Metastatic Castration-resistant Prostate Cancer
Conditions
Keywords
Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1(PDL1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)
Brief summary
This is a study of pembrolizumab (MK-3475) in participants with metastatic castration-resistant prostate cancer (mCRPC). Participants will be enrolled into one of five cohorts: Cohort 1 (participants with programmed cell death ligand 1 \[PD-L1\]-positive, measurable disease), Cohort 2 (participants with PD-L1 negative, measurable disease), Cohort 3 (participants with bone-metastases and non-measurable disease) post-chemotherapy, Cohort 4 (participants with Response Evaluation Criteria in Solid Tumors version 1.1- \[RECIST 1.1\]-measureable disease) and Cohort 5 (participants with bone metastases only or bone-predominant disease) pre-chemotherapy.
Detailed description
Participants with mCRPC previously treated with docetaxel-based chemotherapy in Cohorts 1 to 3 will receive monotherapy with pembrolizumab. Chemotherapy-naïve subjects with mCRPC either having failed or showing signs of failure with enzalutamide in Cohorts 4 and 5 will receive pembrolizumab monotherapy in addition to their current regimen of enzalutamide. In all cohorts, pembrolizumab administration will occur on Day 1 of each 3-week dosing cycle and will continue for a maximum of 35 cycles (approximately 2 years) unless specific withdrawal/discontinuation criteria are met. Participants who discontinue after 35 infusions of pembrolizumab for reasons other than disease progression or intolerability, or who discontinue after attaining a complete response may be eligible for up to 17 additional infusions (approximately 1 year) after they have experienced disease progression.
Interventions
BIOLOGICALPembrolizumab
Intravenous infusion
Sponsors
Merck Sharp & Dohme LLC
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
* Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology. Disease must be either metastatic or locally confined inoperable disease that cannot be treated with definitive intent (no chance for a curative intervention). * Has supplied tumor tissue from a newly obtained biopsy or a biopsy obtained ≤12 months prior to study start and an archival specimen, if available, from a site not previously irradiated. Participants in Cohorts 1, 2, and 4 with visceral/measurable lesions must provide a newly obtained biopsy performed after the last line of systemic therapy or a biopsy obtained ≤12 months prior to study start and an archival specimen, if available. Participants in Cohorts 3 and 5 must at least provide an archival specimen. For Cohorts 1, 2, and 3 only: * Has been treated with: * At least 1 targeted endocrine therapy (defined as second generation antiandrogen therapies that include but are not limited to abiraterone acetate with prednisone, enzalutamide, and next generation targeted agents such as ARN-509). * At least 1 regimen/line of chemotherapy that contained docetaxel. * No more than 2 chemotherapy regimens. * No more than 3 regimens/lines of the aforementioned treatments (having failed/progressed on chemotherapy and targeted endocrine therapy). For Cohorts 4 and 5 only: * Failing or showing early signs of failure on current pre-chemotherapy enzalutamide treatment as defined by Prostate Cancer Working Group 3 (PCWG3) guidelines. Participants can have failed prior abiraterone treatment before current enzalutamide treatment. Participants must have had a clinically meaningful response to enzalutamide treatment. Enzalutamide must have been initiated no less than 4 weeks prior to the first dose of trial treatment and be continued throughout the study. For All Cohorts: * Has documented prostate cancer progression within 6 months prior to screening, as determined by the Investigator, by means of one of the following: 1) PSA progression as defined by a minimum of 3 rising PSA levels with an interval of ≥1 week between each assessment where the PSA value at screening should be ≥2 ng/mL, OR, 2) Radiographic disease progression in soft tissue or bone with or without PSA progression * Has ongoing androgen deprivation with total serum testosterone \<50 ng/dL (\<2.0 nM). * Participants receiving bone resorptive therapy (including but not limited to bisphosphonate or Receptor activator of nuclear factor kappa-B ligand \[RANK-L inhibitor\]) must have been on stable doses for ≥4 weeks prior to first dose of study drug. * Has a performance status of 0, 1 or 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale * Participants of reproductive potential must agree to use an adequate method of contraception, starting with the first dose of study drug through at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception after the last dose of enzalutamide is 30 days. * Demonstrates adequate organ function.
