BMS-986482 for Cancer

Recruiting at 28 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called BMS-986482, both alone and in combination with other drugs, to assess its safety and effectiveness for people with advanced solid tumors (cancers that form solid masses). The study includes different groups testing the treatment in various combinations. Individuals with advanced cancer that cannot be surgically removed, and who have not responded to other treatments, might be suitable candidates for this trial. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

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.

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

A previous study showed that nivolumab provides long-term benefits for patients with advanced melanoma, with many experiencing lasting survival. This suggests the treatment is generally well-tolerated for serious conditions. However, some patients reported side effects, such as tiredness, skin rash, and more serious immune-related reactions.

Research indicates that combining nivolumab and relatlimab carries a higher risk of significant side effects compared to nivolumab alone. Common side effects include skin reactions and tiredness, but these are mostly manageable. The safety profile aligns with known data about each drug individually.

Studies have found rHuPH20 to be generally safe, with no negative effects on fertility or development, indicating it is safe when used with other treatments.

Overall, these treatments have been studied for their safety, but like all medications, they may cause side effects. Clinical trial participants are closely monitored to ensure their safety and to manage any side effects that occur. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the investigational treatments Nivolumab, Relatlimab, and rHuPH20 for cancer because they offer a unique approach compared to standard therapies like chemotherapy and radiation. Nivolumab and Relatlimab are monoclonal antibodies that work by enhancing the body's immune response against cancer cells. Nivolumab targets the PD-1 pathway, while Relatlimab targets the LAG-3 pathway, both crucial in immune checkpoint inhibition. rHuPH20, on the other hand, enhances the delivery of these therapies by breaking down hyaluronan, a substance that can create barriers around tumors. This combination aims to improve the effectiveness and delivery of immunotherapy, offering a potentially more robust and targeted attack on cancer cells.

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

Research has shown that nivolumab, one of the treatments in this trial, effectively treats advanced cancers like melanoma and lung cancer. Studies have found that patients treated with nivolumab experience better long-term survival rates, with some trials reporting that 34.2% of patients survive for five years. In this trial, some participants will receive a combination of nivolumab and relatlimab, which has significantly extended the time patients live without their disease worsening. Meanwhile, rHuPH20, another treatment option in this trial, is under study for its potential to enhance the delivery of medicine under the skin. Overall, these treatments have shown promise in managing advanced tumors by improving survival and treatment effectiveness. ^{3 4 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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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, 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]

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]

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]

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 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 (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]

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, 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7699139/

Real-World, Long-Term Outcomes of Nivolumab Therapy ... Studies in lung cancer and renal cell carcinoma indicate that response to ICIs is associated with survival, [15,16] suggesting that overall response may be a ...

2. opdivohcp.com opdivohcp.com/efficacy

Efficacy Information | OPDIVO® (nivolumab) In NSCLC patients receiving OPDIVO 3 mg/kg every 2 weeks with YERVOY 1 mg/kg every 6 weeks, immune-mediated pneumonitis occurred in 9% (50/576) of patients, ...

3. news.bms.com news.bms.com/news/details/2021/Six-and-a-Half-Year-Outcomes-for-Opdivo-nivolumab-in-Combination-with-Yervoy-ipilimumab-Continue-to-Demonstrate-Durable-Long-Term-Survival-Benefits-in-Patients-with-Advanced-Melanoma/default.aspx

Six-and-a-Half-Year Outcomes for Opdivo (nivolumab) in ... With a minimum follow-up of 6.5 years, median overall survival (OS) was 72.1 months with Opdivo plus Yervoy (95% CI: 38.2-NR), the longest ...

4. opdivo.com opdivo.com/clinical-trial-results

Clinical Trial Results Select your cancer type above to see how OPDIVO, alone or in combination with other therapies, performed in clinical trials.

5. hopkinsmedicine.org hopkinsmedicine.org/news/newsroom/news-releases/2019/07/favorable-five-year-survival-reported-for-patients-with-advanced-cancer-treated-with-the-immunotherapy-drug-nivolumab

Favorable Five-Year Survival Reported For Patients With ... By comparison, the results with nivolumab, reported July 25 in JAMA Oncology, show higher than expected rates of five-year survival: 34.2% for ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12290226/

Evaluation of safety outcomes between nivolumab ... Real-world safety outcomes between the two flat-dose nivolumab regimens demonstrated to be similar in a study of adjuvant nivolumab recipients ...

7. jto.org jto.org/article/S1556-0864(24)02355-4/fulltext

Long-Term Survival Outcomes With First-Line Nivolumab ... Nivolumab plus ipilimumab–based treatment regimens have shown long-term, durable efficacy benefits in patients with metastatic NSCLC.

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.22.01503

Five-Year Survival Outcomes With Nivolumab Plus ... We present 5-year results from CheckMate 227 Part 1, in which nivolumab plus ipilimumab improved overall survival (OS) versus chemotherapy ...