BMS-986365 for Healthy Subjects

No longer recruiting at 1 trial location

Overseen By First line of the email MUST contain the NCT# and Site #.

Age: 18 - 65

Sex: Male

Trial Phase: Phase 1

Sponsor: Celgene

Disqualifiers: Heart failure, Ischemic heart diseases, Arrhythmias, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the new drug BMS-986365 (also known as CC-94676 or Gridegalutamide) moves through and is processed by the body. Researchers aim to understand how the drug is absorbed, broken down, and eliminated to ensure its safety and effectiveness. The trial includes different parts to test the drug in various ways. Healthy men without major health issues, such as heart disease or significant stomach problems, are ideal candidates for this study. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

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

The trial protocol does not specify if you need to stop taking your current medications. However, since the trial is for healthy subjects, it's likely that participants should not be on any significant medications. Please consult with the trial coordinators for more details.

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 past studies. Patients taking BMS-986365 experienced side effects that were generally mild and manageable. These studies included individuals who had already tried many other treatments. Even for this challenging group, the treatment remained safe. Although this trial is in the early stages, earlier findings suggest that BMS-986365 is likely safe for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

BMS-986365 is unique because it offers a new approach that might differentiate it from existing treatments. While most treatments for various conditions often rely on established mechanisms of action, BMS-986365 may introduce a novel mechanism that targets the problem differently, potentially leading to improved outcomes. Researchers are particularly excited about this treatment because it could provide an alternative option for patients who do not respond well to current therapies. Additionally, any new delivery method or active ingredient involved could offer benefits like enhanced effectiveness or fewer side effects, making it a promising candidate in its field.

What evidence suggests that this trial's treatments could be effective?

Research suggests that BMS-986365, studied in this trial, could be a promising treatment for certain types of cancer. Studies have shown that patients generally tolerated this drug well, and it had a manageable safety profile. The drug targets and breaks down proteins that help cancer grow. Early results indicated that it might slow or stop the progression of specific cancers. While more research is needed to confirm its effectiveness, these initial findings encourage further study. Participants in this trial will join one of the various treatment arms to further evaluate the safety and efficacy of BMS-986365. ^{1 2 3 4 6}

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 male participants. Specific eligibility criteria are not provided, but typically such studies require individuals without significant health issues who can comply with the study requirements.

Inclusion Criteria

Participants will require a left ventricular ejection fraction of > 50% at screening

Healthy male participants as determined by no clinically significant deviations from normal in medical history, physical examination, 12-lead ECGs, or clinical laboratory determinations, as determined by the investigator

My BMI is between 18.0 and 32.0.

Exclusion Criteria

I do not have any serious illnesses right now.

History of allergy to BMS-986365 or related compounds

I have a history of serious heart conditions or a long QT interval.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part A

Assessment of pharmacokinetics and absolute bioavailability of BMS-986365

Up to 15 days

Multiple visits (in-person)

Part B

Investigation of PK, metabolite profile, routes and extent of elimination, and mass balance of BMS-986365

Up to 60 days

Multiple visits (in-person)

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 and related compounds to understand how they're processed in the body (pharmacokinetics), their availability when taken orally (bioavailability), and how they're eliminated from the body.

How Is the Trial Designed?

Group I: Part B - Arm 2 Experimental Treatment 1 Intervention

Group II: Part B - Arm 1 Experimental Treatment 1 Intervention

Group III: Part A Experimental Treatment 2 Interventions

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-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]

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]

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]

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]

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]

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]

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]

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-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]

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]

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]

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]

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]

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 ... Conclusions: BMS-986365 was well tolerated, with a manageable safety profile, and demonstrated activity in heavily pretreated patients with mCRPC with ...