Exclusion criteria
For All Cohorts: * Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of study drug. * Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. * Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to the first dose of study drug or who has not recovered (i.e., ≤ Grade 1 or at Baseline) from AEs due to mAbs administered more than 4 weeks earlier. * Has had prior chemotherapy, targeted small molecule therapy, or external beam radiation therapy within 4 weeks prior to the first dose of study drug or who has not recovered (i.e., ≤ Grade 1 or at Baseline) from AEs due to a previously administered agent. * Has a known additional malignancy that has had progression or has required active treatment in the last 3 years. Exceptions include basal cell carcinoma of the skin and squamous cell carcinoma of the skin that has undergone potentially curative therapy. * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. * Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). * Has evidence of interstitial lung disease and/or a history of (non-infectious) pneumonitis that required steroids, or current pneumonitis. * Has an active infection requiring systemic therapy. * Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. * Has previously participated in any other pembrolizumab (MK-3475) trial, or received prior therapy with an anti-programmed cell death 1 (anti-PD-1, anti-PD ligand 1 \[anti-PD-L1\], and anti-PD-L2 \[including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways\]). * Has a known history of Human Immunodeficiency Virus (HIV). * Has known active Hepatitis B or Hepatitis C. * Has received a live vaccine within 30 days of planned start of study drug. Any licensed coronavirus disease 2019 (COVID-19) vaccine (including for Emergency use) in a particular country is allowed in the study as long as they are messenger ribonucleic acid (mRNA) vaccines, adenoviral vaccines, or inactivated vaccines. Investigational vaccines (ie, those not licensed or approved for Emergency Use) are not allowed. For Cohorts 4 and 5 only: * Has received prior chemotherapy (e.g., docetaxel) for mCPRC. * Has any condition (cardiac, neurologic, absorption) other than clinically failing or showing early signs of failure on enzalutamide treatment that would require imminent discontinuation of enzalutamide treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (Cohort 1, Cohort 2, Cohort 4 and Cohorts 1 and 2 Combined) | Up to ~52 months | ORR was defined as the percentage of participants who experienced a complete response (CR; disappearance of all target lesions) or a partial response (PR; at least a 30% decrease in the sum of diameters of target lesions) and was assessed using RECIST 1.1 by central imaging vendor. Per protocol, analysis for this outcome measure was conducted in Cohorts 1 and 2 combined, as well as in Cohorts 1, 2, and 4 separately for the first course of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Discontinued Study Treatment Due to an AE | Up to ~52 months | An AE was defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The percentage of participants who discontinued study treatment during the first course of treatment due to an AE was reported. |
| Disease Control Rate (DCR) (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, Cohorts 4 and 5 Combined) | Up to ~52 months | Percentage of participants who had CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions)or stable disease (SD; Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease) for at least 6 months, by central imaging vendor where progressive disease (PD) in bone-only tumors were determined by radionuclide bone scan using Prostate Cancer Working Group (PCWG3) criteria and PD for all other tumors was determined using RECIST 1.1. Per protocol, analysis for this outcome measure was conducted in Cohorts 1 and 2 combined, Cohorts 1,2, and 3 combined, Cohorts 4 and 5 combined well as in Cohorts 1 to 5 separately for the first course of treatment. |
| Duration of Response (DOR) Per PCWG3-modified RECIST 1.1 (Cohort 1, Cohort 2, Cohort 4 and Cohorts 1 and 2 Combined) | Up to ~52 months | DOR was defined as the time from first documented evidence of complete response (CR; disappearance of all target lesions) or partial response (PR; ≥30% decrease in the sum of diameters of target lesions) until progressive disease (PD) assessed by central imaging where PD was determined by radionuclide bone scan using Prostate Cancer Working Group (PCWG3)-modified RECIST 1.1 criteria and PD for all other tumors was determined using RECIST 1.1 or death due to any cause, whichever occurred first. Per protocol, analysis for this outcome measure was conducted in Cohorts 1, 2 and 4 separately, well as in Cohorts 1 and 2 combined for the first course of treatment. |
| DOR- Per RECIST 1.1 (Cohort 1, Cohort 2, Cohort 4 and Cohorts 1 and 2 Combined) | Up to ~52 months | DOR was defined as the time from first documented evidence of complete response (CR; disappearance of all target lesions) or partial response (PR; ≥30% decrease in the sum of diameters of target lesions) ) until progressive disease (PD) assessed by central imaging where PD was determined by radionuclide bone scan using RECIST 1.1 and PD for all other tumors was determined using RECIST 1.1 or death due to any cause, whichever occurred first. Per protocol, analysis for this outcome measure was conducted in Cohorts 1, 2 and 4 separately, well as in Cohorts 1 and 2 combined for the first course of treatment. |
