Prostatic Neoplasms, Castration-Resistant
Conditions
Keywords
BMS-986218, BMS-936558, Docetaxel, Metastatic, MDX1106, Nivolumab, ONO-4538, TAXOTERE
Brief summary
The purpose of this study is to assess the safety, efficacy, tolerability, and toxicity of docetaxel alone, in combination with BMS-986218, or in combination with nivolumab plus BMS-986218 in men who have metastatic castration-resistant prostate cancer (mCRPC) that progressed after novel antiandrogen therapy and have not received chemotherapy for mCRPC.
Interventions
BIOLOGICALBMS-986218
Specified dose on specified days
DRUGDocetaxel
Specified dose on specified days
BIOLOGICALNivolumab
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologic confirmation of carcinoma of the prostate without small cell features * Documented prostate cancer progression by Prostate Cancer Working Group 3 (PCWG3) criteria while castrate * Evidence of metastatic disease documented by either bone lesions on radionuclide bone scan and/or soft tissue lesions on computed tomography (CT)/magnetic resonance imaging (MRI) * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 * Ongoing androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone (GnRH) agonist/antagonist or bilateral orchiectomy (i.e., surgical or medical castration) confirmed by testosterone level ≤ 1.73 nmol/L (50 ng/dL) at the screening visit * Chemotherapy-naive for metastatic castration-resistant prostate cancer (mCRPC) and have received at least one novel antiandrogen therapy (NAT)
Exclusion criteria
* Concurrent malignancy (present during screening) requiring treatment or history of prior malignancy active within 2 years prior to treatment assignment in Part 1 or randomization in Part 2 * Untreated central nervous system (CNS) metastases * Leptomeningeal metastases * Active, known or suspected autoimmune disease Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Died | From first dose to 100 days follow up to last dose (Approximately 22 months) | Number of participant deaths |
| Number of Participants With Treatment Related Adverse Events | From first dose to 100 days follow up to last dose (Approximately 22 months) | Adverse events will presented using National Cancer Institute Common Terminology Criteria for Adverse Events version 5 (NCI CTCAE v5). |
| Number of Participants With Treatment Related Serious Adverse Events | From first dose to 100 days follow up to last dose (Approximately 22 months) | Adverse events will presented using National Cancer Institute Common Terminology Criteria for Adverse Events version 5 (NCI CTCAE v5). |
| Number of Participants With Dose Limiting Toxicities | From first dose to 100 days follow up to last dose (Approximately 22 months) | DLTs will be defined as: Any treatment-related AEs for which a participant permanently discontinues a study treatment (other than daily prednisone) and that occurs during the first 2 cycles of treatment. Any death not clearly due to the underlying disease or extraneous causes and that occurs during the first 2 cycles of treatment Greater than or equal to Grade 2 pneumonitis lasting greater than 5 days despite appropriate medical therapy and that occurs during the first 2 cycles of treatment Any neutropenic fever as well as Grade 4 neutropenia or thrombocytopenia for \> 7 days that occurs during the first 2 cycles of treatment Any treatment-related AE that delays initiation of Cycle 2 or Cycle 3 of treatment by greater than 2 consecutive weeks. |
| Number of Participants With AEs Leading to Discontinuation | From first dose to 100 days follow up to last dose (Approximately 22 months) | Adverse events will presented using National Cancer Institute Common Terminology Criteria for Adverse Events version 5 (NCI CTCAE v5). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prostate Specific Antigen Response Rate (PSA-RR) | From first dose to 100 days follow up to last dose (Approximately 22 months) | PSA-RR is the proportion of randomized participants with a 50% or greater decrease in PSA from baseline to any post-baseline PSA result. A second consecutive value obtained 3 or more weeks later is required to confirm the PSA response. |
| Objective Response Rate | From first dose to 100 days follow up to last dose (Approximately 22 months) | Objective response rate per PCWG3 (ORR-PCWG3) is the proportion of participants who have a confirmed complete or partial best overall response (BOR) per PCWG3 among randomized participants who have measurable disease at baseline. The BOR is defined as the best response designation, as determined by the BICR, recorded between the date of randomization and the date of objectively documented radiographic progression, or last tumor measurement, whichever occurs first. |
| Time to Response | From first dose to 100 days follow up to last dose (Approximately 22 months) | Time to response per PCWG3 (TTR-PCWG3) is the time from randomization date to the date of the first documented CR or PR per PCWG3, as determined by BICR. |
| Duration of Response | From first dose to 100 days follow up to last dose (Approximately 22 months) | Duration of response per PCWG3 (DOR-PCWG3) is the time between the date of first response (CR/PR per PCWG3) to the date of first documented radiographic progression per PCWG3 (as determined by BICR), or death due to any cause. |
| Overall Survival | From first dose to 100 days follow up to last dose (Approximately 22 months) | OS for all randomized participants is the time between randomization date and the date of death from any cause. |
