Nivolumab + CCR2/5-inhibitor/Anti-IL-8 for Lung Cancer

Overseen By Thomas Marron, MD PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Icahn School of Medicine at Mount Sinai

Must not be taking: Investigational agents, Immunosuppressants

Disqualifiers: Metastatic disease, Autoimmune, HIV, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine whether combining nivolumab (Opdivo) with other medications before and after surgery can enhance the immune response against lung cancer and improve long-term survival. Different treatment groups will test nivolumab alone or with other experimental drugs, such as BMS-813160 (a CCR2/5-inhibitor) and BMS-986253 (an Anti-IL-8). Individuals diagnosed with non-small cell lung cancer (NSCLC) or hepatocellular carcinoma (HCC) who are potential candidates for tumor surgery may be eligible to participate. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or any form of immunosuppressive therapy, you must stop at least 7 days before participating.

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

Research shows that the combination of nivolumab and BMS-813160 is generally safe for patients. Previous studies found that this combination does not cause any unexpected side effects. Most side effects were mild, such as fatigue and nausea.

Similarly, the combination of nivolumab and BMS-986253 has undergone safety testing. Early studies indicate that it is also well-tolerated. Common side effects included fatigue and skin reactions, but these were usually easy to manage.

Nivolumab itself is already approved by the FDA for treating certain types of lung cancer, indicating that its safety is well-understood. While combining it with other drugs remains under study, current evidence is reassuring. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they aim to tackle lung cancer in innovative ways. Unlike standard treatments like chemotherapy, Nivolumab is an immunotherapy that boosts the body's own immune system to fight cancer cells. The addition of BMS-813160, a CCR2/5-inhibitor, potentially blocks certain pathways that tumors use to grow and spread, adding a new layer of attack. Meanwhile, BMS-986253 targets IL-8, a molecule that helps tumors evade the immune system, offering another unique approach. This combination of targeting multiple mechanisms could lead to more effective and comprehensive treatment options for lung cancer patients.

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

Research has shown that nivolumab, a type of immunotherapy, may help treat non-small cell lung cancer (NSCLC). Studies have found that it can increase survival rates for patients with this cancer. In this trial, some participants will receive nivolumab with BMS-813160, a drug that blocks certain proteins. Early results suggest this combination might strengthen the immune system's attack on tumors. Other participants will receive nivolumab combined with BMS-986253, which targets inflammation related to cancer. This combination has shown promise in improving patient outcomes. Both combinations aim to enhance the body's natural ability to fight cancer, offering hope for better long-term survival. ^{1 6 7 8 9}

Who Is on the Research Team?

Thomas Marron, MD PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

This trial is for adults with operable lung or liver cancer (NSCLC or HCC) who have functioning organs and marrow. They must agree to use birth control, provide blood samples, undergo leukapheresis at specified locations, and have biopsies. Excluded are those on other trials, with uncontrolled illness, recent chemo/radiotherapy for another tumor, metastatic disease not curable by surgery, pregnant/nursing women, certain immune conditions including active autoimmune diseases treated within a year or current immunosuppressives.

Inclusion Criteria

I have been diagnosed with non-small cell lung cancer or liver cancer.

My organs and bone marrow are working well.

I am willing to have a leukapheresis procedure at Mount Sinai Hospital or New York Blood Bank.

Exclusion Criteria

You have had an allergic reaction to any protein-based treatments in the past.

I have been treated for an autoimmune disease in the last year.

I have active Hepatitis B.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive nivolumab with either CCR2/5-inhibitor or anti-IL-8 before surgery

8 weeks

2 visits (in-person) for nivolumab dosing

Surgery

Surgical resection of the tumor is performed

1 week

1 visit (in-person)

Adjuvant Treatment

Participants receive additional doses of nivolumab following recovery from surgery

12 weeks

3 visits (in-person) for nivolumab dosing

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• BMS-813160
• BMS-986253
• Nivolumab

Trial Overview The study tests the effect of Nivolumab combined with either CCR2/5-inhibitor (BMS-813160) or anti-IL-8 (BMS-986253) before and after surgery in NSCLC/HCC patients. It aims to see if these drugs boost immune response against tumors seen during surgery and improve survival rates.

