AST > 10xULN | 5 Participants |
| Arm A2 | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | Concurrent ALT or AST elevation > 3xULN with total Bilirubin > 2xULN within one day | 1 Participants |
| Arm A2 | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | ALT or AST > 20xULN | 1 Participants |
| Arm A2 | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | TOTAL BILIRUBIN > 2xULN | 1 Participants |
| Arm A2 | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | ALP > 1.5xULN | 34 Participants |
| Arm A2 | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | Concurrent ALT or AST elevation > 3xULN with total Bilirubin > 1.5xULN within one day | 1 Participants |
| Arm A2 | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | Concurrent ALT or AST elevation > 3xULN with total Bilirubin > 2xULN within 30 days | 1 Participants |
| Arm A2 | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | Concurrent ALT or AST elevation > 3xULN with total Bilirubin > 1.5xULN within 30 days | 1 Participants |
| Arm A2 | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | ALT or AST > 3xULN | 23 Participants |
| Arm A2 | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | ALT or AST > 5xULN | 14 Participants |
| Arm B | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | Concurrent ALT or AST elevation > 3xULN with total Bilirubin > 1.5xULN within 30 days | 0 Participants |
| Arm B | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | Concurrent ALT or AST elevation > 3xULN with total Bilirubin > 1.5xULN within one day | 0 Participants |
| Arm B | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | Concurrent ALT or AST elevation > 3xULN with total Bilirubin > 2xULN within 30 days | 0 Participants |
| Arm B | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | ALT or AST > 3xULN | 6 Participants |
| Arm B | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | ALT or AST > 20xULN | 1 Participants |
| Arm B | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | ALP > 1.5xULN | 34 Participants |
| Arm B | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | Concurrent ALT or AST elevation > 3xULN with total Bilirubin > 2xULN within one day | 0 Participants |
| Arm B | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | ALT or AST > 5xULN | 3 Participants |
| Arm B | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | TOTAL BILIRUBIN > 2xULN | 1 Participants |
| Arm B | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | ALT or AST > 10xULN | 1 Participants |
| Arm C | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | TOTAL BILIRUBIN > 2xULN | 0 Participants |
| Arm C | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | Concurrent ALT or AST elevation > 3xULN with total Bilirubin > 1.5xULN within 30 days | 1 Participants |
| Arm C | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | ALP > 1.5xULN | 21 Participants |
| Arm C | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | Concurrent ALT or AST elevation > 3xULN with total Bilirubin > 2xULN within 30 days | 0 Participants |
| Arm C | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | Concurrent ALT or AST elevation > 3xULN with total Bilirubin > 1.5xULN within one day | 1 Participants |
| Arm C | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | ALT or AST > 5xULN | 3 Participants |
| Arm C | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | ALT or AST > 10xULN | 0 Participants |
| Arm C | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | ALT or AST > 20xULN | 0 Participants |
| Arm C | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | ALT or AST > 3xULN | 4 Participants |
| Arm C | Number of Participants With Laboratory Abnormalities in Specific Liver Tests | Concurrent ALT or AST elevation > 3xULN with total Bilirubin > 2xULN within one day | 0 Participants |
Secondary
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
Time frame: From first dose to up to 30 days post last dose (Up to 34 months)
Population: All treated participants with thyroid stimulating hormone (TSH) abnormality
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A1 | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN | 22 Participants |
| Arm A1 | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN with TSH <= ULN at baseline | 17 Participants |
