E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Castration-resistant Prostate Cancer |
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E.1.1.1 | Medical condition in easily understood language |
Cancer that has spread (metastasized) beyond the prostate gland and for which hormone therapy is no longer effective in stopping or slowing the disease. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036909 |
E.1.2 | Term | Prostate cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1. To assess the safety, tolerability, and DLTs of docetaxel in combination with BMS-986218 or in combination with BMS-986218 plus nivolumab in participants with mCRPC (Part 1). 2. To compare the rPFS in mCRPC participants treated with docetaxel and either docetaxel in combination with BMS-986218 or docetaxel in combination with BMS-986218 and nivolumab (Part 2). |
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E.2.2 | Secondary objectives of the trial |
1. To assess the antitumor activity of the combination of docetaxel with BMS-986218 or BMS-986218 and nivolumab in mCRPC participants, based on ORR, TTR, and DOR (Part 2). 2. To assess PSA response rate (PSA-RR) and time to PSA progression (TTP-PSA; limited to participants with measurable PSA [defined as ≥ 2 ng/ml] at baseline) (Part 2). 3. To assess overall survival (OS) (Part 2). 4. To characterize safety of BMS-986218 in combination with docetaxel, and with nivolumab and docetaxel in Part 2. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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).
Other protocol-defined inclusion criteria apply. |
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E.4 | Principal 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 exclusion criteria apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Incidence of AEs, SAEs, AEs meeting protocol-defined DLT criteria, TRAEs, AEs leading to discontinuation, and deaths. 2. rPFS for randomized participants is the time between randomization date and the first date of documented radiographic progression, or death due to any cause, whichever occurs first. The radiographic progression will be assessed by blinded independent central review (BICR) per PCWG3. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Any time in Part 1. 2. First date of documented radiographic progression, or death due to any cause, whichever occurs first. |
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E.5.2 | Secondary end point(s) |
1. a) 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. b) 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. c) 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 PCWG.
2. a) 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. b) TTP-PSA is the time between randomization date to the date of PSA progression per PCWG3 in randomized participants.
3. OS for all randomized participants is the time between randomization date and the date of death from any cause.
4. Overall safety and tolerability will be measured by the incidence of AEs, TRAEs, SAEs, AEs leading to discontinuation, and deaths. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. a) Date of objectively documented radiographic progression, or last tumor measurement, whichever occurs first. b) Date of the first documented CR or PR per PCWG3. c) Date of first documented radiographic progression per PCWG3 (as determined by BICR), or death due to any cause.
2. a) Date when 50% or greater decrease in PSA occurs compared to baseline. b) Date of PSA progression per PCWG3.
3. End of study.
4. End of study. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Optional Crossover Treatment (Arm 2d) for Participants Randomized to Part 2 Arm 2a. |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Canada |
United States |
France |
Netherlands |
Spain |
Greece |
Italy |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of trial is defined as the last participant last visit or scheduled procedure shown in the Schedule of Activities for the last participant. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 30 |