BMS-986408 + Immunotherapy for Cancer

No longer recruiting at 36 trial locations

Overseen By BMS Study Connect Contact Center http://www.bmsstudyconnect.com

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Bristol-Myers Squibb

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Autoimmune disease, Untreated CNS metastases, 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 tests a new drug, BMS-986408, to evaluate its safety when used alone or with other treatments like nivolumab and ipilimumab, which are types of immunotherapy. Researchers aim to find the most effective dose that patients can tolerate. The trial targets individuals with advanced or hard-to-treat solid cancers that have progressed after previous treatments. Participants with melanoma should have a record of their cancer's genetic mutations. This trial offers a new treatment option if standard therapies have failed. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, giving participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial requires that you stop taking corticosteroids (a type of medication that reduces inflammation) within 14 days and other immunosuppressive medications (drugs that lower the body's immune response) within 30 days before starting the study treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research is investigating the safety of BMS-986408 when used alone and in combination with other drugs like nivolumab and ipilimumab. These studies aim to determine the safest dose and understand the drug's mechanism in the body.

In terms of safety, past patients have shown that BMS-986408, whether used alone or with other drugs, is generally well-tolerated. While some side effects may occur, they are usually manageable. For instance, combining BMS-986408 with nivolumab and ipilimumab can enhance the immune system's response to cancer, and previous studies have examined the safety of this combination.

Nivolumab and ipilimumab are already approved for treating certain cancers, providing some reassurance about their safety. However, researchers continue to study BMS-986408 to understand its safety and mechanism when used with these drugs.

Overall, the trials aim to identify the optimal dose that is both safe and effective, particularly when BMS-986408 is combined with other treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BMS-986408 because it represents a fresh approach to cancer treatment. Unlike traditional options like chemotherapy or radiation that target a broad range of cells, BMS-986408 is designed to work by enhancing the body's immune response specifically against cancer cells. It's often paired with existing immunotherapy drugs, nivolumab and ipilimumab, which are known to block proteins that prevent the immune system from attacking cancer. This combination could potentially offer a more targeted and effective treatment, with fewer side effects compared to traditional therapies. Additionally, the inclusion of combinations with chemotherapy or rabeprazole may provide new ways to enhance its efficacy or manage side effects, making these trials particularly promising.

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

Research has shown that BMS-986408 might aid in treating cancer by enhancing the effectiveness of CAR T-cell therapy, enabling the body to combat cancer cells more efficiently. In this trial, some participants will receive BMS-986408 with nivolumab, a treatment that has extended survival in individuals with non-small cell lung cancer. Additionally, other participants will receive a combination of BMS-986408, nivolumab, and ipilimumab, which has demonstrated strong and lasting effects in treating advanced cancers, such as lung cancer. Researchers aim to determine whether combining BMS-986408 with these treatments can further improve cancer treatment outcomes. ^{4 5 6 7 8}

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 adults with advanced solid tumors that can't be surgically removed or have spread, and who haven't responded to or can't receive standard treatments. Melanoma patients must know their BRAF and NRAS mutation status. People taking steroids or other immune-suppressing drugs recently, those with certain gastrointestinal conditions, or untreated brain metastases cannot join.

Inclusion Criteria

My melanoma has been tested for BRAF and NRAS mutations.

I've tried or can't take standard treatments for my condition.

My cancer is advanced, cannot be surgically removed, and can be measured for treatment response.

Exclusion Criteria

I haven't taken steroids or immunosuppressants in the last 30 days.

I have had recent stomach or intestine problems or surgery that could affect how I absorb medication.

I have brain metastases that have not been treated.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BMS-986408 as monotherapy or in combination with nivolumab, nivolumab and ipilimumab, or chemotherapy to establish the maximum tolerated dose (MTD) and determine the Recommended Phase 2 Dose (RP2D)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BMS-986408
• Ipilimumab
• Nivolumab

Trial Overview

The study is testing the safety of a new drug called BMS-986408 alone and in combination with Nivolumab, as well as together with both Nivolumab and Ipilimumab. It aims to find the highest dose patients can take without serious side effects (MTD) and the best dose for future studies (RP2D).

How Is the Trial Designed?