| Arm A1 | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN with at least one FT3/FT4 test value < LLN | 10 Participants |
| Arm A1 | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN with all other FT3/FT4 test values >= LLN | 10 Participants |
| Arm A1 | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN with FT3/FT4 test missing | 2 Participants |
| Arm A1 | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN | 16 Participants |
| Arm A1 | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN with TSH >= LLN at baseline | 13 Participants |
| Arm A1 | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN with at least one FT3/FT4 test value > ULN | 5 Participants |
| Arm A1 | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN with all other FT3/FT4 test values <= ULN | 8 Participants |
| Arm A1 | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN with FT3/FT4 test missing | 3 Participants |
| Arm A2 | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN with at least one FT3/FT4 test value < LLN | 6 Participants |
| Arm A2 | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN with all other FT3/FT4 test values <= ULN | 4 Participants |
| Arm A2 | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN with all other FT3/FT4 test values >= LLN | 9 Participants |
| Arm A2 | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN with FT3/FT4 test missing | 2 Participants |
| Arm A2 | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN | 12 Participants |
| Arm A2 | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN with TSH >= LLN at baseline | 11 Participants |
| Arm A2 | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN with FT3/FT4 test missing | 3 Participants |
| Arm A2 | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN with at least one FT3/FT4 test value > ULN | 5 Participants |
| Arm A2 | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN | 17 Participants |
| Arm A2 | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN with TSH <= ULN at baseline | 12 Participants |
| Arm B | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN with at least one FT3/FT4 test value > ULN | 2 Participants |
| Arm B | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN with TSH >= LLN at baseline | 19 Participants |
| Arm B | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN with FT3/FT4 test missing | 12 Participants |
| Arm B | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN | 12 Participants |
| Arm B | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN with all other FT3/FT4 test values >= LLN | 3 Participants |
| Arm B | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN | 25 Participants |
| Arm B | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN with all other FT3/FT4 test values <= ULN | 11 Participants |
| Arm B | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN with TSH <= ULN at baseline | 7 Participants |
| Arm B | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN with FT3/FT4 test missing | 2 Participants |
| Arm B | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN with at least one FT3/FT4 test value < LLN | 7 Participants |
| Arm C | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN with FT3/FT4 test missing | 2 Participants |
| Arm C | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN with at least one FT3/FT4 test value > ULN | 7 Participants |
| Arm C | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN | 8 Participants |
| Arm C | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN with FT3/FT4 test missing | 1 Participants |
| Arm C | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN with TSH >= LLN at baseline | 8 Participants |
| Arm C | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN with TSH <= ULN at baseline | 12 Participants |
| Arm C | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN with at least one FT3/FT4 test value < LLN | 5 Participants |
| Arm C | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN with all other FT3/FT4 test values >= LLN | 10 Participants |
| Arm C | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN | 17 Participants |
| Arm C | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN with all other FT3/FT4 test values <= ULN | 0 Participants |
Secondary
