BMS-986484 + Nivolumab for Solid Tumors

Recruiting at 22 trial locations

Overseen By Anthony El-Khoueiry, Site 0007

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Bristol-Myers Squibb

Disqualifiers: Interstitial lung disease, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

213 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and tolerability of a new treatment, BMS-986484, both alone and in combination with nivolumab (Opdivo), an immunotherapy drug, for individuals with advanced or metastatic solid tumors. These tumors include non-small cell lung cancer, pancreatic cancer, and stomach cancer. Participants must have a tumor that cannot be surgically removed and is measurable by standard criteria. The trial seeks individuals with good overall health performance and specific types of cancer that have spread or returned after treatment. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

A previous study showed that BMS-986484, used alone or with nivolumab, generally caused mild side effects for most patients. When combined with nivolumab, the side effects remained similar. Nivolumab, already approved for some cancers, has known and usually manageable side effects.

However, when BMS-986484, nivolumab, and chemotherapy were used together, some serious side effects occurred. A small number of patients experienced severe reactions, such as infections. These are known risks associated with chemotherapy drugs.

Overall, these studies suggest that BMS-986484, whether used alone or in combination, has manageable side effects with careful monitoring. Nonetheless, side effects are possible and should be discussed with healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BMS-986484 in combination with Nivolumab for treating solid tumors because this duo offers a fresh approach to cancer therapy. Unlike traditional chemotherapy that attacks both cancerous and healthy cells, BMS-986484 works by targeting specific pathways in tumor cells, potentially reducing side effects. Nivolumab, an immune checkpoint inhibitor, enhances the immune system's ability to recognize and destroy cancer cells. This combination aims to deliver a double punch: directly inhibiting tumor growth while simultaneously boosting the body's natural defenses. Such a strategy could lead to more effective and less toxic cancer treatments compared to current options.

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

Research shows that BMS-986484, one of the treatments in this trial, has demonstrated early signs of effectiveness with a manageable safety profile. In this trial, some participants will receive BMS-986484 alone, while others will receive it combined with nivolumab. Studies have found that combining BMS-986484 with nivolumab may enhance its effectiveness, particularly for treating solid tumors. Nivolumab, another treatment option in this trial, is already approved for conditions like non-small cell lung cancer and aids the immune system in fighting cancer. Additionally, some trial participants will receive a combination of BMS-986484, nivolumab, and chemotherapy, which early results suggest might further improve treatment outcomes. While more research is needed, these combinations appear promising for treating advanced cancers. ^{1 2 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 people with advanced solid tumors, including lung, colorectal, pancreatic, stomach/esophageal, and head/neck cancers. Participants must have a tumor that hasn't responded to standard treatments or has come back.

Inclusion Criteria

Must have measurable disease by response evaluation criteria in solid tumors version 1.1 (RECIST v1.1)

I am fully active or restricted in physically strenuous activity but can do light work.

My cancer is advanced and cannot be removed by surgery.

Exclusion Criteria

I have an autoimmune disease.

I have or had lung scarring or interstitial lung disease.

I do not have any serious uncontrolled medical conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BMS-986484 alone or in combination with nivolumab to assess safety and tolerability

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BMS-986484
• Nivolumab

Trial Overview The study tests BMS-986484 alone and combined with Nivolumab in patients with certain types of cancer. It aims to find out how safe these drugs are and how well they work together.

How Is the Trial Designed?

Group I: Part 2C: BMS-986484 + Nivolumab + Chemotherapy Dose Expansion Experimental Treatment 6 Interventions

Group II: Part 2B: BMS-986484 + Nivolumab Dose Expansion Experimental Treatment 2 Interventions

Group III: Part 2A: BMS-986484 Dose Expansion Experimental Treatment 1 Intervention

Group IV: Part 1SC: BMS-986484 Monotherapy Subcutaneous Dose Escalation Experimental Treatment 1 Intervention

Group V: Part 1C: BMS-986484 + Nivolumab + Chemotherapy Dose Escalation Experimental Treatment 6 Interventions

Group VI: Part 1B: BMS-986484 + Nivolumab Dose Escalation Experimental Treatment 2 Interventions

Group VII: Part 1A: BMS-986484 Dose Escalation Experimental Treatment 1 Intervention

Group VIII: Part 1 Co-Admin: BMS-986484 + Nivolumab Experimental Treatment 2 Interventions

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

In a phase 2 trial involving 117 patients with advanced, refractory squamous non-small-cell lung cancer, nivolumab demonstrated a 14.5% objective response rate, indicating its potential effectiveness as a treatment option.

The safety profile of nivolumab was manageable, with 17% of patients experiencing severe treatment-related adverse events, suggesting that while there are risks, the benefits may outweigh them for patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Rizvi, NA., Mazières, J., Planchard, D., 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 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 of 45 patients with metastatic melanoma treated with the combination of nivolumab and ipilimumab, the disease control rate was 54% and the objective response rate was 29%, indicating moderate efficacy in a real-world setting.

The treatment had a high toxicity profile, with 88% of patients experiencing adverse events, and 44% discontinuing treatment due to these events, highlighting the need for careful monitoring and management of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world efficacy and toxicity of combined nivolumab and ipilimumab in patients with metastatic melanoma. Parakh, S., Randhawa, M., Nguyen, B., et al.[2019]

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]

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]

BMS-986148, a mesothelin-directed antibody-drug conjugate, showed a manageable safety profile in a phase I/IIa study with 126 patients, with common treatment-related adverse events including increased liver enzymes.

Preliminary evidence of clinical activity was observed with BMS-986148 alone and in combination with nivolumab, suggesting potential for further studies on combining targeted therapies with immune checkpoint inhibitors in advanced solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/IIa Trial of BMS-986148, an Anti-mesothelin Antibody-drug Conjugate, Alone or in Combination with Nivolumab in Patients with Advanced Solid Tumors. Rottey, S., Clarke, J., Aung, K., et al.[2023]

Nivolumab and pembrolizumab, both PD-1 inhibitors, show a lower risk of severe treatment-related adverse effects (AEs) compared to standard care, with a relative risk of 0.39 for grade 3/4 AEs based on a meta-analysis of 9 trials involving 5,353 patients.

While these therapies are generally well tolerated, they are associated with a significantly increased risk of thyroid dysfunction (hyperthyroidism and hypothyroidism) and skin conditions like pruritus and vitiligo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity profile of approved anti-PD-1 monoclonal antibodies in solid tumors: a systematic review and meta-analysis of randomized clinical trials. Costa, R., Carneiro, BA., Agulnik, M., et al.[2022]

Nivolumab and pembrolizumab are FDA-approved monoclonal antibodies that target PD-1, helping to enhance T cell activity against cancer by blocking the PD-1/PD-L1 interaction, which allows cancer cells to escape immune detection.

Both drugs have shown efficacy across multiple cancer types, including melanoma and non-small cell lung cancer, and are considered interchangeable options for treating these conditions, which may help manage the rising costs of cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. Prasad, V., Kaestner, V.[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]

Citations

1. bmsstudyconnect.com bmsstudyconnect.com/mx/en/clinical-trials/NCT06544655.html

A Study of BMS-986484 Alone and Combination Therapy in ... The purpose of this study is to assess the safety and tolerability of BMS-986484 administered alone, in combination with nivolumab in participants with ...

2. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/525816

A Study of BMS-986484 Alone and Combination Therapy ... The purpose of this study is to assess the safety and tolerability of BMS-986484 administered alone, in combination with nivolumab in ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9401510/

Phase I/IIa Trial of BMS-986148, an Anti-mesothelin Antibody ... BMS-986148 ± nivolumab demonstrated a clinically manageable safety profile and preliminary evidence of clinical activity.

4. tipranks.com tipranks.com/news/company-announcements/bristol-myers-squibbs-new-cancer-study-a-potential-game-changer

Bristol-Myers Squibb's New Cancer Study: A Potential ... ' The study aims to evaluate the safety and tolerability of BMS-986484, both alone and in combination with nivolumab, in patients with advanced ...

5. bms.com bms.com/assets/bms/us/en-us/pdf/investor-info/doc_presentations/2024/BMY-2024-Q3-Results-Investor-Presentation-with-Appendix.pdf

Q3 2024 Results Presentation (with Appendix) • Phase 1 - EGFR x HER3 ADC in solid tumors (2025)3. • Phase 2 ... BMS-986484. ✦ Solid Tumors. EGFRxHER3 ADC. ✦ 1L Non-Small Cell Lung ...

6. cancer.gov cancer.gov/clinicaltrials/NCI-2024-10044

A Study of BMS-986484 Alone and Combination Therapy ... The purpose of this study is to assess the safety and tolerability of BMS-986484 administered alone, in combination with nivolumab in participants with ...

7. trials.braintumor.org trials.braintumor.org/trials/NCT06544655

A Study of BMS-986484 Alone and Combination Therapy in ... A Study of BMS-986484 Alone and Combination Therapy in Participants With Advanced Solid Tumors. Study Purpose. The purpose of this study is to assess the safety ...

8. theglobeandmail.com theglobeandmail.com/investing/markets/stocks/BMY/pressreleases/33498167/bristol-myers-squibbs-promising-clinical-trial-for-advanced-solid-tumors/

Bristol-Myers Squibb's Promising Clinical Trial for ... The study aims to evaluate the safety and tolerability of BMS-986484, alone and in combination with nivolumab, in patients with advanced solid ...