BMS-986449 + Nivolumab for Advanced Cancer

Recruiting at 37 trial locations

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

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Bristol-Myers Squibb

Must not be taking: T-cell agonists, Checkpoint inhibitors

Disqualifiers: Gastrointestinal disease, Significant medical illness, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

100 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the safety and efficacy of BMS-986449 alone and in combination with nivolumab in participants with advanced solid tumors.

Do I have to stop taking my current medications for the trial?

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-986449 + Nivolumab for advanced cancer?

Nivolumab, a part of the treatment, has shown significant improvement in survival rates and response in patients with advanced squamous non-small cell lung cancer, as seen in the CheckMate 017 trial. Additionally, combining nivolumab with other treatments has been associated with improved responses in different cancers, suggesting potential effectiveness in advanced cancer. ^{1 2 3 4 5}

What is known about the safety of BMS-986449 and Nivolumab in humans?

Nivolumab, also known as Opdivo, is generally well-tolerated in humans, but it can cause immune-related side effects, which are manageable. There is no specific safety data available for BMS-986449, but similar treatments have been evaluated for safety in combination with Nivolumab in patients with advanced solid tumors. ^{4 6 7 8 9}

What makes the drug BMS-986449 + Nivolumab unique for advanced cancer?

The combination of BMS-986449 and Nivolumab is unique because it involves a novel approach using an OX40 agonist (a type of protein that can enhance the immune response) with a PD-1 inhibitor (a drug that helps the immune system attack cancer cells), potentially offering a new way to boost the body's immune response against advanced cancers. ^{4 7 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 (metastatic), and who haven't responded to, can't receive, or had adverse reactions to standard treatments. Part of the study focuses on those with specific cancers like non-small cell lung cancer and triple-negative breast cancer.

Inclusion Criteria

I have tried or cannot take current treatments for my condition.

My cancer is advanced, cannot be surgically removed, and can be measured for changes.

I have non-small cell lung cancer.

Exclusion Criteria

I've had severe side effects from previous immune therapy.

I have had recent stomach or intestine problems or surgery that could affect how I absorb medication.

I do not have any major health issues that would affect my participation in the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BMS-986449 alone or in combination with nivolumab to evaluate safety and efficacy

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• BMS-986449
• Nivolumab

Trial Overview The study is testing BMS-986449 both alone and combined with Nivolumab to see how safe they are and if they work in treating various advanced solid tumors. Participants will be given these drugs to assess their effectiveness against the tumors.

Participant Groups

Group I: Dose Escalation: BMS-986449 monotherapy pharmacodynamic (PD) cohorts Experimental Treatment 1 Intervention

Group II: Dose Escalation: BMS-986449 monotherapy Experimental Treatment 1 Intervention

Group III: Dose Escalation: BMS-986449 + 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

Findings from Research

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]

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]

Combining nivolumab with ipilimumab results in higher response rates in cancer treatment compared to using nivolumab alone, indicating a potentially more effective therapeutic strategy.

This combination therapy may enhance the immune response against cancer, but specific details on the number of subjects or study duration are not provided in the abstract.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus Ipilimumab Achieves Responses in dMMR/MSI-H Tumors. [2019]

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]

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]

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, a monoclonal antibody used to treat recurrent renal cell carcinoma, can cause significant immune-related adverse events, such as hepatitis and adrenalitis, as seen in a case study of a 66-year-old male patient.

Prompt recognition and management of these side effects are crucial; in this case, the patient's hepatitis improved with methylprednisolone, and adrenalitis was treated with fludrocortisone, leading to normalization of symptoms and electrolyte levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side effects of immune-checkpoint inhibitors: Can multiple side effects be seen in a patient? Özyurt, E., Özçelik, S., Sürmeli, H., et al.[2022]

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 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]

Nivolumab, a PD-1 inhibitor, has demonstrated significant safety and efficacy in treating various advanced solid tumors, including melanoma and lung cancer, based on multiple high-level studies.

Future research should aim to identify predictive biomarkers for treatment response and explore the potential of combining nivolumab with other therapies, as well as determining the best treatment strategies and duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the pharmacodynamics, pharmacokinetics, safety and clinical efficacy of nivolumab in the treatment of solid cancers. Wong, AC., Ma, B.[2018]

Nivolumab, a targeted cancer therapy, can lead to rare cutaneous side effects such as plaque morphea, as demonstrated in a case study of a 48-year-old female patient with metastatic melanoma.

The plaque morphea lesion responded well to treatment with topical corticosteroids and calcipotriol, highlighting the importance of monitoring for less common skin reactions in patients receiving PD-1 inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab-induced plaque morphea in a malign melanoma patient. Acar, A., Oraloglu, G., Yaman, B., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

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

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

Bempegaldesleukin Ups Melanoma Responses. [2020]

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

Nivolumab plus Ipilimumab Achieves Responses in dMMR/MSI-H Tumors. [2019]

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

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

5. England pubmed.ncbi.nlm.nih.gov

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

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. 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]

8. England pubmed.ncbi.nlm.nih.gov

Side effects of immune-checkpoint inhibitors: Can multiple side effects be seen in a patient? [2022]

9. United States 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. [2022]

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. England pubmed.ncbi.nlm.nih.gov

An update on the pharmacodynamics, pharmacokinetics, safety and clinical efficacy of nivolumab in the treatment of solid cancers. [2018]

12. England pubmed.ncbi.nlm.nih.gov

Nivolumab-induced plaque morphea in a malign melanoma patient. [2021]