Group I: Part 3: BMS-986408 in combination with nivolumab and chemotherapy Experimental Treatment 3 Interventions

Group II: Part 3: BMS-986408 in combination with nivolumab Experimental Treatment 2 Interventions

Group III: Part 2: BMS-986408 in combination with rabeprazole Experimental Treatment 2 Interventions

Group IV: Part 2: BMS-986408 in combination with nivolumab and ipilimumab Experimental Treatment 3 Interventions

Group V: Part 2: BMS-986408 in combination with nivolumab and chemotherapy Experimental Treatment 3 Interventions

Group VI: Part 2: BMS-986408 in combination with nivolumab Experimental Treatment 2 Interventions

Group VII: Part 1: BMS-986408 Monotherapy Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Bristol-Myers Squibb

Lead Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

Ipilimumab is an anti-CTLA-4 monoclonal antibody being developed for treating various cancers, including malignant melanoma and prostate cancer, and is currently in phase III trials for these indications.

The drug is also undergoing phase II trials for lymphoma and non-small cell lung cancer, indicating its potential broad application in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab. [2021]

Nivolumab (OPDIVO) received accelerated FDA approval for treating unresectable or metastatic melanoma based on a 31.7% objective response rate in a study of 120 patients, showing promising efficacy after prior treatments.

The treatment demonstrated durable responses, with 87% of responding patients maintaining their response for at least 6 months, although it carries risks of immune-mediated adverse reactions that were monitored in a safety assessment of 268 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. FDA Approval Summary: Nivolumab for Treatment of Unresectable or Metastatic Melanoma Following Progression on Ipilimumab. Hazarika, M., Chuk, MK., Theoret, MR., et al.[2023]

The phase I trial of MEDI5752, a bispecific antibody that targets both PD-1 and CTLA4, shows that the drug is well tolerated by patients.

Preliminary results indicate that MEDI5752 is active in treating various tumor types, with durable responses observed, suggesting potential effectiveness in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MEDI5752 Suppresses Two Immune Checkpoints. [2022]

Nivolumab significantly improved overall survival and progression-free survival in patients with unresectable or metastatic melanoma compared to dacarbazine, with hazard ratios of 0.42 and 0.43 respectively, based on a trial involving 418 patients.

The most common side effects of nivolumab included fatigue, diarrhea, and rash, but it was still considered to have a favorable benefit-risk profile compared to dacarbazine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval of Nivolumab for the First-Line Treatment of Patients with BRAFV600 Wild-Type Unresectable or Metastatic Melanoma. Beaver, JA., Theoret, MR., Mushti, S., et al.[2018]

Nivolumab plus ipilimumab showed durable and long-term efficacy in treating advanced non-small cell lung cancer (NSCLC) compared to chemotherapy, regardless of tumor PD-L1 expression levels.

These findings are based on updated results from part 1 of the phase 3 CheckMate 227 trial, indicating that this combination therapy could be a more effective frontline treatment option for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab/Ipilimumab Combo Yields Durable Efficacy in Advanced NSCLC. Kahl, KL.[2021]

Nivolumab (Opdivo) combined with ipilimumab (Yervoy) has been approved by the FDA as a first-line treatment for adults with unresectable malignant pleural mesothelioma, based on promising results from the CHECKMATE 743 trial.

The approval was supported by an interim analysis comparing the combination therapy to standard chemotherapy, indicating that this new treatment option may offer better outcomes for patients with this challenging cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approves Nivolumab Plus Ipilimumab for Previously Untreated Unresectable Malignant Pleural Mesothelioma. Wright, K.[2021]

Nivolumab, an immune checkpoint inhibitor, significantly improved overall survival and progression-free survival compared to docetaxel in patients with advanced squamous non-small cell lung cancer (NSCLC) in the CheckMate 017 trial.

Nivolumab was better tolerated than docetaxel, with manageable adverse effects, making it a promising treatment option for patients who have already undergone chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: a review in advanced squamous non-small cell lung cancer. Keating, GM.[2022]

Nivolumab (Opdivo) monotherapy led to complete regression of local recurrence and multiple lung metastases in a patient with recurrent skin melanoma and a positive BRAF mutation, demonstrating its efficacy as a treatment option.

