gridegalutamide (BMS-986365) / BMS - LARVOL DELTA

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

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

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 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

Study to Evaluate Safety, Drug Levels, Food and Relative Bioavailability of BMS-986365 in Healthy Adult Male Participants (clinicaltrials.gov) - P1 | N=82 | Active, not recruiting | Sponsor: Celgene | Recruiting ➔ Active, not recruiting

Enrollment closed

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 | Not yet recruiting | Sponsor: Celgene

New P3 trial • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

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 | Recruiting | Sponsor: Celgene | Trial completion date: Sep 2024 ➔ Feb 2025 | Trial primary completion date: Sep 2024 ➔ Feb 2025

Trial completion date • Trial primary completion date

Comparing and Contrasting BMS-986365 and JMKX002992 and other AR degraders for prostate cancer (DAVAGU 2024) - No abstract available.

Clinical

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 | Recruiting ➔ Active, not recruiting

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

BMS-986365 (CC-94676), a Dual Androgen Receptor Ligand-Directed Degrader and Antagonist, for the Treatment of Advanced Prostate Cancer (PCF 2024) - No abstract available

Metastases • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

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

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

Phase I/II trial of BMS-986365 in mCRPC resistant to ARPIs (YouTube) - "Andrew Armstrong, MD...discusses updated findings from the Phase I/II CC-94676-PCA-001 trial (NCT04428788) of BMS-986365, a novel dual-action AR degrader and antagonist, in patients with metastatic castration-resistant prostate cancer (mCRPC) resistant to androgen receptor pathway inhibitors (ARPI). The treatment was well tolerated with no grade 4 adverse events, and demonstrated prolonged radiographic progression-free survival, particularly in patients with no prior chemotherapy."

Interview • Video

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 | Recruiting | Sponsor: Celgene | Not yet recruiting ➔ Recruiting

Enrollment open

PROTAC'ing the androgen receptor and other emerging therapeutics in prostate cancer. (PubMed, Expert Rev Anticancer Ther) - "PROTACs, DAARIs, and anitens represent novel and promising AR-targeting therapeutics that may become an important part of prostate cancer treatment in the future. Elucidating mechanisms of resistance, including ability of these agents to target full length AR, may yield further insights into maximal therapeutic efficacy aimed at silencing AR signaling."

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

Study to Evaluate Safety, Drug Levels, Food and Relative Bioavailability of BMS-986365 in Healthy Adult Male Participants (clinicaltrials.gov) - P1 | N=82 | Recruiting | Sponsor: Celgene | Not yet recruiting ➔ Recruiting

Enrollment open

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 | Not yet recruiting | Sponsor: Celgene

New P1 trial

Study to Evaluate Safety, Drug Levels, Food and Relative Bioavailability of BMS-986365 in Healthy Adult Male Participants (clinicaltrials.gov) - P1 | N=82 | Not yet recruiting | Sponsor: Celgene

New P1 trial

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 • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • AR

Thrilled to share the first report of our new AR degrader BMS-986365 in this @ThePCCTC phase 1-2 trial! Active drug, durable responses seen! See Dr Rathkopf’s poster here! @DukeGUCancer @DukeCancer @bmsnews

Bristol Myers Squibb Data at ASCO GU 2024 Showcase Transformative Research in the Treatment of Genitourinary Cancers (Businesswire) - "Key data being presented by Bristol Myers Squibb at ASCO GU 2024 include: Four-year follow-up data from the Phase 3 CheckMate -9ER trial evaluating Opdivo in combination with Exelixis’ CABOMETYX (cabozantinib). These data demonstrate meaningful, long-term efficacy benefits seen with the combination therapy over sunitinib and reinforce it as a standard of care for previously untreated advanced RCC. First presentation of clinical outcomes from the company’s targeted protein degradation platform in solid tumors with Phase 1 data from BMS-986365 (CC-94676), an oral drug selectively targeting AR."

P1 data • P3 data • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor