BMS-986408 + Immunotherapy for Cancer

Recruiting at 35 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

101 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called BMS-986408 alone and with two other drugs, nivolumab and ipilimumab, to find the safest dose and understand how it works in the body. It likely targets cancer patients who need new treatment options.

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.

What data supports the effectiveness of the drug BMS-986408 + Immunotherapy for Cancer?

The combination of nivolumab (Opdivo) and ipilimumab (Yervoy) has shown durable and long-term effectiveness in treating advanced non-small cell lung cancer and unresectable malignant pleural mesothelioma, compared to chemotherapy. Additionally, nivolumab alone has been effective in treating advanced squamous non-small cell lung cancer and unresectable or metastatic melanoma, showing significant improvements in survival and response rates. ^{1 2 3 4 5}

What safety information is available for BMS-986408, Ipilimumab, and Nivolumab in cancer treatment?

Nivolumab and Ipilimumab, used in cancer treatment, have been associated with immune-related side effects, such as fatigue, diarrhea, and skin reactions. These treatments have been studied in various cancers, and while they can be effective, they may also cause serious immune-related adverse reactions. It's important to discuss potential risks with your healthcare provider. ^{5 6 7 8 9}

What makes the drug BMS-986408 combined with Ipilimumab and Nivolumab unique for cancer treatment?

This treatment is unique because it combines BMS-986408, a novel drug, with two existing immunotherapies, Ipilimumab and Nivolumab, to potentially enhance the immune system's ability to fight cancer. BMS-986408 is an OX40 agonist, which means it helps activate T-cells (a type of immune cell) to attack cancer cells, offering a new approach compared to standard treatments. ^{6 9 10 11 12}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

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

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

Treatment Details

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).

Participant Groups

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

Findings from Research

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]

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/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 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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

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

2. United States pubmed.ncbi.nlm.nih.gov

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

3. New Zealand pubmed.ncbi.nlm.nih.gov

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

4. Georgia (Republic) 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)]. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

U.S. FDA Approval Summary: Nivolumab for Treatment of Unresectable or Metastatic Melanoma Following Progression on Ipilimumab. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

OX40 Agonist BMS-986178 Alone or in Combination With Nivolumab and/or Ipilimumab in Patients With Advanced Solid Tumors. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

FDA Approval of Nivolumab for the First-Line Treatment of Patients with BRAFV600 Wild-Type Unresectable or Metastatic Melanoma. [2018]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Inhibitors and Immune-Related Adverse Drug Reactions: Data From Italian Pharmacovigilance Database. [2022]

9. England pubmed.ncbi.nlm.nih.gov

How Cancers Escape Immune Destruction and Mechanisms of Action for the New Significantly Active Immune Therapies: Helping Nonimmunologists Decipher Recent Advances. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Safety, correlative markers, and clinical results of adjuvant nivolumab in combination with vaccine in resected high-risk metastatic melanoma. [2022]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Ipilimumab. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

MEDI5752 Suppresses Two Immune Checkpoints. [2022]