| Prostate-specific Antigen (PSA) Response Rate (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined and Cohorts 4 and 5 Combined) | Up to ~52 months | Percentage of participants who had PSA response defined as at least 50% decline from baseline measured twice at least 3 weeks apart. Per protocol, analysis for this outcome measure was conducted in Cohorts 1 and 2 combined, Cohorts 1, 2, and 3 combined, Cohorts 4 and 5 combined well as in Cohorts 1 to 5 for the first course of treatment. |
| Time to PSA Progression (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined and Cohorts 4 and 5 Combined) | Up to ~52 months | Time to PSA progression was defined as the time from first day of study treatment to the date of PSA progression. Participants without PSA progression were censored at the last PSA assessment date. PSA progression was defined as the date that an increase of 25% or more and an absolute increase of 2 ng/mL or more from the nadir were documented. For participants who had a decline in PSA during treatment, PSA progression must have been confirmed by a second value 3 or more weeks later increased with respect to the nadir PSA. Per protocol, analysis for this outcome measure was conducted in Cohorts 1 and 2 combined, Cohorts 1,2, and 3 combined, Cohorts 4 and 5 combined well as in Cohorts 1 to 5 separately for the first course of treatment. |
| Percentage of Participants Who Experienced an Adverse Event (AE) | Up to ~52 months | An AE was defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The percentage of participants that experienced at least one AE for the first course of treatment was reported. |
| Overall Survival (OS) (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, Cohorts 4 and 5 Combined) | Up to ~52 months | OS was defined as the time from first day of study treatment to the time of death. Participants without documented death were censored at the date of the last follow up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. Per protocol, analysis for this outcome measure was conducted in Cohorts 1 and 2 combined, Cohorts 1,2, and 3 combined, Cohorts 4 and 5 combined well as in Cohorts 1 to 5 separately for the first course of treatment. |
| Duration of PSA Response (Cohorts 4 and 5 by Cohort and Combined) | Up to ~52 months | Duration of PSA response was defined as the time from PSA response, when the PSA value first declined by at least 50% of the baseline (must have been confirmed by a second value), to the date of PSA progression at which there was an increase of 25% or more from the nadir PSA, provided the absolute increase from the nadir PSA was at least 2 ng/mL. Per protocol, analysis for this outcome measure was conducted in Cohorts 4 and 5 separately and combined for the first course of treatment. |
| Time to Initiation of Cytotoxic Chemotherapy (Cohorts 4 and 5 by Cohort and Combined) | Up to ~52 months | Time to initiation of cytotoxic chemotherapy was defined as the time from first day of study treatment to the time of initiation of cytotoxic chemotherapy for prostate cancer. The median time was calculated using the Kaplan-Meier method for censored data. Per protocol, analysis for this outcome measure was conducted in Cohorts 4 and 5 separately and combined for the first course of treatment. |
| Time to New-Anticancer Therapy (Cohorts 4 and 5 By Cohort and Combined) | Up to ~52 months | Time to new-anticancer therapy was defined as the time from first day of study treatment to the time of new-anticancer therapy for prostate cancer. The median time was calculated using the Kaplan-Meier method for censored data. Per protocol, analysis for this outcome measure was conducted in Cohorts 4 and 5 separately and combined for the first course of treatment. |
| Time to First Skeletal-related Event (Cohorts 4 and 5 By Cohort and Combined) | Up to ~52 months | Time to initiation of first skeletal-related event was defined as the time from first day of study treatment to the first skeletal-related event, which was defined as radiation therapy or surgery to bone, pathologic bone fracture, spinal cord compression, or change or antineoplastic therapy to treat bone pain. Per protocol, analysis for this outcome measure was conducted in Cohorts 4 and 5 separately and combined for the first course of treatment. |
| Radiographic Progression-free Survival (rPFS) - Per PCWG3-modified RECIST 1.1 (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, and Cohorts 4 and 5 Combined) | Up to ~52 months | rPFS was defined as the time from first day of study treatment to the documented disease progression by central imaging vendor where PD in bone-only tumors was determined by radionuclide bone scan using PCWG3 criteria and PD for all other tumors were determined using RECIST 1.1 or death due to any cause, whichever occurs first. Per protocol, analysis for this outcome measure was conducted in Cohorts 1 and 2 combined, Cohorts 1,2, and 3 combined, Cohorts 4 and 5 combined well as in Cohorts 1 to 5 separately for the first course of treatment. |
Participant flow
Pre-assignment details
Male participants at least 18 years of age with Metastatic Castration-resistant Prostate Cancer (mCRPC) were screened for enrollment in the study. Per protocol, response/progression or adverse events (AEs) that occurred during the second course were not counted towards efficacy outcome measures or safety outcome measures, respectively.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: PD-L1 Positive With Measurable Disease Participants with PD-L1-positive, measurable disease received pembrolizumab 200 mg via IV infusion on Day 1 of every 3-week cycle for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab with SD or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion. | 133 |
