BMS-986482 for Cancer

Recruiting at 23 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

Disqualifiers: Life threatening immune toxicity, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

413 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to test the safety and efficacy of BMS-986482 alone and as combination therapy in participants with advanced solid tumors.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the study team for guidance.

What data supports the effectiveness of the drug BMS-986482 for cancer?

Nivolumab, a component of BMS-986482, has shown effectiveness in treating advanced cancers like melanoma and non-small cell lung cancer by improving survival rates and being better tolerated than some other treatments. Additionally, the combination of nivolumab and relatlimab has been approved for treating advanced melanoma, indicating its potential effectiveness in cancer treatment. ^{1 2 3 4 5}

What is the safety profile of BMS-986482 (Nivolumab, Opdivo, Relatlimab, Opdualag, BMS-986016, relatlimab-rmbw, rHuPH20) in humans?

Nivolumab, a component of BMS-986482, has been studied in various clinical trials and is generally considered safe, but it can cause side effects like fatigue, rash, itching, diarrhea, nausea, and weakness. Serious side effects are less common but can include low phosphate levels and low white blood cell counts. There is also a risk of hepatitis B reactivation in patients treated with PD-1/PD-L1 inhibitors like Nivolumab. ^{1 6 7 8 9}

How is the drug BMS-986482 different from other cancer treatments?

BMS-986482 is unique because it is a combination of two immunotherapy drugs, nivolumab and relatlimab, which target different immune checkpoints to help the body's immune system fight cancer. Nivolumab targets the PD-1 receptor, while relatlimab targets the LAG-3 protein, making this combination a novel approach compared to other treatments that may only target one checkpoint. ^{1 2 3 5 9}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This clinical trial is open to individuals with advanced solid tumors. Specific eligibility criteria are not provided, but typically participants must have a certain type and stage of cancer, meet health condition requirements, and may need to have tried other treatments first.

Inclusion Criteria

My cancer is advanced, cannot be surgically removed, and does not respond to current treatments.

I have one of the specified types of cancer.

I can provide a recent tumor sample for the study.

Exclusion Criteria

Other protocol-defined Inclusion/Exclusion criteria apply

I've had severe immune reactions from previous cancer treatments that won't happen again with proper care.

I do not have any major health issues that could 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-986482 alone or in combination therapy for advanced solid tumors

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Nivolumab
• Relatlimab
• rHuPH20

Trial Overview The study is testing the safety and effectiveness of BMS-986482 both alone and in combination with other therapies (Nivolumab and rHuPH20, Nivolumab/relatlimab/rHuPH20, Bevacizumab) for treating advanced solid tumors.

Participant Groups

Group I: Part 2B3 Experimental Treatment 2 Interventions

Group II: Part 2B2 Experimental Treatment 2 Interventions

Group III: Part 2B1 Experimental Treatment 2 Interventions

Group IV: Part 2A Experimental Treatment 1 Intervention

Group V: Part 1C Experimental Treatment 1 Intervention

Group VI: Part 1B3 Experimental Treatment 2 Interventions

Group VII: Part 1B2 Experimental Treatment 2 Interventions

Group VIII: Part 1B1 Experimental Treatment 2 Interventions

Group IX: Part 1A 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 plus relatlimab is a combination immunotherapy that targets immune checkpoints, specifically PD-1 and LAG-3, and has been approved for treating unresectable or metastatic melanoma in adults and adolescents weighing at least 40 kg.

This combination therapy represents a significant advancement in cancer treatment, as it utilizes two different mechanisms to enhance the immune response against cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Plus Relatlimab: First Approval. Paik, J.[2022]

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]

Nivolumab (Opdivo) monotherapy led to complete regression of local recurrence and multiple lung metastases in a patient with recurrent skin melanoma and a positive BRAF mutation, demonstrating its efficacy as a treatment option.

After 5 courses of nivolumab, the patient experienced significant improvement in her condition, achieving an ECOG performance status of 0, indicating a return to an active lifestyle without pain, and normal serum LDH levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[EVALUATION OF THE EFFICASY OF THE DRUG OPDIVO (NIVOLUMAB) IN A PATIENT DIAGNOSED WITH UNRESECTABLE SKIN MELANOMA, POSITIVE BRAF MUTATION AND DISEASE DISSEMINATION (CASE REPORT)]. Samsonia, M., Kandelaki, M., Gibradze, O., et al.[2021]

Relatlimab, when used in combination with nivolumab, is an approved first-line treatment for metastatic or unresectable melanoma, enhancing the immune response against cancer cells.

The review highlights the mechanism of action and safety profile of this combination therapy, emphasizing its clinical efficacy based on recent studies and ongoing trials, making it a significant option for dermatologists treating melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relatlimab-nivolumab: A practical overview for dermatologists. Mullick, N., Nambudiri, VE.[2023]

A retrospective analysis of adverse events related to PD-1/PD-L1 inhibitors revealed a significant association between Pembrolizumab and hepatitis B reactivation (HBVr), with a reporting odds ratio of 2.32, indicating a higher risk compared to other treatments.

No cases of HBVr were reported with Ipilimumab or Avelumab, suggesting that not all immune checkpoint inhibitors carry the same risk, highlighting the need for further prospective studies to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatitis B Virus Reactivation in Cancer Patients Treated With Immune Checkpoint Inhibitors. Burns, EA., Muhsen, IN., Anand, K., et al.[2023]

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]

In a meta-analysis of 4413 patients from 8 randomized controlled trials, PD-1/PD-L1 inhibitors showed a significantly lower risk of all-grade adverse events (66.20% vs. 86.08%) and high-grade adverse events (14.26% vs. 43.53%) compared to chemotherapy, indicating a better safety profile.

While PD-1/PD-L1 inhibitors are generally safer, they are associated with a unique set of immune-related adverse events (irAEs) that can be severe, such as pneumonitis and thyroid dysfunction, which clinicians need to monitor closely to manage patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer: a meta-analysis of randomized controlled trials. Luo, W., Wang, Z., Tian, P., et al.[2021]

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]

References

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

Nivolumab Plus Relatlimab: First Approval. [2022]

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

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

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

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

4. Georgia (Republic) pubmed.ncbi.nlm.nih.gov

[EVALUATION OF THE EFFICASY OF THE DRUG OPDIVO (NIVOLUMAB) IN A PATIENT DIAGNOSED WITH UNRESECTABLE SKIN MELANOMA, POSITIVE BRAF MUTATION AND DISEASE DISSEMINATION (CASE REPORT)]. [2021]

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

Relatlimab-nivolumab: A practical overview for dermatologists. [2023]

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

Hepatitis B Virus Reactivation in Cancer Patients Treated With Immune Checkpoint Inhibitors. [2023]

7. 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]

8. Germany pubmed.ncbi.nlm.nih.gov

Safety and tolerability of PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer: a meta-analysis of randomized controlled trials. [2021]

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

Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. [2022]