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

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

48 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Nivolumab for lung cancer?

Nivolumab has shown to significantly improve overall survival and progression-free survival in patients with advanced non-small cell lung cancer (NSCLC) compared to the chemotherapy drug docetaxel, as demonstrated in several clinical trials. ^{1 2 3 4 5}

Is the combination of Nivolumab and other inhibitors safe for humans?

Nivolumab, used in treating advanced lung cancer, has shown a favorable safety profile in several studies, meaning it is generally well-tolerated by patients. It has been associated with manageable side effects compared to other treatments like docetaxel. ^{2 4 6 7 8}

How is the drug Nivolumab + CCR2/5-inhibitor/Anti-IL-8 different from other lung cancer treatments?

This treatment combines Nivolumab, a PD-1 inhibitor that helps the immune system attack cancer cells, with a CCR2/5-inhibitor and Anti-IL-8, which may target inflammation and immune cell movement. This combination aims to enhance the immune response against lung cancer, potentially offering a novel approach compared to standard treatments that typically focus on chemotherapy or single-agent immunotherapy. ^{2 3 9 10 11}

What is the purpose of this trial?

The purpose of this research study is to study the effect of giving nivolumab with CCR2/5-inhibitor or anti-IL-8 before surgery, and after surgery, with the goal of determining if this medicine results in: 1. A significant immune response against their tumor (which the study team will see in the tumor that is taken out at the time of surgery) 2. Improvement in long term survival rates

Research Team

Thomas Marron, MD PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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]

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]

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]

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]

References

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

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

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

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

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Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer. [2022]

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

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Nivolumab Monotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer. [2022]

6. England 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. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitors in lung cancer: past, present and future. [2017]

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

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. [2022]

9. England pubmed.ncbi.nlm.nih.gov

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

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Nivolumab as Programmed Death-1 (PD-1) Inhibitor for Targeted Immunotherapy in Tumor. [2022]

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Nivolumab in NSCLC: latest evidence and clinical potential. [2022]