BMS-986253 + Immunotherapy for Advanced Cancer

Not currently recruiting at 177 trial locations

Overseen By BMS Study Connect Contact Center www.BMSStudyConnect.com

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Bristol-Myers Squibb

Must not be taking: Corticosteroids, Immunosuppressives, Cytotoxic agents

Disqualifiers: CNS metastases, Autoimmune disease, HIV/AIDS, others

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called BMS-986253, combined with the immunotherapy drugs Nivolumab and Ipilimumab, to determine its effectiveness for people with advanced cancers. The study includes different groups to assess how well these drugs work together. Individuals with certain types of solid tumors that have spread or cannot be removed might be suitable candidates, especially if they have a measurable and biopsy-accessible tumor. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering 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 must stop all current medications, but you cannot take certain immunosuppressive medications or corticosteroids above a certain dose within 14 days of starting the study. Also, if you are on cytotoxic agents, you need to wait at least 4 weeks after your last dose before starting the trial.

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

Earlier studies found that the combination of BMS-986253 and nivolumab was generally well-tolerated by patients with advanced cancer. Some side effects, such as tiredness and nausea, were noted, but most participants managed them.

When BMS-986253 is combined with both nivolumab and ipilimumab, the safety profile remains similar. However, adding ipilimumab can increase the risk of more serious side effects, such as immune system reactions, which are already known risks with these drugs.

Nivolumab and ipilimumab are approved for treating other cancers, indicating a known safety record. BMS-986253 is still being studied in early trials, so its safety is still under evaluation, but initial results suggest it is tolerated similarly to other treatments in its category.

Overall, while possible side effects exist, the treatment appears safe enough for further research. Participants should always discuss the risks and benefits with their healthcare provider before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BMS-986253 because it offers a new approach to treating advanced cancer by targeting IL-8, a molecule involved in cancer growth and immune suppression. Unlike current treatments, which often focus on blocking PD-1 or CTLA-4 pathways, BMS-986253 works in combination with immunotherapies like nivolumab and ipilimumab to potentially boost the immune system's ability to fight cancer. This unique mechanism has the potential to enhance the effectiveness of existing checkpoint inhibitors, potentially leading to better outcomes for patients with advanced cancer.

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

Research shows that BMS-986253 targets IL-8, a molecule that can make cancer harder to treat. Early studies suggest that blocking IL-8 might help make tumors less aggressive and more responsive to treatment. In this trial, some participants will receive BMS-986253 combined with Nivolumab, a drug that helps the immune system fight cancer. This combination has shown promising results in early studies for patients with advanced cancer. Other participants will receive a combination of Nivolumab and Ipilimumab, another drug that boosts the immune system. Although adding Ipilimumab did not significantly help patients with advanced melanoma who had previous treatments, the combination of Nivolumab and Ipilimumab alone has shown survival benefits in other types of cancer. ^{1 2 3 4 5}

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 are physically capable of daily activity or light work. They must have a tumor that can be measured and one that's reachable for biopsy. People taking high-dose steroids, recent cytotoxic agents, those with HIV/AIDS, or active autoimmune diseases cannot join.

Inclusion Criteria

I am fully active or can carry out light work.

My cancer has spread, cannot be surgically removed, and can be measured by scans.

I have a tumor that can be biopsied.

Exclusion Criteria

I have brain metastases but they are under control.

You have an ongoing autoimmune disease.

It's been over 4 weeks since my last cancer treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BMS-986253 in combination with Nivolumab or Nivolumab plus Ipilimumab

Approximately 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BMS-986253
• Ipilimumab
• Nivolumab

Trial Overview The study tests BMS-986253 in combination with Nivolumab or both Nivolumab and Ipilimumab against cancer. Participants will receive either the experimental medication plus standard treatments or a placebo alongside standard treatments to compare effectiveness.

How Is the Trial Designed?

Group I: Part 2A: BMS-986253 + nivolumab + ipilimumab Experimental Treatment 3 Interventions

Group II: Part 1C: BMS-986253 + nivolumab + ipilimumab Experimental Treatment 3 Interventions

Group III: Part 1B: BMS-986253 + nivolumab Experimental Treatment 2 Interventions

Group IV: Part 1A: BMS-986253 + nivolumab Experimental Treatment 2 Interventions

Group V: Part 2B: Placebo + nivolumab + ipilimumab Placebo Group 3 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

Published Research Related to This Trial

Nivolumab (Opdivo) combined with ipilimumab (Yervoy) has been approved by the FDA as a first-line treatment for adults with unresectable malignant pleural mesothelioma, based on promising results from the CHECKMATE 743 trial.

The approval was supported by an interim analysis comparing the combination therapy to standard chemotherapy, indicating that this new treatment option may offer better outcomes for patients with this challenging cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approves Nivolumab Plus Ipilimumab for Previously Untreated Unresectable Malignant Pleural Mesothelioma. Wright, K.[2021]

Ipilimumab is an immunotherapy that works by inhibiting CTLA-4, leading to enhanced immune system activation, which can effectively treat advanced melanoma and other cancers.

Common side effects of ipilimumab are mostly mild to moderate (grade I or II) and include immune-mediated reactions like inflammatory diarrhea and pruritus, but serious side effects can be managed effectively with corticosteroids or other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab for advanced melanoma: a nursing perspective. Ledezma, B.[2017]

In a study analyzing 2,088 individual case safety reports (ICSRs) related to immune checkpoint inhibitors (ICIs) in Italy, 801 reports documented serious immune-related adverse drug reactions (irADRs), primarily affecting male patients with gastrointestinal and skin toxicities.