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
Time frame: From first dose to up to 30 days post last dose (Up to 34 months)
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A1 | Number of Participants With Laboratory Values Change From Baseline | Neutrophil Grade 2 | 1 Participants |
| Arm A1 | Number of Participants With Laboratory Values Change From Baseline | Leukocytes Grade 2 | 1 Participants |
| Arm A1 | Number of Participants With Laboratory Values Change From Baseline | Hemoglobin Grade 2 | 8 Participants |
| Arm A1 | Number of Participants With Laboratory Values Change From Baseline | Neutrophil Grade 1 | 3 Participants |
| Arm A1 | Number of Participants With Laboratory Values Change From Baseline | Lymphocytes Grade 0 | 24 Participants |
| Arm A1 | Number of Participants With Laboratory Values Change From Baseline | Creatinine Grade 1 | 7 Participants |
| Arm A1 | Number of Participants With Laboratory Values Change From Baseline | Neutrophil Grade 0 | 35 Participants |
| Arm A1 | Number of Participants With Laboratory Values Change From Baseline | Lymphocytes Grade 3 | 1 Participants |
| Arm A1 | Number of Participants With Laboratory Values Change From Baseline | Lymphocytes Grade 1 | 10 Participants |
| Arm A1 | Number of Participants With Laboratory Values Change From Baseline | Bilirubin Grade 0 | 4 Participants |
| Arm A1 | Number of Participants With Laboratory Values Change From Baseline | Lymphocytes Grade 2 | 3 Participants |
| Arm A1 | Number of Participants With Laboratory Values Change From Baseline | Alanine Aminotransferase Grade 1 | 4 Participants |
| Arm A1 | Number of Participants With Laboratory Values Change From Baseline | Platelet Grade 0 | 35 Participants |
| Arm A1 | Number of Participants With Laboratory Values Change From Baseline | Hemoglobin Grade 1 | 38 Participants |
| Arm A1 | Number of Participants With Laboratory Values Change From Baseline | Alanine Aminotransferase Grade 0 | 47 Participants |
| Arm A1 | Number of Participants With Laboratory Values Change From Baseline | Aspartate Aminotransferase Grade 1 | 5 Participants |
| Arm A1 | Number of Participants With Laboratory Values Change From Baseline | Platelet Grade 1 | 4 Participants |
| Arm A1 | Number of Participants With Laboratory Values Change From Baseline | Bilirubin Grade 1 | 1 Participants |
| Arm A1 | Number of Participants With Laboratory Values Change From Baseline | Aspartate Aminotransferase Grade 0 | 52 Participants |
| Arm A1 | Number of Participants With Laboratory Values Change From Baseline | Alkaline Phosphatase Grade 3 | 1 Participants |
| Arm A1 | Number of Participants With Laboratory Values Change From Baseline | Leukocytes Grade 0 | 38 Participants |
| Arm A1 | Number of Participants With Laboratory Values Change From Baseline | Creatinine Grade 0 | 30 Participants |
| Arm A1 | Number of Participants With Laboratory Values Change From Baseline | Alkaline Phosphatase Grade 2 | 9 Participants |
| Arm A1 | Number of Participants With Laboratory Values Change From Baseline | Alkaline Phosphatase Grade 1 | 13 Participants |
| Arm A1 | Number of Participants With Laboratory Values Change From Baseline | Leukocytes Grade 1 | 10 Participants |
| Arm A1 | Number of Participants With Laboratory Values Change From Baseline | Hemoglobin Grade 0 | 23 Participants |
| Arm A1 | Number of Participants With Laboratory Values Change From Baseline | Alkaline Phosphatase Grade 0 | 25 Participants |
| Arm A2 | Number of Participants With Laboratory Values Change From Baseline | Bilirubin Grade 0 | 12 Participants |
| Arm A2 | Number of Participants With Laboratory Values Change From Baseline | Hemoglobin Grade 0 | 21 Participants |
| Arm A2 | Number of Participants With Laboratory Values Change From Baseline | Hemoglobin Grade 1 | 28 Participants |
| Arm A2 | Number of Participants With Laboratory Values Change From Baseline | Hemoglobin Grade 2 | 3 Participants |
| Arm A2 | Number of Participants With Laboratory Values Change From Baseline | Platelet Grade 0 | 32 Participants |
| Arm A2 | Number of Participants With Laboratory Values Change From Baseline | Platelet Grade 1 | 1 Participants |
| Arm A2 | Number of Participants With Laboratory Values Change From Baseline | Leukocytes Grade 0 | 34 Participants |
