Nivolumab + Ipilimumab + Chemotherapy for Non-Small Cell Lung Cancer

(CheckMate-1533 Trial)

Recruiting at 47 trial locations

Overseen By BMS Clinical Trials Contact Center www.BMSClinicalTrials.com

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Bristol-Myers Squibb

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Autoimmune disease, CNS metastases, 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: Unknown

Duration: 12 weeks

76 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on certain treatments like corticosteroids above a specific dose or other immunosuppressive medications shortly before joining the trial.

What data supports the effectiveness of the drug combination Nivolumab, Ipilimumab, and Chemotherapy for Non-Small Cell Lung Cancer?

Research shows that using Nivolumab and Ipilimumab together can help people with advanced non-small cell lung cancer live longer compared to just using chemotherapy. Adding a short course of chemotherapy to this combination might make the treatment even more effective. ^{1 2 3 4 5}

Is the combination of Nivolumab, Ipilimumab, and Chemotherapy safe for humans?

The combination of Nivolumab and Ipilimumab, often used with chemotherapy, has been shown to have a manageable safety profile in patients with non-small cell lung cancer, though it can cause immune-related side effects. These side effects are common and can be serious, but they are often associated with better treatment outcomes. ^{2 6 7 8 9}

What makes the drug combination of Nivolumab, Ipilimumab, and Chemotherapy unique for treating non-small cell lung cancer?

This drug combination is unique because it combines immunotherapy (Nivolumab and Ipilimumab) with chemotherapy, which has been shown to improve survival rates in patients with advanced non-small cell lung cancer compared to chemotherapy alone. The immunotherapy drugs help the immune system recognize and attack cancer cells, offering a novel approach compared to traditional treatments. ^{1 2 10 11 12}

What is the purpose of this trial?

The purpose of this study is to evaluate two dosing regimens of subcutaneous Nivolumab in combination with intravenous Ipilimumab and chemotherapy in participants with previously untreated metastatic or recurrent Non-Small Cell Lung Cancer (NSCLC)

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This trial is for individuals with previously untreated metastatic or recurrent Non-Small Cell Lung Cancer (NSCLC). Specific eligibility criteria are not provided, but typically participants must meet certain health standards and may be required to have a particular stage or subtype of NSCLC.

Inclusion Criteria

My cancer can be measured on scans and was checked within the last 28 days.

I haven't received any systemic anti-cancer treatments for advanced or metastatic disease.

I finished chemotherapy for early-stage lung cancer more than 6 months ago.

Exclusion Criteria

My cancer does not have mutations treatable with targeted therapy.

I do not have any autoimmune diseases.

I had cancer before, but it has been in complete remission for at least 2 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive subcutaneous Nivolumab in combination with intravenous Ipilimumab and chemotherapy

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Treatment Details

Interventions

• Carboplatin
• Cisplatin
• Ipilimumab
• Nivolumab
• Paclitaxel
• Pemetrexed

Trial Overview The study is testing two different dosing schedules of Nivolumab given under the skin, combined with Ipilimumab given through IV and chemotherapy drugs. The goal is to see which regimen works better for treating NSCLC.

Participant Groups

Group I: Arm B Experimental Treatment 6 Interventions

Group II: Arm A Experimental Treatment 6 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

Findings from Research

In a pooled analysis of 1332 patients with advanced non-small-cell lung cancer (NSCLC), the combination of nivolumab and ipilimumab showed a median overall survival (OS) of 18.6 months and a 3-year OS rate of 35%, indicating significant long-term survival benefits compared to traditional chemotherapy.

The study found that patients who responded to treatment at 6 months had markedly better survival rates, with a 3-year OS of 66% for responders, highlighting the importance of early response in predicting long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival with first-line nivolumab plus ipilimumab in patients with advanced non-small-cell lung cancer: a pooled analysis. Borghaei, H., Ciuleanu, TE., Lee, JS., et al.[2023]

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]

In patients with non-small cell lung cancer (NSCLC), platinum-based chemotherapy significantly increased the presence of NSCLC-specific antibodies and various immune markers in the blood, indicating an immune response to the treatment.

Immune checkpoint inhibitors (ICIs) like Nivolumab and Pembrolizumab also altered the immune profile, enhancing certain T-cell and B-cell markers, which suggests that both chemotherapy and ICIs can modify the immune landscape in advanced NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-cell mass cytometric analysis of peripheral immunity and multiplex plasma marker profiling of non-small cell lung cancer patients receiving PD-1 targeting immune checkpoint inhibitors in comparison with platinum-based chemotherapy. Neuperger, P., Szalontai, K., Gémes, N., et al.[2023]

In a phase 3 trial involving 1150 patients with advanced non-small-cell lung cancer (NSCLC), the combination of nivolumab and ipilimumab with two cycles of chemotherapy significantly improved overall survival compared to chemotherapy alone, with a median survival of 15.6 months versus 10.9 months.

The treatment regimen showed a favorable safety profile, with serious treatment-related adverse events occurring in 30% of the experimental group compared to 18% in the control group, indicating that the benefits of the combination therapy outweigh the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial. Paz-Ares, L., Ciuleanu, TE., Cobo, M., et al.[2021]

In a study of patients with non-small cell lung cancer treated with nivolumab, those who experienced serious adverse events (grade ≥3) had significantly better overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) compared to those without such events.