| Cohort 2: PD-L1 Negative With Measurable Disease Participants with PD-L1 negative, measurable disease received pembrolizumab 200 mg via IV infusion on Day 1 of every 3-week cycle for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion. | 69 |
| Cohort 3: Bone Metastases With Non-measurable Disease Participants with bone metastases and non-measurable disease received pembrolizumab 200 mg via IV infusion on Day 1 of every 3-week cycle for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion. | 58 |
| Cohort 4: RECIST 1.1-measureable Disease Participants with RECIST 1.1-measureable disease received pembrolizumab 200 mg via IV infusion on Day 1 of every 3-week cycle for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab with SD or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion. | 81 |
| Cohort 5: Bone Metastases Only or Bone-predominant Disease Participants with bone metastases only or bone-predominant disease received pembrolizumab 200 mg via IV infusion on Day 1 of every 3-week cycle for up to 2 years. Eligible participants who stopped the initial course of pembrolizumab with SD or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion. | 47 |
| Total | 388 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 24 | 9 | 9 | 7 | 2 |
| Overall Study | Death | 100 | 53 | 48 | 69 | 38 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Screen Failure | 0 | 2 | 0 | 0 | 1 |
| Overall Study | Sponsor Decision | 7 | 4 | 0 | 4 | 5 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Cohort 1: PD-L1 Positive With Measurable Disease | Cohort 2: PD-L1 Negative With Measurable Disease | Cohort 3: Bone Metastases With Non-measurable Disease | Cohort 4: RECIST 1.1-measureable Disease | Cohort 5: Bone Metastases Only or Bone-predominant Disease | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 67.9 years STANDARD_DEVIATION 7.6 | 68.6 years STANDARD_DEVIATION 7.2 | 69.4 years STANDARD_DEVIATION 7.1 | 73.1 years STANDARD_DEVIATION 8.4 | 69.7 years STANDARD_DEVIATION 9.5 | 69.5 years STANDARD_DEVIATION 8.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 4 Participants | 1 Participants | 3 Participants | 3 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 121 Participants | 55 Participants | 55 Participants | 76 Participants | 44 Participants | 351 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 9 Participants | 10 Participants | 2 Participants | 2 Participants | 0 Participants | 23 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 13 Participants | 6 Participants | 7 Participants | 5 Participants | 2 Participants | 33 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 1 Participants | 1 Participants | 3 Participants | 3 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants | 10 Participants | 2 Participants | 2 Participants | 0 Participants | 22 Participants |
| Race (NIH/OMB) White | 109 Participants | 52 Participants | 48 Participants | 70 Participants | 42 Participants | 321 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 133 Participants | 69 Participants | 58 Participants | 81 Participants | 47 Participants | 388 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 126 / 133 | 63 / 69 | 57 / 58 | 76 / 81 | 40 / 47 | 0 / 1 |
| other Total, other adverse events | 128 / 133 | 62 / 67 | 57 / 58 | 79 / 81 | 42 / 45 | 1 / 1 |
| serious Total, serious adverse events | 70 / 133 | 28 / 67 | 25 / 58 | 26 / 81 | 19 / 45 | 0 / 1 |
Outcome results
Primary
Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (Cohort 1, Cohort 2, Cohort 4 and Cohorts 1 and 2 Combined)
ORR was defined as the percentage of participants who experienced a complete response (CR; disappearance of all target lesions) or a partial response (PR; at least a 30% decrease in the sum of diameters of target lesions) and was assessed using RECIST 1.1 by central imaging vendor. Per protocol, analysis for this outcome measure was conducted in Cohorts 1 and 2 combined, as well as in Cohorts 1, 2, and 4 separately for the first course of treatment.
Time frame: Up to ~52 months
Population: Analysis population was the All Subjects as Treated (ASaT) which consisted of all allocated participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: PD-L1 Positive With Measurable Disease | Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (Cohort 1, Cohort 2, Cohort 4 and Cohorts 1 and 2 Combined) | 6.0 Percentage of Participants |
| Cohort 2: PD-L1 Negative With Measurable Disease | Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (Cohort 1, Cohort 2, Cohort 4 and Cohorts 1 and 2 Combined) | 3.0 Percentage of Participants |
| Cohort 4: RECIST 1.1-measureable Disease | Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (Cohort 1, Cohort 2, Cohort 4 and Cohorts 1 and 2 Combined) | 12.3 Percentage of Participants |
| Cohorts 1 and 2 Combined | Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (Cohort 1, Cohort 2, Cohort 4 and Cohorts 1 and 2 Combined) | 5.0 Percentage of Participants |
Secondary
Disease Control Rate (DCR) (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, Cohorts 4 and 5 Combined)
Percentage of participants who had CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions)or stable disease (SD; Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease) for at least 6 months, by central imaging vendor where progressive disease (PD) in bone-only tumors were determined by radionuclide bone scan using Prostate Cancer Working Group (PCWG3) criteria and PD for all other tumors was determined using RECIST 1.1. Per protocol, analysis for this outcome measure was conducted in Cohorts 1 and 2 combined, Cohorts 1,2, and 3 combined, Cohorts 4 and 5 combined well as in Cohorts 1 to 5 separately for the first course of treatment.
