BMS-986218 + Nivolumab for Cancer

No longer recruiting at 112 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and tolerability of a new treatment, BMS-986218 (an experimental treatment), both alone and in combination with Nivolumab, for advanced solid tumors. The study aims to determine if these treatments can help individuals whose cancer has progressed after at least two standard therapies. Participants should have advanced solid tumors such as melanoma, non-small cell lung cancer, or microsatellite stable colorectal cancer and have experienced treatment relapses or intolerance. This trial offers a chance to potentially benefit from cutting-edge treatments while contributing to cancer research. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, providing participants the opportunity to be among the first to receive this new treatment.

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.

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

Research has shown that BMS-986218 is generally well-tolerated by patients. Studies have found it has a manageable safety profile both alone and in combination with Nivolumab. This combination is under investigation because both drugs enhance the immune system's ability to fight cancer.

Some side effects have been reported, typically mild to moderate, and similar to those seen with other immune-boosting cancer treatments. Notably, the FDA has already approved Nivolumab for other cancers, indicating its safety is well-understood in various contexts.

While BMS-986218 remains under study, evidence so far suggests it might be safe for patients with advanced solid tumors. However, individual differences exist, so discussing potential risks with healthcare providers before joining a trial is crucial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BMS-986218 combined with Nivolumab for cancer treatment because this combination offers a novel approach compared to standard therapies. Unlike traditional treatments that mainly attack cancer cells directly, BMS-986218 operates by enhancing the body's immune response to target and destroy cancer cells. This is achieved through a mechanism known as immune checkpoint inhibition, which helps the immune system recognize and attack cancer cells more effectively. Additionally, when combined with Nivolumab, another immune checkpoint inhibitor, the treatment has the potential to provide a more robust and sustained anti-cancer response, giving hope for better outcomes in cases where other treatments might not have been effective.

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

Research shows that BMS-986218 holds promise for treating advanced solid tumors. Studies have found it safe and observed early signs of tumor size reduction when used alone. In this trial, some participants will receive BMS-986218 as monotherapy, while others will receive it in combination with Nivolumab, a well-known cancer drug that enhances the immune system's ability to locate and attack tumors. Research suggests that BMS-986218 targets specific immune cells in tumors, potentially boosting the body's natural cancer-fighting ability. Although more information is needed, these findings suggest it could be effective for certain 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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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, 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]

Citations

1. jitc.bmj.com jitc.bmj.com/content/10/Suppl_2/A620

592 Phase 1/2a study of the novel nonfucosylated anti– ... BMS-986218 demonstrated a tolerable safety profile and preliminary antitumor activity as monotherapy and in combination with nivolumab across various tumor ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04301414

Study Details | NCT04301414 | Non-fucosylated Anti-CTLA ... The purpose of this study is to see whether immunotherapy with BMS-986218 added to degarelix (which suppresses testosterone) given prior to surgery can ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11419205/

Fc-enhanced anti-CTLA-4 depletes tumor-infiltrating ... Mechanistic studies indicated BMS-986218 depleted TI-Tregs by engaging CD16a/FCGR3A on tumor macrophages, modulated dendritic cells (DCs), and ...

4. withpower.com withpower.com/trial/phase-2-4-2017-d957c

BMS-986218 + Nivolumab for Cancer · Info for Participants 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 ...

5. researchgate.net researchgate.net/publication/346801247_393_First-in-human_phase_12a_study_of_the_novel_nonfucosylated_anti-CTLA-4_monoclonal_antibody_BMS-986218_nivolumab_in_advanced_solid_tumors_initial_phase_1_results

(PDF) 393 First-in-human phase 1/2a study of the novel ... Conclusions BMS-986218 monotherapy demonstrated an acceptable safety profile and signs of clinical benefit in this heterogeneous patient ...

6. synapse.patsnap.com synapse.patsnap.com/article/assessing-the-safety-of-second-generation-anti-ctla4-variants-in-primate-models

Assessing the Safety of Second-Generation Anti-CTLA4 ... BMS-986218 is modified to bind more strongly to immune cells and might help fight cancer better by removing some immune cells in the tumor. BMS- ...

7. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03110107/

Clinical Trial: NCT03110107 The purpose of this study is to determine whether a Monoclonal Antibody both by itself and in combination with Nivolumab is safe and ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04785287

Anti-CTLA4-NF mAb (BMS986218), Nivolumab, and ... Giving -CTLA4-NF mAb (BMS986218), nivolumab, and stereotactic body radiation therapy may kill more tumor cells. Detailed Description. PRIMARY OBJECTIVE: I. To ...