The findings suggest that while serious adverse events are typically concerning, they may be associated with a more favorable treatment response in patients receiving nivolumab, indicating a complex relationship between adverse effects and treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious Immune-related Adverse Events Are Associated With Greater Efficacy of Nivolumab Therapy Against Non-small Cell Lung Cancer. Blazek, J., Hosek, P., Hrabcova, K., et al.[2023]

In a study of 311 patients treated with nivolumab or pembrolizumab for advanced melanoma or lung cancer, 37.3% experienced immune-related adverse events, which were linked to improved overall survival rates.

Patients who had immune-related adverse events showed a significantly higher overall response rate (53.9%) compared to those without such events (12.9%), suggesting that these adverse effects may indicate better treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The prognostic impact of immune-related adverse events during anti-PD1 treatment in melanoma and non-small-cell lung cancer: a real-life retrospective study. Dupont, R., Bérard, E., Puisset, F., et al.[2021]

Combining nivolumab and ipilimumab shows improved effectiveness in treating metastatic melanoma compared to using either drug alone, based on a retrospective analysis of approximately 7700 patients.

The combination therapy presents a safety profile that includes immune-related adverse events from both drugs, indicating that while the combination is effective, it also carries a heightened risk of toxicity that needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective Side Effect Profiling of the Metastatic Melanoma Combination Therapy Ipilimumab-Nivolumab Using Adverse Event Data. Soldatos, TG., Dimitrakopoulou-Strauss, A., Larribere, L., et al.[2022]

Nivolumab plus ipilimumab (N+I) and nivolumab plus ipilimumab with chemotherapy (N+I+chemotherapy) improve overall survival and progression-free survival for patients with metastatic non-small cell lung cancer (NSCLC), but both treatments are not cost-effective compared to chemotherapy alone, with high incremental cost-effectiveness ratios (ICERs) of $239,072 and $838,198 per quality-adjusted life year (QALY) respectively.

The cost-effectiveness analysis showed that N+I had a very low probability (2.6%) of being considered cost-effective at a willingness-to-pay threshold of $150,000 per QALY, indicating that while these treatments may improve survival, they come at a significant financial burden to the healthcare system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness of Nivolumab Plus Ipilimumab With and Without Chemotherapy for Advanced Non-Small Cell Lung Cancer. Yang, SC., Kunst, N., Gross, CP., et al.[2022]

In a phase 1 study involving 78 patients with advanced non-small-cell lung cancer (NSCLC), the combination of nivolumab and ipilimumab as first-line therapy demonstrated a tolerable safety profile with no treatment-related deaths and manageable adverse events, such as increased lipase and pneumonitis.

The treatment showed promising efficacy, with confirmed objective response rates of 47% in the ipilimumab every-12-weeks cohort and 38% in the every-6-weeks cohort, suggesting potential benefits over anti-PD-1 monotherapy and warranting further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus ipilimumab as first-line treatment for advanced non-small-cell lung cancer (CheckMate 012): results of an open-label, phase 1, multicohort study. Hellmann, MD., Rizvi, NA., Goldman, JW., et al.[2022]

In a phase 3 clinical trial involving 252 patients with advanced squamous non-small cell lung cancer (NSCLC), the combination of nivolumab and ipilimumab did not significantly improve overall survival compared to nivolumab alone, with median survival times of 10 months and 11 months respectively.

While the combination treatment showed a slightly better progression-free survival (IA-PFS) of 3.8 months compared to 2.9 months for nivolumab alone, the difference was not statistically significant, and both treatments had similar response rates and adverse event profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Plus Ipilimumab vs Nivolumab for Previously Treated Patients With Stage IV Squamous Cell Lung Cancer: The Lung-MAP S1400I Phase 3 Randomized Clinical Trial. Gettinger, SN., Redman, MW., Bazhenova, L., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Long-term survival with first-line nivolumab plus ipilimumab in patients with advanced non-small-cell lung cancer: a pooled analysis. [2023]

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

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

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

Nivolumab plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Single-cell mass cytometric analysis of peripheral immunity and multiplex plasma marker profiling of non-small cell lung cancer patients receiving PD-1 targeting immune checkpoint inhibitors in comparison with platinum-based chemotherapy. [2023]

5. England pubmed.ncbi.nlm.nih.gov

First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial. [2021]

6. Greece pubmed.ncbi.nlm.nih.gov

Serious Immune-related Adverse Events Are Associated With Greater Efficacy of Nivolumab Therapy Against Non-small Cell Lung Cancer. [2023]

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

The prognostic impact of immune-related adverse events during anti-PD1 treatment in melanoma and non-small-cell lung cancer: a real-life retrospective study. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Retrospective Side Effect Profiling of the Metastatic Melanoma Combination Therapy Ipilimumab-Nivolumab Using Adverse Event Data. [2022]

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

Predictive value of immune-related adverse events during pembrolizumab treatment in non-small cell lung cancer. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness of Nivolumab Plus Ipilimumab With and Without Chemotherapy for Advanced Non-Small Cell Lung Cancer. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Nivolumab plus ipilimumab as first-line treatment for advanced non-small-cell lung cancer (CheckMate 012): results of an open-label, phase 1, multicohort study. [2022]

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

Nivolumab Plus Ipilimumab vs Nivolumab for Previously Treated Patients With Stage IV Squamous Cell Lung Cancer: The Lung-MAP S1400I Phase 3 Randomized Clinical Trial. [2022]