BMS-986488 for Cancer

Recruiting at 11 trial locations

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

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Bristol-Myers Squibb

Disqualifiers: CNS metastases, Cardiac disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

437 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug BMS-986488, Nivolumab for cancer?

Nivolumab, one of the drugs in the treatment, has shown effectiveness in improving survival and quality of life in patients with metastatic melanoma and recurrent squamous-cell carcinoma of the head and neck. It also helps control disease in advanced non-small cell lung cancer. ^{1 2 3 4 5}

Is BMS-986488 (Nivolumab) generally safe for humans?

Nivolumab, also known as BMS-986488, has been studied in many clinical trials and is generally considered safe, but it can cause side effects. Common side effects include tiredness, skin rash, itching, diarrhea, nausea, and weakness. Serious side effects are less common but can include low phosphate levels and low white blood cell counts. ^{5 6 7 8 9}

What makes the drug BMS-986488 unique for cancer treatment?

BMS-986488 is unique because it combines with nivolumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, potentially offering a novel approach for treating cancers that may not respond well to standard therapies. ^{1 5 6 10 11}

What is the purpose of this trial?

This purpose of this study is to determine if experimental treatment with BMS-986488, alone, or in combinations is safe, tolerable, and has anti-cancer activity in patients with advanced malignant tumors.

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This trial is for individuals with advanced malignant tumors who are seeking new treatment options. Specific eligibility criteria details were not provided, so interested participants should inquire further to determine if they meet the inclusion and exclusion requirements.

Inclusion Criteria

I am fully active or can carry out light work.

Participants must have measurable disease per RECIST v1.1

My cancer is advanced, cannot be surgically removed, and is of a specific type.

Exclusion Criteria

I have had pneumonitis or lung disease in the past.

My brain metastases have not been treated.

I have heart problems that affect my daily activities.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BMS-986488 as monotherapy or in combination with other drugs to assess safety, tolerability, and anti-cancer activity

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

52 weeks

Treatment Details

Interventions

• BMS-986488
• Nivolumab

Trial Overview The study is testing BMS-986488 as a single agent and in combination with other cancer drugs: Adagrasib, Nivolumab, and Cetuximab. It aims to assess safety, tolerability, and effectiveness against cancer.

Participant Groups

Group I: Part 2D: BMS-986488 + Nivolumab Experimental Treatment 2 Interventions

Group II: Part 2C: BMS-986488 + Adagrasib + Cetuximab Experimental Treatment 3 Interventions

Group III: Part 2B: BMS-986488 + Adagrasib Experimental Treatment 2 Interventions

Group IV: Part 2A: BMS-986488 Monotherapy Experimental Treatment 1 Intervention

Group V: Part 1D: BMS-986488 + Nivolumab Experimental Treatment 2 Interventions

Group VI: Part 1C: BMS-986488 + Adagrasib + Cetuximab Experimental Treatment 3 Interventions

Group VII: Part 1B: BMS-986488 + Adagrasib Experimental Treatment 2 Interventions

Group VIII: Part 1A: BMS-986488 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 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]

In a study of 88 patients with metastatic melanoma, higher serum concentrations of nivolumab were significantly correlated with better clinical outcomes, including overall and progression-free survival.

Patients who achieved a clinical response not only had higher nivolumab levels but also exhibited a distinct genetic profile with increased activation of genes related to T-cell activation, suggesting that both drug concentration and genetic factors may influence treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab serum concentration in metastatic melanoma patients could be related to outcome and enhanced immune activity: a gene profiling retrospective analysis. Mallardo, D., Giannarelli, D., Vitale, MG., et al.[2023]

Nivolumab treatment resulted in an increased overall survival rate of 7.5 months compared to 5.1 months for the control group, indicating its efficacy in extending life for patients.

Patients receiving nivolumab also reported a better quality of life, suggesting that the treatment not only prolongs survival but also improves the well-being of those undergoing therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab for recurrent squamous-cell carcinoma of the head and neck. [2018]

In a study of 66 patients with advanced non-small cell lung cancer (NSCLC) treated with nivolumab, those with a poor performance status (PS ≥2) had a significantly shorter median overall survival of 3.04 months compared to 10.23 months for those with better performance status (PS ≤1).

Despite similar rates of treatment-related adverse events between the two groups, the findings suggest that performance status is a crucial factor in predicting survival outcomes and should be considered when selecting immunotherapy treatments for lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience of nivolumab in the treatment of poor performance status patients with advanced non-small cell lung cancer. Abbas, MN., Klevansky, M., Koczwara, B., 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]

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, an immune checkpoint inhibitor, shows strong antitumor activity but is associated with immune-related adverse events that can affect patient safety and treatment continuation, necessitating careful monitoring.

Long-term safety data, including a 5-year follow-up, suggests that nivolumab can be safely administered to various challenging patient subgroups, but identifying biomarkers for severe toxicity could improve patient selection for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the safety of nivolumab for the treatment of advanced melanoma. Czarnecka, AM., Rutkowski, P.[2021]

Nivolumab, an immune checkpoint inhibitor, shows a low rate of severe adverse effects (grade ≥3 AEs at 12%) and a very low mortality rate (0.25%), indicating it is a relatively safe treatment option for cancer patients.

In terms of efficacy, nivolumab demonstrates better treatment responses and survival rates compared to traditional chemotherapy, with a 1-year overall survival rate of 52% and a significantly higher objective response rate (ORR) of 26%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of nivolumab in the treatment of cancers: A meta-analysis of 27 prospective clinical trials. Tie, Y., Ma, X., Zhu, C., et al.[2022]

The combination of nivolumab and relatlimab shows a manageable safety profile for patients with advanced melanoma who have already undergone treatment.

This combination therapy may offer a new option for patients with pretreated melanoma, suggesting potential efficacy in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Plus Relatlimab Is Safe and Efficacious in Pretreated Melanoma. [2023]

In the CheckMate 358 trial, nivolumab showed promising efficacy in patients with recurrent/metastatic cervical cancer, achieving an objective response rate of 26.3% and a median overall survival of 21.9 months, indicating its potential as a treatment option.

The treatment was generally well-tolerated, with 63.2% of cervical cancer patients experiencing any-grade treatment-related adverse events, but no treatment-related deaths were reported, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Nivolumab Monotherapy in Recurrent or Metastatic Cervical, Vaginal, or Vulvar Carcinoma: Results From the Phase I/II CheckMate 358 Trial. Naumann, RW., Hollebecque, A., Meyer, T., et al.[2021]

References

1. 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]

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

Nivolumab serum concentration in metastatic melanoma patients could be related to outcome and enhanced immune activity: a gene profiling retrospective analysis. [2023]

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

Nivolumab for recurrent squamous-cell carcinoma of the head and neck. [2018]

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

Real-world experience of nivolumab in the treatment of poor performance status patients with advanced non-small cell lung cancer. [2022]

5. 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]

6. United States 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. [2023]

7. England pubmed.ncbi.nlm.nih.gov

An update on the safety of nivolumab for the treatment of advanced melanoma. [2021]

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

Safety and efficacy of nivolumab in the treatment of cancers: A meta-analysis of 27 prospective clinical trials. [2022]

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

Nivolumab Plus Relatlimab Is Safe and Efficacious in Pretreated Melanoma. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Real-life results from the overall population and key subgroups within the Italian cohort of nivolumab expanded access program in non-squamous non-small cell lung cancer. [2020]

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

Safety and Efficacy of Nivolumab Monotherapy in Recurrent or Metastatic Cervical, Vaginal, or Vulvar Carcinoma: Results From the Phase I/II CheckMate 358 Trial. [2021]