Countries
France, Italy, United States
Participant flow
Pre-assignment details
10 Participants enrolled and Treated. Study terminated early after safety lead in portion (part 1).
Participants by arm
| Arm | Count |
|---|---|
| Treatment 1 BMS-986218 30mg Q3W + Docetaxel 75 mg/m² Q3W | 3 |
| Treatment 2 BMS-986218 50mg Q3W + Docetaxel 75 mg/m² Q3W | 7 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 3 |
| Overall Study | Other Reason | 0 | 1 |
| Overall Study | Participant request to discontinue treatment | 0 | 1 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Progressive Disease | 1 | 1 |
Baseline characteristics
| Characteristic | Treatment 2 | Total | Treatment 1 |
|---|---|---|---|
| Age, Continuous | 65.7 Years STANDARD_DEVIATION 9.14 | 66.5 Years STANDARD_DEVIATION 8.1 | 68.3 Years STANDARD_DEVIATION 6.11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 8 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 9 Participants | 3 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 7 Participants | 10 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 3 | 2 / 7 |
| other Total, other adverse events | 3 / 3 | 7 / 7 |
| serious Total, serious adverse events | 1 / 3 | 6 / 7 |
Outcome results
Primary
Number of Participants Who Died
Number of participant deaths
Time frame: From first dose to 100 days follow up to last dose (Approximately 22 months)
Population: All treated Participants in part 1
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment 1 | Number of Participants Who Died | 2 Participants |
| Treatment 2 | Number of Participants Who Died | 2 Participants |
Primary
Number of Participants With AEs Leading to Discontinuation
Adverse events will presented using National Cancer Institute Common Terminology Criteria for Adverse Events version 5 (NCI CTCAE v5).
Time frame: From first dose to 100 days follow up to last dose (Approximately 22 months)
Population: All treated Participants in part 1
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment 1 | Number of Participants With AEs Leading to Discontinuation | 2 Participants |
| Treatment 2 | Number of Participants With AEs Leading to Discontinuation | 4 Participants |
Primary
Number of Participants With Dose Limiting Toxicities
DLTs will be defined as: Any treatment-related AEs for which a participant permanently discontinues a study treatment (other than daily prednisone) and that occurs during the first 2 cycles of treatment. Any death not clearly due to the underlying disease or extraneous causes and that occurs during the first 2 cycles of treatment Greater than or equal to Grade 2 pneumonitis lasting greater than 5 days despite appropriate medical therapy and that occurs during the first 2 cycles of treatment Any neutropenic fever as well as Grade 4 neutropenia or thrombocytopenia for \> 7 days that occurs during the first 2 cycles of treatment Any treatment-related AE that delays initiation of Cycle 2 or Cycle 3 of treatment by greater than 2 consecutive weeks.
