BMS-986365 for Healthy Subjects

No longer recruiting at 1 trial location

Overseen By BMS Study Connect Contact Center www.BMSStudyConnect.com

Age: 18 - 65

Sex: Male

Trial Phase: Phase 1

Sponsor: Celgene

Disqualifiers: Heart disease, Arrhythmias, Allergies, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment, BMS-986365 (also known as CC-94676 or Gridegalutamide), to assess its safety and how the body processes it. The study will evaluate different doses and determine whether eating affects the drug's absorption. It is specifically for healthy men without significant illnesses or heart issues, and participants should have a body mass index (BMI) between 18 and 32. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the unique opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications for this trial?

The protocol does not specify if you need to stop taking your current medications, but since the trial is for healthy subjects, you likely shouldn't be on any significant medications.

Is there any evidence suggesting that BMS-986365 is likely to be safe for humans?

Research has shown that BMS-986365 was well-tolerated in earlier studies. The treatment maintained a manageable safety profile for patients who had previously undergone numerous treatments. This indicates that any side effects were generally easy to handle, particularly with dosage adjustments. Overall, these studies reported that BMS-986365 is safe for humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

BMS-986365 is unique because it offers a new approach compared to existing treatments by potentially targeting mechanisms not addressed by current options. Researchers are excited about BMS-986365 because it may have different dosing regimens and formulations that could improve patient outcomes or convenience. This treatment could provide alternative strategies for managing conditions that current therapies, such as traditional medications or biological agents, might not fully address.

What evidence suggests that BMS-986365 could be effective?

Studies have shown that BMS-986365, an oral drug, is generally safe and well-tolerated. Research indicates it targets androgen receptors, which are involved in conditions like prostate cancer. Early findings suggest it can effectively slow tumor growth. In previous studies with patients who have advanced prostate cancer, BMS-986365 demonstrated promising results in fighting tumors. Although the current trial primarily evaluates different dosages and formulations of BMS-986365 in healthy subjects, these results offer hope for its potential in treating certain cancers. ^{1 3 5 6 7}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

This trial is for healthy adult men who can participate in a study to assess the safety of a new medication. Specific eligibility criteria are not provided, but typically participants must meet certain health standards and have no conflicting medical conditions.

Inclusion Criteria

Healthy adult male participants as determined by no clinically significant deviations from normal in medical history, physical examination, vital signs, ECGs, echocardiogram, or clinical laboratory assessments as determined by the investigator

Body mass index (BMI) of 18.0 to 32.0 kg/m^2, inclusive

Exclusion Criteria

I do not have any serious long-term or sudden illnesses.

I have a history of serious heart conditions.

Other protocol-defined inclusion/exclusion criteria apply

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive single ascending doses of BMS-986365 to evaluate safety, tolerability, and pharmacokinetics

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BMS-986365

Trial Overview The study is testing BMS-986365, possibly a new drug, looking at how safe it is and how the body processes it. It will also compare the effects of taking it with food versus without and its bioavailability compared to Rabeprazole.

How Is the Trial Designed?

Group I: Part 2: Cohort 5 BMS-986365 Dose 11 Fasted Followed by Rabeprazole + Rabeprazole and BMS-986365 Experimental Treatment 2 Interventions

Group II: Part 2: Cohort 4 BMS-986365 Dose 9 Fasted Experimental Treatment 1 Intervention

Group III: Part 2: Cohort 4 BMS-986365 Dose 10 Fed Experimental Treatment 1 Intervention

Group IV: Part 1: Cohort 9 BMS-986365 Dose 8 Experimental Treatment 1 Intervention

Group V: Part 1: Cohort 8 BMS-986365 Dose 7 Experimental Treatment 1 Intervention

Group VI: Part 1: Cohort 7 BMS-986365 Dose 6 Experimental Treatment 1 Intervention

Group VII: Part 1: Cohort 6 BMS-986365 Dose 5 Experimental Treatment 1 Intervention

Group VIII: Part 1: Cohort 3 BMS-986365 Dose 4 Experimental Treatment 1 Intervention

Group IX: Part 1: Cohort 2 BMS-986365 Dose 3 Formulation 2 Experimental Treatment 1 Intervention

Group X: Part 1: Cohort 2 BMS-986365 Dose 2 Formulation 1 Experimental Treatment 1 Intervention

Group XI: Part 1: Cohort 1 BMS-986365 Dose 1 Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Celgene

Lead Sponsor

Trials

649

Recruited

130,000+

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Jay Backstrom

Celgene

Chief Medical Officer since 2016

MD

Mark Alles

Celgene

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Published Research Related to This Trial

BMS-955176 is a second-generation HIV-1 maturation inhibitor that shows potent activity against a wide range of HIV-1 variants, with an effective concentration (EC50) of 3.9 nM against engineered viruses and 21 nM against clinical isolates, indicating its strong potential as a treatment option.