| Arm A2 | Number of Participants With Laboratory Values Change From Baseline | Leukocytes Grade 1 | 6 Participants |
| Arm A2 | Number of Participants With Laboratory Values Change From Baseline | Leukocytes Grade 2 | 0 Participants |
| Arm A2 | Number of Participants With Laboratory Values Change From Baseline | Lymphocytes Grade 0 | 30 Participants |
| Arm A2 | Number of Participants With Laboratory Values Change From Baseline | Lymphocytes Grade 1 | 8 Participants |
| Arm A2 | Number of Participants With Laboratory Values Change From Baseline | Lymphocytes Grade 2 | 3 Participants |
| Arm A2 | Number of Participants With Laboratory Values Change From Baseline | Lymphocytes Grade 3 | 0 Participants |
| Arm A2 | Number of Participants With Laboratory Values Change From Baseline | Neutrophil Grade 0 | 26 Participants |
| Arm A2 | Number of Participants With Laboratory Values Change From Baseline | Neutrophil Grade 1 | 4 Participants |
| Arm A2 | Number of Participants With Laboratory Values Change From Baseline | Alkaline Phosphatase Grade 0 | 33 Participants |
| Arm A2 | Number of Participants With Laboratory Values Change From Baseline | Alkaline Phosphatase Grade 1 | 4 Participants |
| Arm A2 | Number of Participants With Laboratory Values Change From Baseline | Alkaline Phosphatase Grade 2 | 1 Participants |
| Arm A2 | Number of Participants With Laboratory Values Change From Baseline | Alkaline Phosphatase Grade 3 | 3 Participants |
| Arm A2 | Number of Participants With Laboratory Values Change From Baseline | Aspartate Aminotransferase Grade 0 | 49 Participants |
| Arm A2 | Number of Participants With Laboratory Values Change From Baseline | Aspartate Aminotransferase Grade 1 | 4 Participants |
| Arm A2 | Number of Participants With Laboratory Values Change From Baseline | Alanine Aminotransferase Grade 0 | 48 Participants |
| Arm A2 | Number of Participants With Laboratory Values Change From Baseline | Alanine Aminotransferase Grade 1 | 3 Participants |
| Arm A2 | Number of Participants With Laboratory Values Change From Baseline | Creatinine Grade 0 | 30 Participants |
| Arm A2 | Number of Participants With Laboratory Values Change From Baseline | Creatinine Grade 1 | 5 Participants |
| Arm B | Number of Participants With Laboratory Values Change From Baseline | Aspartate Aminotransferase Grade 1 | 6 Participants |
| Arm B | Number of Participants With Laboratory Values Change From Baseline | Alkaline Phosphatase Grade 1 | 13 Participants |
| Arm B | Number of Participants With Laboratory Values Change From Baseline | Platelet Grade 0 | 10 Participants |
| Arm B | Number of Participants With Laboratory Values Change From Baseline | Hemoglobin Grade 0 | 30 Participants |
| Arm B | Number of Participants With Laboratory Values Change From Baseline | Alanine Aminotransferase Grade 0 | 13 Participants |
| Arm B | Number of Participants With Laboratory Values Change From Baseline | Neutrophil Grade 1 | 1 Participants |
| Arm B | Number of Participants With Laboratory Values Change From Baseline | Creatinine Grade 0 | 13 Participants |
| Arm B | Number of Participants With Laboratory Values Change From Baseline | Creatinine Grade 1 | 5 Participants |
| Arm B | Number of Participants With Laboratory Values Change From Baseline | Alanine Aminotransferase Grade 1 | 3 Participants |
| Arm B | Number of Participants With Laboratory Values Change From Baseline | Alkaline Phosphatase Grade 3 | 0 Participants |
| Arm B | Number of Participants With Laboratory Values Change From Baseline | Leukocytes Grade 1 | 4 Participants |
| Arm B | Number of Participants With Laboratory Values Change From Baseline | Lymphocytes Grade 1 | 0 Participants |
| Arm B | Number of Participants With Laboratory Values Change From Baseline | Hemoglobin Grade 2 | 2 Participants |
| Arm B | Number of Participants With Laboratory Values Change From Baseline | Lymphocytes Grade 2 | 5 Participants |
| Arm B | Number of Participants With Laboratory Values Change From Baseline | Platelet Grade 1 | 0 Participants |
| Arm B | Number of Participants With Laboratory Values Change From Baseline | Leukocytes Grade 0 | 28 Participants |
| Arm B | Number of Participants With Laboratory Values Change From Baseline | Aspartate Aminotransferase Grade 0 | 28 Participants |
