BMS-986218 + Nivolumab for Cancer

Recruiting at 101 trial locations

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

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Bristol-Myers Squibb

Must not be taking: Cytotoxic agents

Disqualifiers: Primary CNS malignancies, CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 83 months

376 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that at least 4 weeks must pass since your last dose of certain anti-cancer therapies before starting the study treatment.

What data supports the effectiveness of the drug combination BMS-986218 and Nivolumab for cancer?

Nivolumab, one of the drugs in the combination, has shown significant improvement in survival rates and response rates in patients with advanced squamous non-small cell lung cancer, as demonstrated in the CheckMate 017 trial. ^{1 2 3 4 5}

Is the combination of BMS-986218 and Nivolumab safe for humans?

Nivolumab, also known as Opdivo, has been studied in various cancers and is generally considered safe, with manageable side effects, including immune-related reactions. It has been used in combination with other drugs like Ipilimumab (Yervoy) and has shown a tolerable safety profile in patients with advanced cancers. ^{1 2 4 6 7}

What makes the drug combination of BMS-986218 and Nivolumab unique for cancer treatment?

The combination of BMS-986218 and Nivolumab is unique because BMS-986218 is an OX40 agonist that can enhance the immune system's response to cancer, while Nivolumab is a PD-1 inhibitor that helps the immune system recognize and attack cancer cells. This dual approach aims to boost the body's natural defenses against tumors more effectively than using either drug alone. ^{1 2 3 4 8}

What is the purpose of this trial?

This trial is testing whether a new drug, BMS-986218, alone or with Nivolumab, is safe for patients with advanced solid tumors. These drugs help the immune system fight cancer. Nivolumab is a treatment that has been used for various cancers, including melanoma, lung cancer, and renal cell carcinoma.

Research Team

Bristol Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This trial is for adults with advanced solid tumors who've tried at least two standard treatments without success. It's open to those with specific cancers like melanoma, lung cancer, and colorectal cancer that haven't spread to the brain. Participants should be fairly active and healthy otherwise (with a performance status of 0 or 1).

Inclusion Criteria

My cancer has worsened or not responded well to at least 2 standard treatments.

I have advanced skin cancer and have tried standard treatments, including immunotherapy.

I have NSCLC and have completed standard treatments, including immunotherapy.

Exclusion Criteria

I do not have brain cancer or cancer that has only spread to my brain.

It's been over 4 weeks since my last cancer treatment.

I have had previous cancer treatments like chemotherapy or immunotherapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BMS-986218 alone or in combination with Nivolumab to assess safety and tolerability in advanced solid tumors

Up to approximately 83 months

Multiple visits as per cycle schedule

Follow-up

Participants are monitored for safety and effectiveness after treatment

100 days following last dose

Treatment Details

Interventions

• BMS-986218
• Ipilimumab
• Nivolumab

Trial Overview Researchers are testing BMS-986218 alone and alongside Nivolumab to see if they're safe for treating advanced solid tumors. The study will explore different combinations of these drugs in participants who have already undergone other treatments.

Participant Groups

Group I: Part 2D: Expansion Combination Therapy (BMS-986218 + Nivolumab) Experimental Treatment 2 Interventions

Group II: Part 2C: Expansion Combination Therapy (BMS-986218 + Nivolumab) Experimental Treatment 2 Interventions

Group III: Part 2B: Monotherapy (BMS-986218) Experimental Treatment 1 Intervention

Group IV: Part 2A: Monotherapy (BMS-986218 OR Ipilimumab) Experimental Treatment 2 Interventions

Group V: Part 1B: Combination Therapy (BMS-986218 + Nivolumab) Experimental Treatment 2 Interventions

Group VI: Part 1A: Monotherapy (BMS-986218) 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, 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, an immune checkpoint inhibitor, significantly improves overall survival and progression-free survival in patients with advanced stage squamous cell non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CHECKMATE 017 study.

The safety and tolerability of nivolumab are favorable, and interestingly, the expression of the PD-L1 ligand does not predict treatment outcomes, suggesting that other factors may influence the effectiveness of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab in the treatment of metastatic squamous non-small cell lung cancer: a review of the evidence. Lim, JS., Soo, RA.[2018]

Nivolumab, an anti-PD-1 antibody, was administered to a 63-year-old female patient with metastatic melanoma after renal transplantation, highlighting the potential for anti-tumor activity in high-risk patients, despite the challenges of concurrent immunosuppression.

The patient experienced acute renal allograft rejection and renal failure shortly after starting nivolumab, indicating significant risks associated with this treatment in transplant recipients, but she later showed a positive clinical response after re-challenging with nivolumab while on hemodialysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. Ong, M., Ibrahim, AM., Bourassa-Blanchette, S., 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]

In a phase I/II trial involving 38 patients with newly diagnosed metastatic melanoma, the combination of bempegaldesleukin and nivolumab resulted in responses in 20 patients, indicating potential efficacy.

The treatment combination was associated with relatively few side effects, suggesting a favorable safety profile for this therapeutic approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bempegaldesleukin Ups Melanoma Responses. [2020]

The combination of ibrutinib and nivolumab demonstrated an acceptable safety profile in 141 patients with relapsed or refractory B-cell malignancies, with only one dose-limiting toxicity reported, indicating that this treatment approach is generally safe for patients.

Preliminary results showed promising efficacy, with overall response rates of 61% in high-risk chronic lymphocytic leukaemia, 33% in follicular lymphoma, and 36% in diffuse large B-cell lymphoma, suggesting that this combination therapy could be effective for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and activity of ibrutinib in combination with nivolumab in patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukaemia: a phase 1/2a study. Younes, A., Brody, J., Carpio, C., 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]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

Nivolumab in the treatment of metastatic squamous non-small cell lung cancer: a review of the evidence. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. [2023]

4. 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]

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

Bempegaldesleukin Ups Melanoma Responses. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Safety and activity of ibrutinib in combination with nivolumab in patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukaemia: a phase 1/2a study. [2021]

7. 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]

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

Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. [2022]