Time frame: Up to ~52 months
Population: Analysis population was the ASaT which consisted of all allocated participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: PD-L1 Positive With Measurable Disease | Disease Control Rate (DCR) (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, Cohorts 4 and 5 Combined) | 10.5 Percentage of Participants |
| Cohort 2: PD-L1 Negative With Measurable Disease | Disease Control Rate (DCR) (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, Cohorts 4 and 5 Combined) | 4.5 Percentage of Participants |
| Cohort 4: RECIST 1.1-measureable Disease | Disease Control Rate (DCR) (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, Cohorts 4 and 5 Combined) | 24.1 Percentage of Participants |
| Cohorts 1 and 2 Combined | Disease Control Rate (DCR) (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, Cohorts 4 and 5 Combined) | 29.6 Percentage of Participants |
| Cohort 5: Bone Metastases Only or Bone-predominant Disease | Disease Control Rate (DCR) (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, Cohorts 4 and 5 Combined) | 31.1 Percentage of Participants |
| Cohorts 1 and 2 Combined | Disease Control Rate (DCR) (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, Cohorts 4 and 5 Combined) | 8.5 Percentage of Participants |
| Cohorts 1, 2, and 3 Combined | Disease Control Rate (DCR) (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, Cohorts 4 and 5 Combined) | 12.0 Percentage of Participants |
| Cohorts 4 and 5 Combined | Disease Control Rate (DCR) (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, Cohorts 4 and 5 Combined) | 30.2 Percentage of Participants |
Secondary
DOR- Per RECIST 1.1 (Cohort 1, Cohort 2, Cohort 4 and Cohorts 1 and 2 Combined)
DOR was defined as the time from first documented evidence of complete response (CR; disappearance of all target lesions) or partial response (PR; ≥30% decrease in the sum of diameters of target lesions) ) until progressive disease (PD) assessed by central imaging where PD was determined by radionuclide bone scan using RECIST 1.1 and PD for all other tumors was determined using RECIST 1.1 or death due to any cause, whichever occurred first. Per protocol, analysis for this outcome measure was conducted in Cohorts 1, 2 and 4 separately, well as in Cohorts 1 and 2 combined for the first course of treatment.
Time frame: Up to ~52 months
Population: The analysis was based on all responders with measurable disease at baseline in the ASaT population which consisted of all allocated participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: PD-L1 Positive With Measurable Disease | DOR- Per RECIST 1.1 (Cohort 1, Cohort 2, Cohort 4 and Cohorts 1 and 2 Combined) | NA Months |
| Cohort 2: PD-L1 Negative With Measurable Disease | DOR- Per RECIST 1.1 (Cohort 1, Cohort 2, Cohort 4 and Cohorts 1 and 2 Combined) | NA Months |
| Cohort 4: RECIST 1.1-measureable Disease | DOR- Per RECIST 1.1 (Cohort 1, Cohort 2, Cohort 4 and Cohorts 1 and 2 Combined) | NA Months |
| Cohorts 1 and 2 Combined | DOR- Per RECIST 1.1 (Cohort 1, Cohort 2, Cohort 4 and Cohorts 1 and 2 Combined) | NA Months |
Secondary
Duration of PSA Response (Cohorts 4 and 5 by Cohort and Combined)
Duration of PSA response was defined as the time from PSA response, when the PSA value first declined by at least 50% of the baseline (must have been confirmed by a second value), to the date of PSA progression at which there was an increase of 25% or more from the nadir PSA, provided the absolute increase from the nadir PSA was at least 2 ng/mL. Per protocol, analysis for this outcome measure was conducted in Cohorts 4 and 5 separately and combined for the first course of treatment.
Time frame: Up to ~52 months
Population: Analysis population was the ASaT which consisted of all allocated participants who received at least 1 dose of study treatment and had a confirmed PSA response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: PD-L1 Positive With Measurable Disease | Duration of PSA Response (Cohorts 4 and 5 by Cohort and Combined) | 8.3 Months |
| Cohort 2: PD-L1 Negative With Measurable Disease | Duration of PSA Response (Cohorts 4 and 5 by Cohort and Combined) | 18.0 Months |
| Cohort 4: RECIST 1.1-measureable Disease | Duration of PSA Response (Cohorts 4 and 5 by Cohort and Combined) | 18.0 Months |
Secondary
Duration of Response (DOR) Per PCWG3-modified RECIST 1.1 (Cohort 1, Cohort 2, Cohort 4 and Cohorts 1 and 2 Combined)
DOR was defined as the time from first documented evidence of complete response (CR; disappearance of all target lesions) or partial response (PR; ≥30% decrease in the sum of diameters of target lesions) until progressive disease (PD) assessed by central imaging where PD was determined by radionuclide bone scan using Prostate Cancer Working Group (PCWG3)-modified RECIST 1.1 criteria and PD for all other tumors was determined using RECIST 1.1 or death due to any cause, whichever occurred first. Per protocol, analysis for this outcome measure was conducted in Cohorts 1, 2 and 4 separately, well as in Cohorts 1 and 2 combined for the first course of treatment.
