BMS-986365 Shows Promise in Phase 3 Trial for Advanced Prostate Cancer Resistant to Standard Therapies
Key Insights
BMS-986365, a dual androgen receptor degrader and antagonist, demonstrated well-tolerated safety profile and promising anti-tumor activity in heavily pretreated metastatic castration-resistant prostate cancer patients.
The novel oral drug showed potential to overcome resistance to current androgen receptor pathway inhibitors regardless of AR genomic status in first-in-human studies.
A Phase 3 trial (rechARge) is now recruiting at 230 sites across 24 countries, comparing BMS-986365 to investigator's choice of standard therapies.
Bristol Myers SquibbView company profile's investigational drug BMS-986365Search drug has advanced to Phase 3 testing for metastatic castration-resistant prostate cancerSearch disease (mCRPC), marking a significant milestone for this novel androgen receptorSearch term-targeting therapy that has shown promise in overcoming treatment resistance.
Phase 3 Trial Launches Globally
The rechARge trial (CA071-1000) is recruiting patients at 230 sites across 24 countries and territories in North America, Europe, Latin America, and East Asia. In Part 1 of the dose selection phase, patients are randomized 1:1:1 to receive either BMS-986365Search drug at 400 or 300 mg twice daily every 28 days, or investigator's choice comprising androgen receptorSearch term pathway inhibitors (enzalutamideSearch drug 160 mg daily or abirateroneSearch drug 1000 mg daily plus prednisoneSearch drug) every 28 days, or docetaxelSearch drug 75 mg/m² plus prednisone every 21 days for up to 10 cycles.
Secondary endpoints include safety, overall response rate, confirmed PSA response rate (PSA30 and PSA50), and patient reported outcomes, providing comprehensive assessment of the drug's therapeutic potential.
Encouraging Phase 1 Results Drive Development
Updated results from the first-in-human, multicenter study presented at the American Urology Association meeting showed promising outcomes. Data from Part B dose expansion included 68 patients treated at 400, 600, or 900 mg twice daily (20 patients each dose level).
"Treatment with BMS-986365Search drug was well tolerated, with a manageable safety profile and promising anti-tumor activity," according to the study authors. "These data show the potential of BMS-986365 to overcome resistance to current ARPI (Androgen ReceptorSearch term Pathway Inhibitors) in a large segment of patients regardless of ARSearch term genomic status."
Dr. Manish Patel from Florida Cancer Specialists & Research InstituteSearch company, who presented the abstract, noted that "these insights equate to good news as we continue our work to improve survival rates for patients with advanced prostate cancerSearch disease."
Novel Dual Mechanism of Action
BMS-986365Search drug represents a new class of therapeutics known as androgen receptorSearch term ligand-directed degraders (ARSearch term LDD) with dual mechanism of action. The drug both degrades and inhibits the androgen receptor, potentially offering advantages over current standard-of-care treatments.
Preclinical studies demonstrated that BMS-986365Search drug is approximately 100-fold more potent than enzalutamideSearch drug at inhibiting androgen-stimulated transcription of ARSearch term target genes, and 10 to 120-fold more potent than enzalutamide at inhibiting AR-dependent proliferation of multiple prostate cancerSearch disease cell lines in vitro.
Addressing Treatment Resistance
The majority of mCRPC remains androgen receptorSearch term-dependent even when resistant to current ARSearch term pathway inhibitors such as enzalutamideSearch drug and abirateroneSearch drug. BMS-986365Search drug showed particular promise in heavily pretreated patients post-ARPI, with encouraging durability especially in patients with no prior chemotherapy.
The drug demonstrated activity regardless of ARSearch term genomic status, suggesting broad applicability across different patient populations. Treatment was well tolerated with no grade 4 adverse events reported, and patients experienced prolonged radiographic progression-free survival, particularly those without prior chemotherapy exposure.
Preclinical Validation Supports Clinical Development
Supporting preclinical data from CC2000199Search drug, a close analog of BMS-986365Search drug, showed significant tumor volume reductions in validated models of advanced castration-resistant prostate cancerSearch disease and therapy-resistant patient-derived xenografts, including those with acquired resistance to enzalutamideSearch drug. These models suggest that ARSearch term degraders may be superior to standard-of-care AR antagonists in disease-relevant animal models and enzalutamide-resistant mCRPC that remain dependent on androgen receptorSearch term signaling.