gridegalutamide (BMS-986365) / BMS - LARVOL DELTA

A Study of BMS986365 in Combination With Degarelix in People With Prostate Cancer (clinicaltrials.gov) - P2 | N=7 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | N=30 ➔ 7 | Recruiting ➔ Active, not recruiting

Enrollment change • Enrollment closed • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

rechARge: A Study to Compare the Efficacy and Safety of BMS-986365 Versus the Investigator's Choice of Therapy in Participants With Metastatic Castration-resistant Prostate Cancer (clinicaltrials.gov) - P3 | N=960 | Active, not recruiting | Sponsor: Celgene | Recruiting ➔ Active, not recruiting

Enrollment closed • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

A Phase 3 Trial of the Androgen Receptor Ligand-directed Degrader BMS-986365 Versus Investigator's Choice in Patients with Metastatic Castration-resistant Prostate Cancer (CA071-1000 – rechARge) (AUA 2026) - P3 | "In Part 1 (dose selection), patients will be randomized 1:1:1 to receive either BMS-986365 400 or 300 mg BID Q28D, or investigator's choice of ARPI of either enzalutamide (160 mg QD) or abiraterone (1000 mg QD + prednisone/prednisolone 5 mg BID) Q28D or docetaxel 75 mg/m2 Q21D (up to a maximum of 10 cycles) + prednisone/prednisolone 5 mg BID. Other secondary endpoints include safety, overall response rate, confirmed PSA response rate (PSA30 and PSA50), and patient-reported outcomes.The study targets recruiting ∼275 sites (including 54 sites in the US) in 26 countries/territories across North America, Europe, South America, and East Asia. (Not all sites or countries are open for Part 1, some will be open later at the start of Part 2.)"

Clinical • First-in-human • Metastases • P3 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • AR

Safety and clinical activity of BMS-986365 (CC-94676), a dual androgen receptor ligand-directed degrader and antagonist, in heavily pretreated patients with metastatic castration-resistant prostate cancer. (PubMed, Ann Oncol) - P1 | "BMS-986365 was well tolerated, with a manageable safety profile, and demonstrated activity in heavily pretreated patients with potentially higher benefit in chemotherapy-naïve patients. These data show BMS-986365's potential to overcome resistance to current ARPIs, regardless of AR LBD mutation status."

Clinical • Journal • Metastases • Cardiovascular • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • Targeted Protein Degradation

Clinical activity of BMS-986365 (CC-94676), a dual androgen receptor (AR) ligand-directed degrader and antagonist, in heavily pretreated patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) (ESMO 2024) - P1 | "Background: The majority of mCRPC remains AR-dependent even if resistant to AR pathway inhibitors (ARPI) such as enzalutamide (ENZ) and abiraterone (ABI). BMS-986365 demonstrated activity in heavily pretreated pts post-ARPI, especially encouraging durability in pts with no prior CT, and was well tolerated, with a manageable safety profile. These data show potential of BMS-986365 to overcome resistance to current ARPI in a large segment of pts regardless of AR genomic status. Table: 1597MO Data by dose BID, twice a day; PSA, prostate-specific antigen; PSAXX, ≥ XX% decline in PSA (locally assessed, best % change, either confirmed or unconfirmed, from baseline); NE, not estimable; rPFS, radiographic progression-free survival."

Clinical • Metastases • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • AR

BMS-986365 (CC-94676), a dual androgen receptor ligand-directed degrader and antagonist, for heavily pretreated patients with metastatic castration-resistant prostate cancer: results from additional exploratory analyses (AUA 2025) - P1 | "BMS-986365 demonstrated activity in heavily pretreated pts post-ARPI and had encouraging durability in pts with no prior CT. Treatment with BMS-986365 was well tolerated, with a manageable safety profile. These data show the potential of BMS-986365 to overcome resistance to current ARPI in a large segment of pts regardless of AR genomic status."

Clinical • Metastases • Cardiovascular • Castration-Resistant Prostate Cancer • Fatigue • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR

A phase 2 study of androgen deprivation therapy and the androgen receptor ligand–directed degrader (BMS-986365) prior to radical prostatectomy in patients with high-risk localized prostate cancer. (ASCO 2026) - P2, P3 | "An ongoing phase 3 study is evaluating ADT plus apalutamide for 6 months prior to RP in pts with high-risk or locally advanced PC; co-primary endpoints are pathologic complete response (pCR) and metastasis-free survival (NCT03767244)...Pts will receive degarelix SC once monthly (first dose 240mg, maintenance dose 80mg) and BMS-986365 at a dose of 300mg PO twice daily (liquid-filled capsule formulation) for 6 months; RP will occur 2 weeks after the last dose of BMS-986365...As part of exploratory analyses, cfDNA, pre-/post-treatment (prostatectomy) tissue, and pre-/post-treatment multiparametric MRI will be collected. The study opened to accrual in January 2026."

