Pembrolizumab + Chemotherapy for Small Cell Lung Cancer

Recruiting at 49 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Cardiovascular disease, Autoimmune disease, 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: 4

Duration: 12 weeks

120 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing new drugs combined with existing treatments and chemotherapy to see if they can better treat patients with severe, widespread lung cancer by boosting the immune system and enhancing chemotherapy effects.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the study team or your doctor to understand how your medications might interact with the trial treatments.

What data supports the effectiveness of this drug for small cell lung cancer?

Research shows that pembrolizumab, when combined with chemotherapy drugs like etoposide and platinum compounds, has shown antitumor activity and improved survival in patients with extensive-stage small-cell lung cancer. Additionally, similar combinations with other drugs like durvalumab have also demonstrated significant improvements in overall survival. ^{1 2 3 4 5}

Is the combination of pembrolizumab and chemotherapy safe for humans?

Pembrolizumab, when combined with chemotherapy, has been studied in various cancers and is generally considered safe, though it can cause side effects like fatigue, nausea, and loss of appetite. In combination with lenvatinib, common side effects include high blood pressure, diarrhea, and weight loss. ^{3 6 7 8 9}

What makes the drug pembrolizumab combined with chemotherapy unique for treating small cell lung cancer?

This treatment is unique because it combines pembrolizumab, an immunotherapy drug that helps the immune system attack cancer cells, with chemotherapy drugs like etoposide and platinum compounds, offering a new approach for patients with extensive-stage small-cell lung cancer who have not been treated before. ^{2 3 4 5 6}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for adults with extensive-stage small cell lung cancer who need first-line therapy. They must not be pregnant or breastfeeding, agree to contraception, have good organ function and performance status, and no prior treatments for SCLC. Exclusions include previous immunotherapy, certain heart conditions, uncontrolled diseases, recent major surgery, active infections like HIV/Hepatitis B/C, and other factors that could affect participation.

Inclusion Criteria

I am not pregnant or breastfeeding and meet the birth control requirements.

I am a man willing to use contraception and not donate sperm.

My small cell lung cancer is at stage IV.

Exclusion Criteria

I haven't had a major heart issue or blood clot in the past year.

I have a history of or currently have a neurological disorder related to cancer.

Your heart's electrical activity (QT interval) is longer than normal.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab, investigational agents, and chemotherapy for first-line treatment of ES-SCLC

12 weeks

4 cycles of chemotherapy, each cycle lasting 3 weeks

Maintenance Treatment

Participants continue receiving pembrolizumab and investigational agents until disease progression or discontinuation

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Treatment Details

Interventions

• Boserolimab
• Carboplatin
• Cisplatin
• Etoposide
• Lenvatinib
• MK-4830
• MK-5890
• Pembrolizumab

Trial Overview The study tests new drugs (MK-4830, boserolimab/MK-5890 & lenvatinib/MK-7902) combined with pembrolizumab & chemotherapy in treating ES-SCLC. It's an exploratory trial without formal hypothesis testing to assess the safety and effectiveness of these combinations as a first treatment option.

Participant Groups

Group I: Pembrolizumab + MK-4830 + Chemotherapy Experimental Treatment 5 Interventions

Participants receive pembrolizumab 200 mg IV infusion on Day 1 of each cycle (cycle length = 3 weeks) every 3 weeks (Q3W) up to 35 administrations (up to approximately 2 years) or until disease progression (PD) or discontinuation, MK-4830 800 mg IV infusion on Day 1 of each cycle Q3W, up to 35 administrations (up to approximately 2 years) or until PD or discontinuation; etoposide 100 mg/m\^2 on Days 1, 2, 3 of each cycle for up to 4 cycles (up to approximately 12 weeks) and cisplatin 75 mg/m\^2 or carboplatin AUC 5 mg/ml/min IV, Day 1 of each cycle Q3W up to 4 cycles (up to approximately 12 weeks) or until PD or discontinuation.