Time frame: From first dose to 100 days follow up to last dose (Approximately 22 months)
Population: All treated Participants in part 1
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment 1 | Number of Participants With Dose Limiting Toxicities | 1 Participants |
| Treatment 2 | Number of Participants With Dose Limiting Toxicities | 0 Participants |
Primary
Number of Participants With Treatment Related Adverse Events
Adverse events will presented using National Cancer Institute Common Terminology Criteria for Adverse Events version 5 (NCI CTCAE v5).
Time frame: From first dose to 100 days follow up to last dose (Approximately 22 months)
Population: All treated Participants in part 1
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment 1 | Number of Participants With Treatment Related Adverse Events | 3 Participants |
| Treatment 2 | Number of Participants With Treatment Related Adverse Events | 7 Participants |
Primary
Number of Participants With Treatment Related Serious Adverse Events
Adverse events will presented using National Cancer Institute Common Terminology Criteria for Adverse Events version 5 (NCI CTCAE v5).
Time frame: From first dose to 100 days follow up to last dose (Approximately 22 months)
Population: All treated Participants in part 1
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment 1 | Number of Participants With Treatment Related Serious Adverse Events | 1 Participants |
| Treatment 2 | Number of Participants With Treatment Related Serious Adverse Events | 4 Participants |
Secondary
Duration of Response
Duration of response per PCWG3 (DOR-PCWG3) is the time between the date of first response (CR/PR per PCWG3) to the date of first documented radiographic progression per PCWG3 (as determined by BICR), or death due to any cause.
Time frame: From first dose to 100 days follow up to last dose (Approximately 22 months)
Population: Study was terminated after safety lead in portion of part 1. Efficacy Data in part 2 was not collected, which includes this endpoint.
Secondary
Objective Response Rate
Objective response rate per PCWG3 (ORR-PCWG3) is the proportion of participants who have a confirmed complete or partial best overall response (BOR) per PCWG3 among randomized participants who have measurable disease at baseline. The BOR is defined as the best response designation, as determined by the BICR, recorded between the date of randomization and the date of objectively documented radiographic progression, or last tumor measurement, whichever occurs first.
Time frame: From first dose to 100 days follow up to last dose (Approximately 22 months)
Population: Study was terminated after safety lead in portion of part 1. Efficacy Data in part 2 was not collected, which includes this endpoint.
Secondary
Overall Survival
OS for all randomized participants is the time between randomization date and the date of death from any cause.
Time frame: From first dose to 100 days follow up to last dose (Approximately 22 months)
Population: Study was terminated after safety lead in portion of part 1. Efficacy Data in part 2 was not collected, which includes this endpoint.
Secondary
Prostate Specific Antigen Response Rate (PSA-RR)
PSA-RR is the proportion of randomized participants with a 50% or greater decrease in PSA from baseline to any post-baseline PSA result. A second consecutive value obtained 3 or more weeks later is required to confirm the PSA response.
Time frame: From first dose to 100 days follow up to last dose (Approximately 22 months)
Population: PSA Evaluable Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment 1 | Prostate Specific Antigen Response Rate (PSA-RR) | Unconfirmed or Confirmed PSA responders | 33.3 Percentage of Participants |
| Treatment 1 | Prostate Specific Antigen Response Rate (PSA-RR) | Confirmed PSA responders | 33.3 Percentage of Participants |
| Treatment 2 | Prostate Specific Antigen Response Rate (PSA-RR) | Unconfirmed or Confirmed PSA responders | 57.1 Percentage of Participants |
| Treatment 2 | Prostate Specific Antigen Response Rate (PSA-RR) | Confirmed PSA responders | 57.1 Percentage of Participants |
Secondary
Time to Response
Time to response per PCWG3 (TTR-PCWG3) is the time from randomization date to the date of the first documented CR or PR per PCWG3, as determined by BICR.
Time frame: From first dose to 100 days follow up to last dose (Approximately 22 months)
Population: Study was terminated after safety lead in portion of part 1. Efficacy Data in part 2 was not collected, which includes this endpoint.