This compound works by inhibiting HIV-1 protease cleavage at a critical site in the virus's replication cycle and has shown no antagonistic interactions with other antiretroviral drugs, suggesting it could be effectively combined with existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification and Characterization of BMS-955176, a Second-Generation HIV-1 Maturation Inhibitor with Improved Potency, Antiviral Spectrum, and Gag Polymorphic Coverage. Nowicka-Sans, B., Protack, T., Lin, Z., et al.[2022]

BMS-275183, a new oral cancer treatment, was found to be generally well tolerated, with a maximum tolerated dose (MTD) established at 200 mg/m2, primarily due to side effects like peripheral neuropathy, fatigue, and neutropenia.

The drug showed promising antitumor activity, with tumor responses observed in 9 out of 38 patients with various cancers, leading to the initiation of a phase II trial specifically for non-small cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial with BMS-275183, a novel oral taxane with promising antitumor activity. Bröker, LE., de Vos, FY., van Groeningen, CJ., et al.[2016]

In a study involving 2117 participants treated with semaglutide 2.4 mg for 68 weeks, gastrointestinal adverse events (AEs) like nausea and diarrhea were more common than in the placebo group, but these AEs were mostly mild and transient, with only 4.3% of participants discontinuing treatment due to them.

Weight loss with semaglutide was significant and similar in participants with and without GI AEs, indicating that the weight loss effects of semaglutide are largely independent of these gastrointestinal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastrointestinal tolerability of once-weekly semaglutide 2.4 mg in adults with overweight or obesity, and the relationship between gastrointestinal adverse events and weight loss. Wharton, S., Calanna, S., Davies, M., et al.[2022]

DTCM-g, a new anti-inflammatory compound, effectively impairs the growth and invasion of glioblastoma (GBM) cells in both pediatric and adult models, showing potential as an adjuvant treatment.

The compound also enhances the effectiveness of radiation therapy, indicating that it could improve treatment outcomes for GBM patients when used in combination with existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DTCM-glutarimide Delays Growth and Radiosensitizes Glioblastoma. Roberto, GM., Paiva, HH., Botelho de Souza, LE., et al.[2019]

The bombesin/GRP antagonists RC-3940-II and RC-3940-Et significantly reduced the growth of U-118MG human malignant glioma tumors in nude mice by 52.5% and 72.6%, respectively, over 6 weeks of treatment.

Both antagonists effectively induced apoptosis in tumor cells, as evidenced by a 70% reduction in the Bcl-2:Bax ratio and a significant decrease in VEGF and PKC-alpha levels, suggesting their potential as effective treatments for glioblastomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antagonists of bombesin/gastrin-releasing peptide decrease the expression of angiogenic and anti-apoptotic factors in human glioblastoma. Kanashiro, CA., Schally, AV., Cai, RZ., et al.[2019]

BMS-986001 was found to be safe and well tolerated in a study involving 64 healthy male subjects, with no serious adverse events reported and only 14.6% experiencing mild adverse effects that were not dose-related.

The pharmacokinetics of BMS-986001 showed a linear dose-exposure relationship, indicating consistent absorption and effectiveness across various doses, regardless of whether it was taken with or without food.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, placebo-controlled single-ascending-dose study to evaluate the safety, tolerability and pharmacokinetics of the HIV nucleoside reverse transcriptase inhibitor, BMS-986001, in healthy subjects. Urata, Y., Paintsil, E., Cheng, YC., et al.[2014]

In a phase II trial involving 31 patients with recurrent glioblastoma multiforme, glufosfamide demonstrated modest toxicity but did not show significant clinical antitumor activity, with no objective responses observed.

Only one patient (3%) remained progression-free at 6 months, indicating that glufosfamide may not be an effective treatment option for this type of brain cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European Organization for Research and Treatment of Cancer (EORTC) open label phase II study on glufosfamide administered as a 60-minute infusion every 3 weeks in recurrent glioblastoma multiforme. van den Bent, MJ., Grisold, W., Frappaz, D., et al.[2022]

MK-5046, a selective agonist for the BRS-3 receptor, was found to be safe and tolerable in a study involving healthy and obese male volunteers, with doses ranging from 10 to 160 mg.

The drug caused transient increases in blood pressure and some mild side effects, such as feelings of warmth and erections, but did not significantly affect hunger or glucose levels, indicating its potential for further exploration in obesity treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of MK-5046, a bombesin receptor subtype-3 (BRS-3) agonist, in healthy patients. Reitman, ML., Dishy, V., Moreau, A., et al.[2021]

BMS-181101, a new antidepressant, was well tolerated in a study involving 12 healthy male volunteers, showing that it can be safely administered with or without food.