Time frame: Up to ~52 months
Population: The analysis was based on all responders with measurable disease at baseline in the ASaT population which consisted of all allocated participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: PD-L1 Positive With Measurable Disease | Duration of Response (DOR) Per PCWG3-modified RECIST 1.1 (Cohort 1, Cohort 2, Cohort 4 and Cohorts 1 and 2 Combined) | NA Months |
| Cohort 2: PD-L1 Negative With Measurable Disease | Duration of Response (DOR) Per PCWG3-modified RECIST 1.1 (Cohort 1, Cohort 2, Cohort 4 and Cohorts 1 and 2 Combined) | NA Months |
| Cohort 4: RECIST 1.1-measureable Disease | Duration of Response (DOR) Per PCWG3-modified RECIST 1.1 (Cohort 1, Cohort 2, Cohort 4 and Cohorts 1 and 2 Combined) | NA Months |
| Cohorts 1 and 2 Combined | Duration of Response (DOR) Per PCWG3-modified RECIST 1.1 (Cohort 1, Cohort 2, Cohort 4 and Cohorts 1 and 2 Combined) | NA Months |
Secondary
Overall Survival (OS) (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, Cohorts 4 and 5 Combined)
OS was defined as the time from first day of study treatment to the time of death. Participants without documented death were censored at the date of the last follow up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. Per protocol, analysis for this outcome measure was conducted in Cohorts 1 and 2 combined, Cohorts 1,2, and 3 combined, Cohorts 4 and 5 combined well as in Cohorts 1 to 5 separately for the first course of treatment.
Time frame: Up to ~52 months
Population: Analysis population was the ASaT which consisted of all allocated participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: PD-L1 Positive With Measurable Disease | Overall Survival (OS) (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, Cohorts 4 and 5 Combined) | 9.5 Months |
| Cohort 2: PD-L1 Negative With Measurable Disease | Overall Survival (OS) (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, Cohorts 4 and 5 Combined) | 7.9 Months |
| Cohort 4: RECIST 1.1-measureable Disease | Overall Survival (OS) (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, Cohorts 4 and 5 Combined) | 14.1 Months |
| Cohorts 1 and 2 Combined | Overall Survival (OS) (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, Cohorts 4 and 5 Combined) | 17.6 Months |
| Cohort 5: Bone Metastases Only or Bone-predominant Disease | Overall Survival (OS) (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, Cohorts 4 and 5 Combined) | 20.8 Months |
| Cohorts 1 and 2 Combined | Overall Survival (OS) (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, Cohorts 4 and 5 Combined) | 8.1 Months |
| Cohorts 1, 2, and 3 Combined | Overall Survival (OS) (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, Cohorts 4 and 5 Combined) | 9.6 Months |
| Cohorts 4 and 5 Combined | Overall Survival (OS) (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, Cohorts 4 and 5 Combined) | 18.9 Months |
Secondary
Percentage of Participants Who Discontinued Study Treatment Due to an AE
An AE was defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The percentage of participants who discontinued study treatment during the first course of treatment due to an AE was reported.
Time frame: Up to ~52 months
Population: Analysis population was the ASaT which consisted of all allocated participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: PD-L1 Positive With Measurable Disease | Percentage of Participants Who Discontinued Study Treatment Due to an AE | 10.5 Percentage of Participants |
| Cohort 2: PD-L1 Negative With Measurable Disease | Percentage of Participants Who Discontinued Study Treatment Due to an AE | 3.0 Percentage of Participants |
| Cohort 4: RECIST 1.1-measureable Disease | Percentage of Participants Who Discontinued Study Treatment Due to an AE | 12.1 Percentage of Participants |
| Cohorts 1 and 2 Combined | Percentage of Participants Who Discontinued Study Treatment Due to an AE | 18.5 Percentage of Participants |
| Cohort 5: Bone Metastases Only or Bone-predominant Disease | Percentage of Participants Who Discontinued Study Treatment Due to an AE | 20.0 Percentage of Participants |
Secondary
Percentage of Participants Who Experienced an Adverse Event (AE)
An AE was defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The percentage of participants that experienced at least one AE for the first course of treatment was reported.
Time frame: Up to ~52 months
Population: Analysis population was the ASaT which consisted of all allocated participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: PD-L1 Positive With Measurable Disease | Percentage of Participants Who Experienced an Adverse Event (AE) | 99.2 Percentage of Participants |
| Cohort 2: PD-L1 Negative With Measurable Disease | Percentage of Participants Who Experienced an Adverse Event (AE) | 97.0 Percentage of Participants |
| Cohort 4: RECIST 1.1-measureable Disease | Percentage of Participants Who Experienced an Adverse Event (AE) | 100.0 Percentage of Participants |
| Cohorts 1 and 2 Combined | Percentage of Participants Who Experienced an Adverse Event (AE) | 98.8 Percentage of Participants |
| Cohort 5: Bone Metastases Only or Bone-predominant Disease | Percentage of Participants Who Experienced an Adverse Event (AE) | 97.8 Percentage of Participants |
Secondary
Prostate-specific Antigen (PSA) Response Rate (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined and Cohorts 4 and 5 Combined)
Percentage of participants who had PSA response defined as at least 50% decline from baseline measured twice at least 3 weeks apart. Per protocol, analysis for this outcome measure was conducted in Cohorts 1 and 2 combined, Cohorts 1, 2, and 3 combined, Cohorts 4 and 5 combined well as in Cohorts 1 to 5 for the first course of treatment.
Time frame: Up to ~52 months
Population: Analysis population was the ASaT which consisted of all allocated participants who received at least one dose of study treatment and had a PSA measurement at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: PD-L1 Positive With Measurable Disease | Prostate-specific Antigen (PSA) Response Rate (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined and Cohorts 4 and 5 Combined) | 6.5 Percentage of Participants |
| Cohort 2: PD-L1 Negative With Measurable Disease | Prostate-specific Antigen (PSA) Response Rate (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined and Cohorts 4 and 5 Combined) | 8.2 Percentage of Participants |
| Cohort 4: RECIST 1.1-measureable Disease | Prostate-specific Antigen (PSA) Response Rate (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined and Cohorts 4 and 5 Combined) | 1.7 Percentage of Participants |
| Cohorts 1 and 2 Combined | Prostate-specific Antigen (PSA) Response Rate (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined and Cohorts 4 and 5 Combined) | 16.3 Percentage of Participants |
| Cohort 5: Bone Metastases Only or Bone-predominant Disease | Prostate-specific Antigen (PSA) Response Rate (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined and Cohorts 4 and 5 Combined) | 8.9 Percentage of Participants |
| Cohorts 1 and 2 Combined | Prostate-specific Antigen (PSA) Response Rate (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined and Cohorts 4 and 5 Combined) | 7.0 Percentage of Participants |
| Cohorts 1, 2, and 3 Combined | Prostate-specific Antigen (PSA) Response Rate (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined and Cohorts 4 and 5 Combined) | 5.8 Percentage of Participants |
| Cohorts 4 and 5 Combined | Prostate-specific Antigen (PSA) Response Rate (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined and Cohorts 4 and 5 Combined) | 13.6 Percentage of Participants |
Secondary
Radiographic Progression-free Survival (rPFS) - Per PCWG3-modified RECIST 1.1 (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, and Cohorts 4 and 5 Combined)
rPFS was defined as the time from first day of study treatment to the documented disease progression by central imaging vendor where PD in bone-only tumors was determined by radionuclide bone scan using PCWG3 criteria and PD for all other tumors were determined using RECIST 1.1 or death due to any cause, whichever occurs first. Per protocol, analysis for this outcome measure was conducted in Cohorts 1 and 2 combined, Cohorts 1,2, and 3 combined, Cohorts 4 and 5 combined well as in Cohorts 1 to 5 separately for the first course of treatment.
Time frame: Up to ~52 months
Population: Analysis population was the ASaT which consisted of all allocated participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: PD-L1 Positive With Measurable Disease | Radiographic Progression-free Survival (rPFS) - Per PCWG3-modified RECIST 1.1 (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, and Cohorts 4 and 5 Combined) | 2.1 Months |
| Cohort 2: PD-L1 Negative With Measurable Disease | Radiographic Progression-free Survival (rPFS) - Per PCWG3-modified RECIST 1.1 (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, and Cohorts 4 and 5 Combined) | 2.1 Months |
| Cohort 4: RECIST 1.1-measureable Disease | Radiographic Progression-free Survival (rPFS) - Per PCWG3-modified RECIST 1.1 (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, and Cohorts 4 and 5 Combined) | 3.7 Months |
| Cohorts 1 and 2 Combined | Radiographic Progression-free Survival (rPFS) - Per PCWG3-modified RECIST 1.1 (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, and Cohorts 4 and 5 Combined) | 4.2 Months |
| Cohort 5: Bone Metastases Only or Bone-predominant Disease | Radiographic Progression-free Survival (rPFS) - Per PCWG3-modified RECIST 1.1 (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, and Cohorts 4 and 5 Combined) | 4.4 Months |
| Cohorts 1 and 2 Combined | Radiographic Progression-free Survival (rPFS) - Per PCWG3-modified RECIST 1.1 (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, and Cohorts 4 and 5 Combined) | 2.1 Months |
| Cohorts 1, 2, and 3 Combined | Radiographic Progression-free Survival (rPFS) - Per PCWG3-modified RECIST 1.1 (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, and Cohorts 4 and 5 Combined) | 2.1 Months |
| Cohorts 4 and 5 Combined | Radiographic Progression-free Survival (rPFS) - Per PCWG3-modified RECIST 1.1 (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined, and Cohorts 4 and 5 Combined) | 4.2 Months |
Secondary
Time to First Skeletal-related Event (Cohorts 4 and 5 By Cohort and Combined)
Time to initiation of first skeletal-related event was defined as the time from first day of study treatment to the first skeletal-related event, which was defined as radiation therapy or surgery to bone, pathologic bone fracture, spinal cord compression, or change or antineoplastic therapy to treat bone pain. Per protocol, analysis for this outcome measure was conducted in Cohorts 4 and 5 separately and combined for the first course of treatment.
