Phase II Trial of BMS-986365 Switch in Metastatic Castration-Sensitive Prostate Cancer with Suboptimal PSA Response after ADT and ARPI

The primary objective is to evaluate the efficacy of switching from an ARPI to BMS-986365 in men with metastatic castrate-sensitive prostate cancer and a suboptimal PSA response after 7 months of combined ADT plus ARPI treatment. The primary endpoint is the PSA response rate, which is clinically relevant as an indicator of biochemical disease control. Secondary objectives are to assess additional surrogate efficacy parameters, including confirmed PSA response rates of 30%, 50%, and 90%, time to PSA response, and duration of PSA response. Further objectives include characterization of safety and tolerability, exploration of overall survival, evaluation of ECOG performance status and patient-reported outcomes, and analysis of androgen receptor alterations in tumor tissue and peripheral blood, as well as ctDNA dynamics and their association with clinical efficacy.

The sponsor did not provide the total number of participants. The study population consisted of adult males aged 18 years and older with documented metastatic castrate sensitive prostate cancer. Participants were selected based on ongoing treatment with androgen deprivation therapy and one of the specified androgen receptor pathway inhibitors, a detectable PSA level 7 months after initiation of anti-hormonal treatment, and a minimum prior ARPI treatment duration of 4 months. The population was required to have ECOG performance status 0 or 1 and adequate blood count, liver, and renal function. Participants could be asymptomatic or symptomatic from metastatic prostate cancer, provided that pain status and pain medication use were stable for at least 4 weeks before registration. No lifestyle considerations were provided.

This is a phase 2, open-label, single-arm trial in men with metastatic castrate-sensitive prostate cancer and suboptimal PSA response after 7 months of androgen deprivation therapy plus androgen receptor pathway inhibition. The investigational treatment is oral BMS-986365 600 mg capsules. The main objective is to assess efficacy by confirmed PSA 50% response rate. Study participation begins with a screening visit to verify eligibility criteria, including disease status, PSA level, prior treatment exposure, performance status, symptoms, and adequate blood, liver, and renal function. Eligible participants then enter treatment and undergo follow-up visits during the study to assess PSA response, safety, laboratory values, ECG findings, adverse events, and other protocol-defined outcomes. An end-of-study visit is performed at treatment completion or early discontinuation to document final assessments. The overall trial duration is planned from 25 May 2026 to 25 May 2029, and the expected individual duration of participation is not specified. Early termination from the study may occur if eligibility requirements are no longer met, if treatment is discontinued, or if adverse events, dose modifications, interruptions, or other protocol-defined reasons lead to stopping study participation.

BMS-986365 was administered as an oral capsule at a dose of 600 mg. The treatment was given by oral use according to the trial regimen. The study evaluated an ARPI to BMS-986365 switch in participants with suboptimal PSA response after 7 months of combined ADT plus ARPI treatment for mCSPC. No additional non-experimental treatment, placebo, or comparator product was specified in the source data. Information on dosing adjustments, administration schedule details beyond the stated dose and route, and compliance monitoring was not provided.

Efficacy will be assessed in participants with metastatic castrate sensitive prostate cancer using confirmed PSA 50% response rate as the primary endpoint. Secondary efficacy assessments will include confirmed PSA 30% and 90% response rates, confirmed absolute PSA response rates defined by PSA thresholds, time to PSA progression, time to mCRPC, rPFS, time to pain progression, time to symptomatic skeletal related event, time to initiation of the first subsequent systemic therapy, overall survival, and changes from baseline in NCCN FACT FPSI-17 total and subscale scores, EQ-5D-5L, and BPI-SF. Efficacy-related biomarker assessments will also include analysis of AR copy number, splice variants and mutations at baseline, ctDNA detection rate at baseline, and changes in ctDNA from baseline during treatment.