When taken with food, BMS-181101 had a 25% reduction in peak concentration (Cmax) and a 1-hour delay in the time to reach peak concentration (tmax), but overall pharmacokinetic profiles, including steady state achievement, were not significantly affected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of effect of food on the steady state pharmacokinetics of BMS-181101, an antidepressant, in healthy subjects. Srinivas, NR., Shyu, WC., Lee, J., et al.[2019]

SAR425899, a dual agonist for GLP-1R and GCR, was well tolerated in clinical trials, with gastrointestinal side effects being less severe in patients with type 2 diabetes compared to healthy volunteers.

The treatment significantly lowered fasting plasma glucose and glycated hemoglobin levels in patients with type 2 diabetes, and also resulted in notable weight loss in both healthy volunteers (up to 5.32 kg) and patients with type 2 diabetes (up to 5.46 kg) compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel dual glucagon-like peptide and glucagon receptor agonist SAR425899: Results of randomized, placebo-controlled first-in-human and first-in-patient trials. Tillner, J., Posch, MG., Wagner, F., et al.[2019]

BMS-275183, an oral paclitaxel analogue, showed a significant decrease in peak drug concentration when taken with food, specifically a 39% reduction with a low-fat meal and a 63% reduction with a high-fat meal, but overall drug exposure remained unchanged.

The study suggests that BMS-275183 can be administered using a flat fixed dose rather than adjusting for body surface area, simplifying dosing while maintaining safety, as it was well tolerated with only a few cases of severe toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of food on the pharmacokinetic behavior of the potent oral taxane BMS-275183. Bröker, LE., Valdivieso, M., Pilat, MJ., et al.[2016]

Cilengitide, a cyclic peptide targeting integrins, shows potential as a treatment for glioblastoma, primarily through antiangiogenic effects, but its impact on glioma cell detachment and viability varies across different cell lines.

Preliminary clinical results suggest that cilengitide may enhance the effectiveness of temozolomide-based therapy in patients with specific genetic markers (MGMT promoter methylation), possibly by improving drug delivery to tumor cells rather than directly affecting cell death or migration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cilengitide modulates attachment and viability of human glioma cells, but not sensitivity to irradiation or temozolomide in vitro. Maurer, GD., Tritschler, I., Adams, B., et al.[2021]

Cilengitide (CGT) showed greater sensitivity in treating glioblastoma multiforme (GBM) compared to temozolomide (TMZ) in patient-derived cell lines, indicating its potential as a more effective treatment option.

The combination of CGT with TMZ enhanced tumor growth inhibition specifically in GBM cell lines with a methylated MGMT promoter, suggesting that this combination could be particularly beneficial for certain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cilengitide response in ultra-low passage glioblastoma cell lines: relation to molecular markers. Mullins, CS., Schubert, J., Schneider, B., et al.[2021]

Citations

1. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)04001-8/fulltext

Safety and clinical activity of BMS-986365 (CC-94676), a ... Results from this first-in-human study show that orally bioavailable BMS-986365 was well tolerated with a manageable safety profile and ...

2. urotoday.com urotoday.com/conference-highlights/aua-2025/aua-2025-prostate-cancer/160006-aua-2025-bms-986365-cc-94676-a-dual-androgen-receptor-ligand-directed-degrader-and-antagonist-for-heavily-pre-treated-patients-with-metastatic-castration-resistant-prostate-cancer-results-from-additional-exploratory-analyses.html

AUA 2025: BMS-986365 (CC-94676), A Dual Androgen ... In this report, Dr. Patel presented data on BMS-986365 in patients with mCRPC, previously published in Annals of Oncology,5 as well as ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06764485

NCT06764485 | A Study to Compare the Efficacy and ... The primary objective of this clinical trial is to assess the radiographic progression free survival (rPFS) of BMS-986365 versus investigator's choice ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0923753424040018

Safety and clinical activity of BMS-986365 (CC-94676), a ... Results from this first-in-human study show that orally bioavailable BMS-986365 was well tolerated with a manageable safety profile and demonstrated antitumor ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12150650/

rechARge: a randomized phase III trial of the androgen ... A phase III, randomized, multicenter, adaptive, two-part, open-label trial evaluating BMS-986365 versus investigator's choice of therapy.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39293515/

Safety and clinical activity of BMS-986365 (CC-94676), a dual ... BMS-986365 was well tolerated, with a manageable safety profile, and demonstrated activity in heavily pretreated patients with mCRPC with potentially higher ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04428788

Study to Evaluate the Safety and Tolerability of CC-94676 ... The purpose of this study is to assess the safety, tolerability and preliminary efficacy of CC-94676 in men with progressive metastatic castration resistant ...