Time frame: Up to ~52 months
Population: Analysis population was the ASaT which consisted of all allocated participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: PD-L1 Positive With Measurable Disease | Time to First Skeletal-related Event (Cohorts 4 and 5 By Cohort and Combined) | NA Months |
| Cohort 2: PD-L1 Negative With Measurable Disease | Time to First Skeletal-related Event (Cohorts 4 and 5 By Cohort and Combined) | NA Months |
| Cohort 4: RECIST 1.1-measureable Disease | Time to First Skeletal-related Event (Cohorts 4 and 5 By Cohort and Combined) | NA Months |
Secondary
Time to Initiation of Cytotoxic Chemotherapy (Cohorts 4 and 5 by Cohort and Combined)
Time to initiation of cytotoxic chemotherapy was defined as the time from first day of study treatment to the time of initiation of cytotoxic chemotherapy for prostate cancer. The median time was calculated using the Kaplan-Meier method for censored data. Per protocol, analysis for this outcome measure was conducted in Cohorts 4 and 5 separately and combined for the first course of treatment.
Time frame: Up to ~52 months
Population: Analysis population was the ASaT which consisted of all allocated participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: PD-L1 Positive With Measurable Disease | Time to Initiation of Cytotoxic Chemotherapy (Cohorts 4 and 5 by Cohort and Combined) | 11.1 Months |
| Cohort 2: PD-L1 Negative With Measurable Disease | Time to Initiation of Cytotoxic Chemotherapy (Cohorts 4 and 5 by Cohort and Combined) | 11.3 Months |
| Cohort 4: RECIST 1.1-measureable Disease | Time to Initiation of Cytotoxic Chemotherapy (Cohorts 4 and 5 by Cohort and Combined) | 11.1 Months |
Secondary
Time to New-Anticancer Therapy (Cohorts 4 and 5 By Cohort and Combined)
Time to new-anticancer therapy was defined as the time from first day of study treatment to the time of new-anticancer therapy for prostate cancer. The median time was calculated using the Kaplan-Meier method for censored data. Per protocol, analysis for this outcome measure was conducted in Cohorts 4 and 5 separately and combined for the first course of treatment.
Time frame: Up to ~52 months
Population: Analysis population was the ASaT which consisted of all allocated participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: PD-L1 Positive With Measurable Disease | Time to New-Anticancer Therapy (Cohorts 4 and 5 By Cohort and Combined) | 9.5 Months |
| Cohort 2: PD-L1 Negative With Measurable Disease | Time to New-Anticancer Therapy (Cohorts 4 and 5 By Cohort and Combined) | 9.5 Months |
| Cohort 4: RECIST 1.1-measureable Disease | Time to New-Anticancer Therapy (Cohorts 4 and 5 By Cohort and Combined) | 9.5 Months |
Secondary
Time to PSA Progression (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined and Cohorts 4 and 5 Combined)
Time to PSA progression was defined as the time from first day of study treatment to the date of PSA progression. Participants without PSA progression were censored at the last PSA assessment date. PSA progression was defined as the date that an increase of 25% or more and an absolute increase of 2 ng/mL or more from the nadir were documented. For participants who had a decline in PSA during treatment, PSA progression must have been confirmed by a second value 3 or more weeks later increased with respect to the nadir PSA. Per protocol, analysis for this outcome measure was conducted in Cohorts 1 and 2 combined, Cohorts 1,2, and 3 combined, Cohorts 4 and 5 combined well as in Cohorts 1 to 5 separately for the first course of treatment.
Time frame: Up to ~52 months
Population: Analysis population was the ASaT which consisted of all allocated participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: PD-L1 Positive With Measurable Disease | Time to PSA Progression (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined and Cohorts 4 and 5 Combined) | 5.1 Months |
| Cohort 2: PD-L1 Negative With Measurable Disease | Time to PSA Progression (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined and Cohorts 4 and 5 Combined) | 6.2 Months |
| Cohort 4: RECIST 1.1-measureable Disease | Time to PSA Progression (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined and Cohorts 4 and 5 Combined) | 4.2 Months |
| Cohorts 1 and 2 Combined | Time to PSA Progression (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined and Cohorts 4 and 5 Combined) | 5.6 Months |
| Cohort 5: Bone Metastases Only or Bone-predominant Disease | Time to PSA Progression (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined and Cohorts 4 and 5 Combined) | 4.2 Months |
| Cohorts 1 and 2 Combined | Time to PSA Progression (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined and Cohorts 4 and 5 Combined) | 6.2 Months |
| Cohorts 1, 2, and 3 Combined | Time to PSA Progression (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined and Cohorts 4 and 5 Combined) | 4.4 Months |
| Cohorts 4 and 5 Combined | Time to PSA Progression (By Each Cohort, Cohorts 1 and 2 Combined, Cohorts 1, 2, and 3 Combined and Cohorts 4 and 5 Combined) | 4.4 Months |