| Arm B | Number of Participants With Laboratory Values Change From Baseline | Lymphocytes Grade 3 | 0 Participants |
| Arm B | Number of Participants With Laboratory Values Change From Baseline | Lymphocytes Grade 0 | 28 Participants |
| Arm B | Number of Participants With Laboratory Values Change From Baseline | Bilirubin Grade 0 | 2 Participants |
| Arm B | Number of Participants With Laboratory Values Change From Baseline | Neutrophil Grade 0 | 37 Participants |
| Arm B | Number of Participants With Laboratory Values Change From Baseline | Alkaline Phosphatase Grade 0 | 13 Participants |
| Arm B | Number of Participants With Laboratory Values Change From Baseline | Leukocytes Grade 2 | 1 Participants |
| Arm B | Number of Participants With Laboratory Values Change From Baseline | Alkaline Phosphatase Grade 2 | 2 Participants |
| Arm B | Number of Participants With Laboratory Values Change From Baseline | Hemoglobin Grade 1 | 20 Participants |
| Arm C | Number of Participants With Laboratory Values Change From Baseline | Alanine Aminotransferase Grade 0 | 4 Participants |
| Arm C | Number of Participants With Laboratory Values Change From Baseline | Leukocytes Grade 1 | 2 Participants |
| Arm C | Number of Participants With Laboratory Values Change From Baseline | Neutrophil Grade 2 | 1 Participants |
| Arm C | Number of Participants With Laboratory Values Change From Baseline | Bilirubin Grade 1 | 0 Participants |
| Arm C | Number of Participants With Laboratory Values Change From Baseline | Alkaline Phosphatase Grade 0 | 8 Participants |
| Arm C | Number of Participants With Laboratory Values Change From Baseline | Leukocytes Grade 0 | 13 Participants |
| Arm C | Number of Participants With Laboratory Values Change From Baseline | Alkaline Phosphatase Grade 1 | 6 Participants |
| Arm C | Number of Participants With Laboratory Values Change From Baseline | Creatinine Grade 1 | 2 Participants |
| Arm C | Number of Participants With Laboratory Values Change From Baseline | Alkaline Phosphatase Grade 2 | 0 Participants |
| Arm C | Number of Participants With Laboratory Values Change From Baseline | Platelet Grade 1 | 0 Participants |
| Arm C | Number of Participants With Laboratory Values Change From Baseline | Alkaline Phosphatase Grade 3 | 0 Participants |
| Arm C | Number of Participants With Laboratory Values Change From Baseline | Creatinine Grade 0 | 3 Participants |
| Arm C | Number of Participants With Laboratory Values Change From Baseline | Aspartate Aminotransferase Grade 0 | 9 Participants |
| Arm C | Number of Participants With Laboratory Values Change From Baseline | Platelet Grade 0 | 13 Participants |
| Arm C | Number of Participants With Laboratory Values Change From Baseline | Hemoglobin Grade 0 | 8 Participants |
| Arm C | Number of Participants With Laboratory Values Change From Baseline | Aspartate Aminotransferase Grade 1 | 4 Participants |
| Arm C | Number of Participants With Laboratory Values Change From Baseline | Hemoglobin Grade 2 | 2 Participants |
| Arm C | Number of Participants With Laboratory Values Change From Baseline | Alanine Aminotransferase Grade 1 | 1 Participants |
| Arm C | Number of Participants With Laboratory Values Change From Baseline | Lymphocytes Grade 1 | 2 Participants |
| Arm C | Number of Participants With Laboratory Values Change From Baseline | Lymphocytes Grade 2 | 3 Participants |
| Arm C | Number of Participants With Laboratory Values Change From Baseline | Lymphocytes Grade 0 | 14 Participants |
| Arm C | Number of Participants With Laboratory Values Change From Baseline | Hemoglobin Grade 1 | 12 Participants |
| Arm C | Number of Participants With Laboratory Values Change From Baseline | Neutrophil Grade 0 | 7 Participants |
| Arm C | Number of Participants With Laboratory Values Change From Baseline | Bilirubin Grade 0 | 3 Participants |
Secondary
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
Time frame: Up to approximately 36 months
Secondary
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
Time frame: Up to approximately 36 months
Secondary
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
Time frame: Up to approximately 36 months
Secondary
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
Time frame: Up to approximately 36 months