Clinical • P2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Study to Evaluate the Effect of Itraconazole and Rifampin on the Drug Levels of AR-LDD (BMS-986365) in Healthy Adult Male Participants (clinicaltrials.gov) - P1 | N=22 | Terminated | Sponsor: Celgene | N=42 ➔ 22 | Recruiting ➔ Terminated; Business objectives have changed

Enrollment change • Trial termination

Discovery of Potential First-in-Class Dual Ligand-Directed Degrader and Antagonist of the Androgen Receptor: BMS-986365. (PubMed, J Med Chem) - "This dual mechanism results in the robust inhibition of AR-driven pathways and prostate cancer cell growth. The development of BMS-986365 highlights the potential of targeted protein degradation strategies to overcome resistance and improve therapeutic outcomes in prostate cancer."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Targeted Protein Degradation • AR

Can PROTACs truly become oral drugs? (PubMed, Drug Discov Today) - "Although a growing number of PROTACs are administered orally in clinical studies, and several have demonstrated measurable systemic exposure and pharmacodynamic activity (such as ARV-110, ARV-471, and BMS-986365), the ability to reliably design PROTACs with predictable oral bioavailability remains limited. We argue that the field will benefit greatly from adopting an 'oral-first' conformation-centric approach, discovering new E3 ligases and ligands, earlier predictive modeling, and strategic formulation technologies. Progressing alternative modalities in parallel might further expand opportunities for developing orally viable protein-elimination therapies."

Journal • Review • Targeted Protein Degradation • CRBN

Phase 2 trial of ARPI to AR-degrader (BMS-986365) switch for suboptimal PSA-response in mCSPC (eARly-SWITCH). (clinicaltrialsregister.eu) - P1/2 | N=42 | Not yet recruiting | Sponsor: UroTrials GmbH, AIO-Studien gGmbH

New P1/2 trial • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Discovery of BMS-986365, a ligand-directed androgen receptor degrader (AR LDD) with a dual mechanism-of-action and best-in-class potential, for the treatment of advanced prostate cancer (AACR 2024) - "The drug is ~100-fold more potent than enzalutamide (ENZ) at inhibiting androgen-stimulated transcription of AR target genes, and 10 to 120-fold more potent than ENZ at inhibiting AR-dependent proliferation of multiple prostate cancer cell lines in vitro. Collectively our preclinical data suggest that the AR degrader BMS-986365 is superior to standard-of-care AR antagonists, such as ENZ, in both preclinical and disease-relevant animal models, and support its clinical development for treatment of prostate cancer. BMS-986365 has advanced into clinical studies where it has demonstrated encouraging clinical activity in patients with mCRPC."

Metastases • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR

CC2000199, a potent and selective androgen receptor ligand-directed degrader (AR LDD) with a dual mechanism of action, exhibits anti-tumor activity in multiple enzalutamide-resistant preclinical models for metastatic castration-resistant prostate cancer (AACR 2025) - "CC2000199 (also called CC-199) is a heterobifunctional ligand‑directed degrader (LDD) that enables CRL4CRBN E3 ligase-dependent ubiquitination and degradation of AR and a close analog of BMS-986365. Indeed, significant tumor volume reductions were achieved by CC-199 in validated models of advanced CRPC and therapy resistant patient-derived xenografts, including those with acquired resistance to ENZ. Collectively, our preclinical data suggest that the AR degrader CC-199 is superior to standard-of-care AR antagonists, such as ENZ, in disease-relevant animal models and ENZ-resistant mCRPC that remain dependent on AR."

Metastases • Preclinical • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • FKBP5

A Study of BMS986365 in Combination With Degarelix in People With Prostate Cancer (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center

New P2 trial • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Study to Evaluate the Effect of Itraconazole and Rifampin on the Drug Levels of AR-LDD (BMS-986365) in Healthy Adult Male Participants (clinicaltrials.gov) - P1 | N=42 | Recruiting | Sponsor: Celgene | Not yet recruiting ➔ Recruiting

Enrollment open

CC-94676-PCA-001: Study to Evaluate the Safety and Tolerability of CC-94676 in Participants With Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=131 | Completed | Sponsor: Celgene | Active, not recruiting ➔ Completed | N=250 ➔ 131 | Trial completion date: Dec 2026 ➔ Oct 2025