Among the ICIs, nivolumab and pembrolizumab were most frequently associated with irADRs, with significant risks identified for pembrolizumab and ipilimumab, highlighting the need for oncologists to recognize and manage these serious side effects effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Inhibitors and Immune-Related Adverse Drug Reactions: Data From Italian Pharmacovigilance Database. Ruggiero, R., Fraenza, F., Scavone, C., 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]

In a review of 129 oncology patients treated with immune checkpoint inhibitors, 51.9% experienced at least one immune-related adverse event (irAE), highlighting the common occurrence of these side effects.

Nearly half of the irAEs were managed according to established guidelines, but there was significant variability in documentation and management practices, indicating a need for improved adherence as immunotherapy use increases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Adherence to Toxicity Management Guidelines for Immune-Related Adverse Events. Teimouri, A., Minard, LV., Scott, SN., et al.[2022]

Nivolumab (Opdivo) significantly improves overall survival and response rates in previously-treated patients with advanced nonsquamous non-small cell lung cancer (NSCLC) compared to docetaxel, as shown in the CheckMate 057 trial.

Nivolumab has a manageable adverse event profile and is better tolerated than docetaxel, making it a valuable treatment option for patients who have progressed after chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: A Review in Advanced Nonsquamous Non-Small Cell Lung Cancer. Keating, GM.[2018]

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]

A review of 2217 adverse drug reaction reports related to immune checkpoint inhibitors (ICIs) from 2011 to 2018 revealed that these drugs, particularly nivolumab, are associated with a higher frequency of serious immune-related adverse events, including gastrointestinal and respiratory disorders.

Emerging safety signals, such as ischaemic heart disease and cardiac failure, were identified, indicating the need for further investigation into the long-term safety profile of ICIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of immune checkpoint inhibitors: An analysis of the Italian spontaneous reporting system database. Cutroneo, PM., Isgrò, V., Ientile, V., et al.[2021]

In the phase III CheckMate 743 study, nivolumab plus ipilimumab significantly improved overall survival in patients with unresectable malignant pleural mesothelioma, with a median overall survival of 18.1 months compared to 14.1 months for chemotherapy, and 3-year overall survival rates of 23% versus 15%.

The combination treatment also showed a manageable safety profile, with no new safety signals reported, and even patients who discontinued due to treatment-related adverse events had a median overall survival of 25.4 months, indicating sustained benefits from the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line nivolumab plus ipilimumab versus chemotherapy in patients with unresectable malignant pleural mesothelioma: 3-year outcomes from CheckMate 743. Peters, S., Scherpereel, A., Cornelissen, R., et al.[2022]

Nivolumab plus ipilimumab showed durable and long-term efficacy in treating advanced non-small cell lung cancer (NSCLC) compared to chemotherapy, regardless of tumor PD-L1 expression levels.

These findings are based on updated results from part 1 of the phase 3 CheckMate 227 trial, indicating that this combination therapy could be a more effective frontline treatment option for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab/Ipilimumab Combo Yields Durable Efficacy in Advanced NSCLC. Kahl, KL.[2021]

After a median follow-up of nearly 55 months, the combination of nivolumab and ipilimumab significantly improved overall survival in patients with advanced non-small cell lung cancer (NSCLC) compared to chemotherapy, with 4-year survival rates of 29% for PD-L1 ≥1% and 24% for PD-L1 <1%.

The safety profile of nivolumab plus ipilimumab remained consistent with previous studies, with immune-mediated adverse events typically occurring early in treatment and resolving quickly, indicating that discontinuation due to these events did not negatively affect long-term survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Nivolumab Plus Ipilimumab in Advanced NSCLC: 4-Year Outcomes From the Randomized, Open-Label, Phase 3 CheckMate 227 Part 1 Trial. Paz-Ares, LG., Ramalingam, SS., Ciuleanu, TE., et al.[2022]

Ipilimumab, an anti-CTLA-4 antibody, has been shown to improve survival in patients with unresectable or metastatic melanoma, with a standard dosing of 3 mg/kg every 3 weeks for a total of 4 doses.

While ipilimumab can cause immune-related adverse events in 15% of patients, most are mild and manageable; however, high-grade events can be serious and require careful monitoring and treatment with corticosteroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab for advanced melanoma: a pharmacologic perspective. Trinh, VA., Hagen, B.[2021]

Citations

1. esmoiotech.org esmoiotech.org/article/S2590-0188(22)00242-8/fulltext

200MO Anti–IL-8 BMS-986253 + nivolumab (NIVO) ± ... We present updated results from part 1 of the phase 1/2 trial of BMS-986253 + NIVO ± IPI in pts with advanced cancer (NCT03400332). Methods. Pts with ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03400332

NCT03400332 | A Study of BMS-986253 in Combination ... The purpose of this study is to investigate experimental medication BMS-986253 in combination with Nivolumab or Nivolumab plus Ipilimumab in participants with ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2018.36.15_suppl.TPS3109

Phase 1b/2 study of nivolumab in combination with an anti ... Here we describe a phase 1b/2 study of the combination of BMS-986253 plus nivolumab in a biomarker-enriched population of pts with advanced ...

4. onclive.com onclive.com/view/bms-986253-plus-nivolumab-ipilimumab-fails-to-boost-responses-in-advanced-melanoma-after-prior-anti-pd--l-1-therapy

BMS-986253 Plus Nivolumab/Ipilimumab Fails to Boost ... BMS-986253 addition to nivolumab and ipilimumab did not improve response rates or progression-free survival in advanced melanoma patients post ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6729083/

Phase I trial of HuMax-IL8 (BMS-986253), an anti-IL-8 ... Preclinical studies have shown that IL-8 blockade may reduce mesenchymal features in tumor cells, making them less resistant to treatment.