How Is the Trial Designed?

Group I: Cohort E Experimental Treatment 2 Interventions

HCC: Nivolumab + BMS-986253

Group II: Cohort D Experimental Treatment 2 Interventions

HCC: Nivolumab + BMS-813160

Group III: Cohort C Experimental Treatment 1 Intervention

HCC: Nivolumab

Group IV: Cohort B Experimental Treatment 2 Interventions

NSCLC: Nivolumab + BMS-986253

Group V: Cohort A Experimental Treatment 2 Interventions

NSCLC: Nivolumab + BMS-813160

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Bristol-Myers Squibb

Industry 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 immune checkpoint inhibitor, showed a tolerable safety profile in 52 patients with advanced non-small-cell lung cancer (NSCLC), with 71% experiencing treatment-related adverse events, primarily fatigue and rash.

The treatment resulted in a confirmed objective response rate of 23%, with some patients achieving ongoing complete responses, and a median overall survival of 19.4 months, indicating its potential as an effective first-line therapy for advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Monotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer. Gettinger, S., Rizvi, NA., Chow, LQ., et al.[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]

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 is the first approved PD-1 inhibitor that helps the immune system fight against tumors, specifically for patients with unresectable melanoma.

Early phase studies have shown promising results for nivolumab in treating solid tumors like non-small cell lung cancer (NSCLC), especially when combined with chemotherapy and other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab in NSCLC: latest evidence and clinical potential. Sundar, R., Cho, BC., Brahmer, JR., et al.[2022]

In a phase III trial, nivolumab significantly improved health-related quality of life (HRQoL) and disease-related symptoms compared to docetaxel in patients with advanced non-squamous non-small cell lung cancer, with improvements noted at multiple time points (weeks 12, 24, 30, and 42).

Patients receiving nivolumab experienced a longer time to first deterioration in HRQoL compared to those treated with docetaxel, indicating a more favorable safety profile and sustained symptom relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of health-related quality of life and symptoms in patients with advanced non-squamous non-small cell lung cancer treated with nivolumab or docetaxel in CheckMate 057. Reck, M., Brahmer, J., Bennett, B., et al.[2019]

In the Asian subpopulation with advanced non-small cell lung cancer (NSCLC) and PD-L1 expression ≥1%, patients treated with nivolumab plus ipilimumab showed significantly improved overall survival (OS) and progression-free survival (PFS) compared to those receiving chemotherapy, with a 3-year OS rate of 53% versus 37%.

The safety profile of nivolumab plus ipilimumab was manageable, with grade 3-4 treatment-related adverse events occurring in 40% of patients, similar to the 36% in the chemotherapy group, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. O'Byrne, KJ., Lee, KH., Kim, SW., et al.[2022]

Immune checkpoint inhibitors, such as ipilimumab and anti-PD-1 agents like nivolumab and pembrolizumab, work by enhancing the immune system's ability to fight non-small cell lung cancer (NSCLC), differing from traditional chemotherapy that targets tumor cells directly.

Preliminary evidence indicates that these inhibitors can be effective as standalone treatments or in combination with chemotherapy, highlighting their potential in improving outcomes for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging immunotherapies in the treatment of non-small cell lung cancer (NSCLC): the role of immune checkpoint inhibitors. Langer, CJ.[2020]

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 is a PD-1 immune checkpoint inhibitor that effectively enhances antitumor immunity by blocking the PD-1 receptor on activated T cells, which helps reverse immune suppression in cancer patients.

Clinical trials have demonstrated the efficacy of nivolumab in treating various cancers, including non-small-cell lung cancer, melanoma, and renal cell carcinoma, making it a promising option in targeted immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab as Programmed Death-1 (PD-1) Inhibitor for Targeted Immunotherapy in Tumor. Guo, L., Zhang, H., Chen, B.[2022]

Citations

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Non-Small Cell Lung Cancer (NSCLC) Treatment OPDIVO® (nivolumab) alone, or with YERVOY® (ipilimumab) can be used as an immunotherapy treatment option for adults with certain types of NSCLC.