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

(CheckMate-1533 Trial)

Recruiting at 81 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for individuals with advanced non-small cell lung cancer (NSCLC) that has spread or recurred. The study examines the effectiveness of two different doses of Nivolumab (an immune therapy) combined with Ipilimumab (another immune therapy) and chemotherapy. Individuals diagnosed with stage IV or recurrent NSCLC who have not received systemic anti-cancer treatments for advanced disease may be suitable candidates. The trial seeks to determine if this combination can better combat cancer compared to existing treatments. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to the development of potentially more effective cancer therapies.

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.

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

Research has shown that combining the drugs nivolumab and ipilimumab with chemotherapy for non-small cell lung cancer (NSCLC) has shown promise in past studies. Patients who received this treatment had a 37% chance of living for five years, even if they discontinued due to side effects. However, some side effects were serious enough to require stopping the treatment.

These results suggest that while the treatment can be effective, it may also cause significant side effects. Although this treatment has been tested before, the current trial continues to gather more information about its safety. Prospective participants should discuss the potential benefits and risks with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Nivolumab, Ipilimumab, and chemotherapy for treating non-small cell lung cancer because it introduces a powerful duo of immunotherapy drugs that enhance the body's own immune response against cancer cells. Unlike standard treatments that primarily rely on chemotherapy alone, this combination leverages immune checkpoint inhibitors (Nivolumab and Ipilimumab), which work by blocking the proteins that prevent immune cells from attacking cancer. This approach not only aims to boost the effectiveness of chemotherapy but also has the potential to provide longer-lasting cancer control by enabling the immune system to recognize and fight the cancer more effectively.

What evidence suggests that this trial's treatments could be effective for Non-Small Cell Lung Cancer?

This trial will evaluate the combination of nivolumab and ipilimumab with chemotherapy for treating non-small cell lung cancer (NSCLC). Research has shown that using nivolumab and ipilimumab together with chemotherapy may help treat NSCLC. In one study, patients who received this combination lived for a median of 17.1 months, compared to 13.9 months for those who did not. After five years, the treatment was effective for 19% of patients using the combination, while it was effective for only 8% of those using chemotherapy alone. Additionally, the five-year survival rate for patients with this combination exceeded the usual 7% for advanced NSCLC. These results suggest that this drug combination might be more effective than chemotherapy alone. ^{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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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]

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 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 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 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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36223558/

Five-Year Survival Outcomes With Nivolumab Plus Ipilimumab ... These data support nivolumab plus ipilimumab as an effective first-line treatment for patients with metastatic non-small-cell lung cancer.

2. esmoopen.com esmoopen.com/article/S2059-7029(25)00992-5/fulltext

final, 6-year outcomes from CheckMate 9LA The 6-year DOR rate was 19% with nivolumab plus ipilimumab with chemotherapy; all patients in the chemotherapy arm were censored or stopped ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1910231

Nivolumab plus Ipilimumab in Advanced Non–Small-Cell ... Among all the patients in the trial, the median duration of overall survival was 17.1 months (95% CI, 15.2 to 19.9) with nivolumab plus ipilimumab and 13.9 ...

4. ejcancer.com ejcancer.com/article/S0959-8049(24)00952-3/fulltext

Five-year outcomes with first-line nivolumab plus ... Five-year duration of response (DOR) rates were 19% versus 8% with nivolumab plus ipilimumab with chemotherapy versus chemotherapy, with ...

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

Five-Year Survival Outcomes With Nivolumab Plus ... Patients with metastatic non–small-cell lung cancer (mNSCLC) have historically had a poor prognosis, with a 5-year survival rate of 7%.