Enrollment change • Trial completion • Trial completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

A Study to Evaluate the Effect of Itraconazole and Rifampin on the Drug Levels of AR-LDD (BMS-986365) in Healthy Adult Male Participants (clinicaltrials.gov) - P1 | N=42 | Not yet recruiting | Sponsor: Celgene

New P1 trial

Discovery of BMS-986365, a first-in-class dual androgen receptor ligand-directed degrader (AR LDD) and antagonist, for the treatment of advanced prostate cancer. (PubMed, Clin Cancer Res) - "The preclinical observations, coupled with clinical data, strongly support the potential for BMS-986365 to overcome ARPI-resistant disease regardless of AR mutational status. These findings establish BMS-986365 as a first-in-class, dual AR degrader and competitive antagonist, likely to emerge as an important tool in the armamentarium to treat PC."

Journal • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CRBN

CC-94676-PCA-001: Study to Evaluate the Safety and Tolerability of CC-94676 in Participants With Metastatic Castration-Resistant Prostate Cancer (clinicaltrials.gov) - P1 | N=250 | Active, not recruiting | Sponsor: Celgene | Trial primary completion date: Jun 2025 ➔ Oct 2025

Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

A phase 3 trial of the androgen receptor ligand-directed degrader, BMS-986365, versus investigator's choice in patients with metastatic castration-resistant prostate cancer (CA071-1000 - rechARge). (ASCO 2025) - P3 | "In Part 1 (dose selection), patients will be randomized 1:1:1 to receive either BMS-986365 400 or 300 mg BID Q28D, or investigator's choice comprising ARPI (enzalutamide [160 mg QD] or abiraterone [1000 mg QD + prednisone] Q28D); or docetaxel 75 mg/m2 + prednisone Q21D up to a maximum of 10 cycles. Other secondary endpoints include safety, overall response rate, confirmed PSA response rate (PSA30 and PSA50), and patient reported outcomes. The study is recruiting at 230 sites in 24 countries/territories across North America, Europe, Latin America, and East Asia."

Clinical • Metastases • P3 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Pain • Prostate Cancer • Solid Tumor • AR

rechARge: a randomized phase III trial of the androgen receptor ligand-directed degrader, BMS-986365, vs investigator's choice in patients with mCRPC. (PubMed, Future Oncol) - P3 | "Here, we present the study design of rechARge, a phase III, randomized, multicenter, adaptive, two-part, open-label trial evaluating BMS-986365 versus investigator's choice of therapy comprising either docetaxel or a switch to an alternative ARPI (abiraterone or enzalutamide) in patients with mCRPC whose disease has progressed after treatment with one prior ARPI. The primary study objective is to compare the efficacy and safety of BMS-986365 versus investigator's choice of therapy. Approximately 960 patients will be enrolled.Clinical trial registration: www.clinicaltrials.gov identifier is NCT06764485."

Journal • P3 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Targeted Protein Degradation

Manish R. Patel, MD is Oral Presenter of Abstract Analyzing Effectiveness of First-In-Human Study of Cutting-Edge Treatment For Advanced Prostate Cancer at AUA meeting (PRNewswire) - P1 | N=250 | NCT04428788 | Sponsor: Celgene | "The abstract details updated results from the first-in-human, multicenter study of BMS-986365, a new type of orally-administered drug that degrades and inhibits the Androgen Receptor. Data reported are from the Part B dose expansion at 400, 600 or 900 mg BID (n=20 each) among 68 patients. Treatment with BMS-986365 was well tolerated, with a manageable safety profile and promising anti-tumor activity. These data show the potential of BMS-986365 to overcome resistance to current ARPI (Androgen Receptor Pathway Inhibitors) in a large segment of patients regardless of AR genomic status."

P1 data • Castration-Resistant Prostate Cancer

A Study to Evaluate the Drug Levels, Metabolism and Excretion, and Absolute Bioavailability of BMS-986365 in Healthy Male Participants (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: Celgene | Recruiting ➔ Completed

Trial completion

rechARge: A Study to Compare the Efficacy and Safety of BMS-986365 Versus the Investigator's Choice of Therapy in Participants With Metastatic Castration-resistant Prostate Cancer (clinicaltrials.gov) - P3 | N=960 | Recruiting | Sponsor: Celgene | Not yet recruiting ➔ Recruiting

Enrollment open • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Study to Evaluate Safety, Drug Levels, Food and Relative Bioavailability of BMS-986365 in Healthy Adult Male Participants (clinicaltrials.gov) - P1 | N=102 | Completed | Sponsor: Celgene | Active, not recruiting ➔ Completed

Trial completion