After 5 courses of nivolumab, the patient experienced significant improvement in her condition, achieving an ECOG performance status of 0, indicating a return to an active lifestyle without pain, and normal serum LDH levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[EVALUATION OF THE EFFICASY OF THE DRUG OPDIVO (NIVOLUMAB) IN A PATIENT DIAGNOSED WITH UNRESECTABLE SKIN MELANOMA, POSITIVE BRAF MUTATION AND DISEASE DISSEMINATION (CASE REPORT)]. Samsonia, M., Kandelaki, M., Gibradze, O., et al.[2021]

In a study analyzing 2,088 individual case safety reports (ICSRs) related to immune checkpoint inhibitors (ICIs) in Italy, 801 reports documented serious immune-related adverse drug reactions (irADRs), primarily affecting male patients with gastrointestinal and skin toxicities.

Among the ICIs, nivolumab and pembrolizumab were most frequently associated with irADRs, with significant risks identified for pembrolizumab and ipilimumab, highlighting the need for oncologists to recognize and manage these serious side effects effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Inhibitors and Immune-Related Adverse Drug Reactions: Data From Italian Pharmacovigilance Database. Ruggiero, R., Fraenza, F., Scavone, C., et al.[2022]

The phase I/IIa study of BMS-986178, an OX40 agonist, showed a manageable safety profile with low rates of severe treatment-related adverse events (5% for monotherapy and up to 15% for combination therapy), indicating it is safe for use in patients with advanced solid tumors.

Despite the safety, the study did not find significant efficacy for BMS-986178 alone or in combination with nivolumab and/or ipilimumab, with no objective responses observed in monotherapy and low response rates (0% to 13%) in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OX40 Agonist BMS-986178 Alone or in Combination With Nivolumab and/or Ipilimumab in Patients With Advanced Solid Tumors. Gutierrez, M., Moreno, V., Heinhuis, KM., et al.[2022]

Nivolumab combined with a multi-peptide vaccine was well tolerated in 33 patients with resected stage IIIC and IV melanoma, with no maximum tolerated dose reached and manageable side effects like fatigue and rash.

The treatment showed promising results with a median relapse-free survival of 47.1 months, indicating potential effectiveness in preventing cancer recurrence in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, correlative markers, and clinical results of adjuvant nivolumab in combination with vaccine in resected high-risk metastatic melanoma. Gibney, GT., Kudchadkar, RR., DeConti, RC., et al.[2022]

Citations

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pmc.ncbi.nlm.nih.gov/articles/PMC12402804/

Discovery of BMS-986408, a First-In-Class Dual DGKα and ...

BMS-986408 also markedly improved CD19-targeted CAR T-cell therapy efficacy by overcoming hypofunctionality, insufficient expansion, and lack of costimulatory ...

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clinicaltrials.eu/inn/bms-986408/

BMS-986408: A Promising Drug for Advanced Solid Tumors

This phase 1/2 study aims to assess the safety and effectiveness of BMS-986408 when used alone or in combination with other cancer treatments. The trial ...

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aacrjournals.org/cancerimmunolres/article-pdf/doi/10.1158/2326-6066.CIR-25-0156/3621437/cir-25-0156.pdf

Discovery of BMS-986408, a First-In-Class Dual DGKα and ...

data were then subtracted from the BMS-986408 data to give the log fold change enrichment for ... cells to improve treatment outcomes in solid cancers. Immunother ...

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withpower.com/trial/phase-2-solid-tumors-advanced-solid-tumors-5-2022-86501

BMS-986408 + Immunotherapy for Cancer

Nivolumab plus ipilimumab showed durable and long-term efficacy in treating advanced non-small cell lung cancer (NSCLC) compared to chemotherapy, regardless of ...

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clinicaltrials.gov/study/NCT05407675

NCT05407675 | A Study to Evaluate the Safety and ...

The primary purpose of this study is to characterize the safety profile of BMS-986408 as monotherapy and in combination with nivolumab or nivolumab and ...

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bmsstudyconnect.com/se/en/clinical-trials/NCT05407675.html

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The primary purpose of this study is to characterize the safety profile of BMS-986408 as monotherapy and in combination with nivolumab or ...

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Trial ID CA099-003 | NCT05407675 - BMS Clinical Trials

The primary purpose of this study is to characterize the safety profile of BMS-986408 as monotherapy and in combination with nivolumab or nivolumab and ...