Combination Immunotherapy for Small Cell Lung Cancer

Overseen By Anne Chiang, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Yale University

Must not be taking: Immunosuppressants, Anti-CTLA4

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 2

Duration: Up to 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two immunotherapy drugs, nivolumab and ipilimumab, to evaluate their effects on the immune system and their potential to treat small cell lung cancer (SCLC) that has recurred after previous treatment. The trial targets patients previously treated with platinum-based chemotherapy whose cancer has progressed. Individuals with extensive stage SCLC, who have at least one tumor suitable for biopsy and are not currently on high-dose steroids, may be suitable candidates for this trial. As a Phase 2 trial, this research aims to measure the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant findings.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the drugs nivolumab and ipilimumab are generally safe for people with small cell lung cancer (SCLC). A study found that using these drugs alone or together did not reveal any new safety issues for treating SCLC, making the treatment safe and manageable for patients. These drugs have also been used safely for other types of lung cancer, such as non-small cell lung cancer (NSCLC). While side effects can occur, they are similar to those seen with other treatments that boost the immune system. Patients should always discuss potential risks and benefits with their doctor before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for small cell lung cancer?

Researchers are excited about the combination of Ipilimumab and Nivolumab for small cell lung cancer because these immunotherapy drugs work by enhancing the body's own immune system to fight cancer cells. Unlike traditional chemotherapy, which directly kills cancer cells but can also damage healthy cells, this combo boosts the immune response specifically against cancer. Ipilimumab and Nivolumab target specific proteins on immune cells, removing the brakes and allowing the immune system to attack the cancer more effectively. This approach could lead to more durable responses and fewer side effects compared to conventional treatments.

What evidence suggests that this treatment might be an effective treatment for small cell lung cancer?

Research has shown that using nivolumab and ipilimumab together can be promising for treating various types of cancer. Studies have found that this combination can extend patients' lives compared to traditional chemotherapy. In individuals with advanced non-small cell lung cancer (NSCLC), this treatment has resulted in longer survival times. In this trial, participants with small cell lung cancer (SCLC) will receive the combination of nivolumab and ipilimumab, which shows potential because both types of lung cancer often respond to similar treatments. Early results suggest that the benefits of this combination endure over time. ^{4 6 7 8 9}

Who Is on the Research Team?

Anne Chiang, MD, PhD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

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 have brain metastases but am not on high-dose steroids and finished radiation at least 2 weeks ago.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab and Nivolumab

Trial Overview The 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.

How Is the Trial Designed?

Group I: Nivolumab and Ipilimumab Experimental Treatment 1 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.

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

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

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 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]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

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 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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Inhibitors and Immune-Related Adverse Drug Reactions: Data From Italian Pharmacovigilance Database. Ruggiero, R., Fraenza, F., Scavone, C., 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]

In a study of 1255 patients with metastatic non-small cell lung cancer (NSCLC), first-line treatment with nivolumab plus ipilimumab (NIVO+IPI) showed a high incidence of treatment-related adverse events (TRAEs), with 78% experiencing any-grade TRAEs and 34% experiencing severe (grade 3 or 4) TRAEs, but the treatment was generally well tolerated.

Patients who discontinued NIVO+IPI due to TRAEs still had a favorable long-term survival rate, with a 3-year overall survival of 50%, indicating that stopping treatment because of side effects did not negatively impact their long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC: A Pooled Analysis of CheckMate 227, CheckMate 568, and CheckMate 817. Paz-Ares, LG., Ciuleanu, TE., Pluzanski, A., et al.[2023]

A review of 2217 adverse drug reaction reports related to immune checkpoint inhibitors (ICIs) from 2011 to 2018 revealed that these drugs, particularly nivolumab, are associated with a higher frequency of serious immune-related adverse events, including gastrointestinal and respiratory disorders.

Emerging safety signals, such as ischaemic heart disease and cardiac failure, were identified, indicating the need for further investigation into the long-term safety profile of ICIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of immune checkpoint inhibitors: An analysis of the Italian spontaneous reporting system database. Cutroneo, PM., Isgrò, V., Ientile, V., et al.[2021]

Citations

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

Five-Year Survival Outcomes With Nivolumab Plus Ipilimumab ... Nivolumab plus ipilimumab increased 5-year survivorship versus chemotherapy, including long-term, durable clinical benefit regardless of tumor PD-L1 expression.

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

Nivolumab plus Ipilimumab in Advanced Non–Small-Cell ... First-line treatment with nivolumab plus ipilimumab resulted in a longer duration of overall survival than did chemotherapy in patients with NSCLC.

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

final, 6-year outcomes from CheckMate 9LA The phase III CheckMate 9LA study demonstrated durable overall survival (OS) benefit with nivolumab plus ipilimumab with chemotherapy versus ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1525730425000099

Comparative Effectiveness of Nivolumab and Ipilimumab ... This study aimed to compare the treatment response and real-world outcomes of NIC with the current standard of care pembrolizumab plus chemotherapy (PC) in PD- ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39369790/

Long-Term Survival Outcomes With First-Line Nivolumab ... Nivolumab plus ipilimumab with or without chemotherapy provides a long-term, durable clinical benefit in patients with metastatic NSCLC and tumor PD-L1 lower ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38240151/

Real-world safety of first-line immuno-oncology ... These results show that in a real-world setting, NIVO + IPI-based regimens have similar safety to other IO + chemotherapy combinations when used as a first ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03048136

NCT03048136 | A Safety Study of Nivolumab in ... 1) Stage IV or recurrent non-Small cell lung cancer; 2) Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1; 3) Prior adjuvant or neoadjuvant ...

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

Five-Year Survival: Nivolumab/Ipilimumab vs Chemo for NSCLC Patients with metastatic non–small-cell lung cancer (mNSCLC) have historically had a poor prognosis, with a 5-year survival rate of 7%.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT02046733

Study Details | NCT02046733 | Small Cell Lung Carcinoma ... Both, nivolumab monotherapy and nivolumab plus ipilimumab combination treatment were tolerable for the treatment of SCLC, and no new safety profile was ...