25 Participants Needed

Combination Immunotherapy for Small Cell Lung Cancer

KP
AC
Overseen ByAnne Chiang, MD, PhD
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

What is the purpose of this trial?

This is a pilot study of patients who previously received platinum chemotherapy with recurrent SCLC to evaluate the change in the ratio of intratumoral Teff/Treg cells and clinical benefit of treatment with nivolumab and ipilimumab.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as systemic immunosuppressive drugs and high-dose steroids, at least 2 weeks before starting the study. However, inhaled or topical steroids and standard-dose NSAIDs are allowed. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drugs Ipilimumab and Nivolumab for small cell lung cancer?

Research shows that immune checkpoint inhibitors, like Ipilimumab and Nivolumab, have shown promise in treating small cell lung cancer (SCLC) by improving survival when combined with chemotherapy. Although specific data for these drugs in SCLC is still being studied, similar treatments have shown benefits in other cancers, suggesting potential effectiveness.12345

Is the combination of Ipilimumab and Nivolumab generally safe for humans?

The combination of Ipilimumab and Nivolumab has been associated with increased risk of immune-related side effects, which are reactions where the immune system attacks normal cells in the body. These side effects have been observed in treatments for conditions like melanoma and non-small cell lung cancer, and more studies are needed to fully understand their safety.678910

How is the drug combination of Ipilimumab and Nivolumab unique for treating small cell lung cancer?

The combination of Ipilimumab and Nivolumab is unique for treating small cell lung cancer because it uses two drugs that work together to boost the immune system's ability to fight cancer, offering a new option for patients who have limited treatments after chemotherapy fails.29111213

Research Team

AC

Anne Chiang, MD, PhD

Principal Investigator

Yale University

Eligibility Criteria

This trial is for patients with recurrent extensive stage small cell lung cancer (SCLC) after platinum-based chemotherapy. Eligible participants may have treated brain metastases, an ECOG performance status of 0 to 2, and measurable disease. Excluded are those with HIV/HBV/HCV, recent major surgery or trauma, pregnant or lactating women, active autoimmune diseases requiring treatment in the past 3 months, untreated symptomatic CNS metastases, and recent other treatments.

Inclusion Criteria

I have a tumor that can be biopsied.
I have extensive stage small cell lung cancer that got worse after treatment, including platinum-based therapy.
I can take care of myself and am up and about more than half of my waking hours.
See 1 more

Exclusion Criteria

I have not taken high doses of steroids or immunosuppressants for an autoimmune disease in the last 3 months.
I have lung disease that causes symptoms or could affect lung-related side effects from treatment.
I have not had major surgery or a serious injury in the last 4 weeks.
See 7 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive combination therapy with nivolumab and ipilimumab, starting with 4 doses of each, followed by nivolumab every 2 weeks until progression or unacceptable toxicity

Up to 24 months
Every 2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of response rate, progression-free survival, and changes in tumor microenvironment

Up to 24 months

Treatment Details

Interventions

  • Ipilimumab and Nivolumab
Trial OverviewThe study tests a combination immunotherapy using Ipilimumab and Nivolumab on SCLC patients who've had disease progression post-platinum therapy. It aims to assess changes in tumor immune cells ratio and clinical benefits from the treatment.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Nivolumab and IpilimumabExperimental Treatment1 Intervention
Patients will be treated with nivolumab 1 mg/kg and ipilimumab 3 mg/kg, starting on Day 1. Patients will receive 4 doses of each nivolumab and ipilimumab and then will receive nivolumab 240 mg starting week 13 (day 85) every 2 weeks until progression, unacceptable toxicity, withdrawal of consent, or the study ends, whichever occurs first.

Find a Clinic Near You

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials
1,963
Recruited
3,046,000+

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 profile image

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 profile image

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

Combining immune checkpoint inhibitors (ICIs) like anti-PD-1/PD-L1 with chemotherapy significantly improves overall survival and progression-free survival in small cell lung cancer patients, with hazard ratios of 0.83 and 0.80, respectively, based on a review of five studies.
The combination treatment does not increase the rate of severe adverse events compared to conventional chemotherapy, indicating that it is a tolerable option for patients.
Meta-analysis of the Efficacy and Tolerability of Immune Checkpoint Inhibitors Combined With Chemotherapy in First-line Treatment of Small Cell Lung Cancer.Wu, J., Zhang, A., Li, L., 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.
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 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.
Immune Checkpoint Inhibitors and Immune-Related Adverse Drug Reactions: Data From Italian Pharmacovigilance Database.Ruggiero, R., Fraenza, F., Scavone, C., et al.[2022]

References

The evolving landscape of immunotherapy in small-cell lung cancer: A focus on predictive biomarkers. [2019]
Second-line nivolumab in relapsed small-cell lung cancer: CheckMate 331☆. [2022]
Meta-analysis of the Efficacy and Tolerability of Immune Checkpoint Inhibitors Combined With Chemotherapy in First-line Treatment of Small Cell Lung Cancer. [2021]
Immunomodifiers in combination with conventional chemotherapy in small cell lung cancer: a phase II, randomized study. [2021]
First-line immune checkpoint inhibitors for extensive stage small-cell lung cancer: clinical developments and future directions. [2023]
Retrospective Side Effect Profiling of the Metastatic Melanoma Combination Therapy Ipilimumab-Nivolumab Using Adverse Event Data. [2022]
Immune Checkpoint Inhibitors and Immune-Related Adverse Drug Reactions: Data From Italian Pharmacovigilance Database. [2022]
Safety of First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC: A Pooled Analysis of CheckMate 227, CheckMate 568, and CheckMate 817. [2023]
First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. [2022]
Safety profile of immune checkpoint inhibitors: An analysis of the Italian spontaneous reporting system database. [2021]
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]
Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. [2022]
Long-term survival with first-line nivolumab plus ipilimumab in patients with advanced non-small-cell lung cancer: a pooled analysis. [2023]