Group II: Pembrolizumab + Lenvatinib + Chemotherapy Experimental Treatment 5 Interventions

Participants receive pembrolizumab 200 mg IV infusion on Day 1 of each 3 week cycle (Q3W) up to 35 administrations (up to approximately 2 years) or until PD or discontinuation, lenvatinib 8 mg once daily (QD) orally up to Cycles 1-4 cycles and up to 20 mg QD orally for Cycles 5-31 or until PD or discontinuation; etoposide 100 mg/m\^2 on Days 1, 2, 3 of each cycle for up to 4 cycles (up to approximately 12 weeks) and cisplatin 75 mg/m\^2 or carboplatin AUC 5 mg/ml/min IV, Day 1 of each cycle Q3W up to 4 cycles (up to approximately 12 weeks) or until PD or discontinuation.

Group III: Pembrolizumab + Boserolimab + Chemotherapy Experimental Treatment 5 Interventions

Participants receive pembrolizumab 200 mg IV infusion on Day 1 of each cycle Q3W up to 35 administrations (up to approximately 2 years) or until PD or discontinuation, boserolimab 30 mg IV infusion on Day 1 of each cycle (cycle length = 6 weeks) every 6 weeks (Q6W), up to 18 administrations (up to approximately 2 years) or until PD or discontinuation; etoposide 100 mg/m\^2 on Days 1, 2, 3 of each cycle for up to 4 cycles (up to approximately 12 weeks) and cisplatin 75 mg/m\^2 or carboplatin AUC 5 mg/ml/min IV, Day 1 of each cycle Q3W up to 4 cycles (up to approximately 12 weeks) or until PD or discontinuation.

Boserolimab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as KEYTRUDA for:

• Melanoma
• Non-small cell lung cancer
• Head and neck cancer
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Endometrial carcinoma

Approved in United States as KEYTRUDA for:

• Melanoma
• Non-small cell lung cancer
• Head and neck cancer
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Endometrial carcinoma
• Esophageal carcinoma
• Cervical cancer

Approved in Canada as KEYTRUDA for:

• Melanoma
• Non-small cell lung cancer
• Head and neck cancer
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Endometrial carcinoma

Approved in Japan as KEYTRUDA for:

• Melanoma
• Non-small cell lung cancer
• Head and neck cancer
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma

Who Is Running the Clinical Trial?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

Engineering degree from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

J.D. from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

Combination treatments using platinum compounds and etoposide show median survival rates of 7 to 10 months for extensive-stage and 15 to 20 months for limited-stage small cell lung cancer, indicating their effectiveness in improving patient outcomes.

Adding paclitaxel to platinum/etoposide regimens has shown promising results in early studies, with good activity and manageable toxicity, and ongoing phase III trials aim to clarify its role in enhancing treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The current role and future prospects of paclitaxel in the treatment of small cell lung cancer. Hainsworth, JD., Greco, FA.[2015]

In a real-life study of 121 patients with advanced non-squamous non-small cell lung cancer, the combination of pembrolizumab and chemotherapy resulted in a median progression-free survival of 9 months and overall survival of 20.6 months, demonstrating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with manageable side effects; however, 17.5% of patients experienced grade 3-4 adverse events, and there were two treatment-related deaths, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). Renaud, E., Ricordel, C., Corre, R., et al.[2023]

In the CASPIAN study involving 805 patients with extensive-stage small-cell lung cancer (ES-SCLC), the combination of durvalumab and platinum-etoposide significantly improved overall survival compared to platinum-etoposide alone, with a median survival of 12.9 months versus 10.5 months.

However, adding tremelimumab to durvalumab and platinum-etoposide did not provide a significant survival benefit, indicating that durvalumab plus platinum-etoposide should be considered the new standard of care for first-line treatment of ES-SCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Goldman, JW., Dvorkin, M., Chen, Y., et al.[2021]

In a phase III study with 453 patients, pembrolizumab combined with etoposide and platinum significantly improved progression-free survival (PFS) compared to placebo plus etoposide and platinum, with a 12-month PFS of 13.6% versus 3.1%.

While pembrolizumab plus EP also prolonged overall survival (OS), the results did not meet the predefined significance threshold; however, the treatment showed a favorable safety profile with no unexpected toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab or Placebo Plus Etoposide and Platinum as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer: Randomized, Double-Blind, Phase III KEYNOTE-604 Study. Rudin, CM., Awad, MM., Navarro, A., et al.[2021]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

The combination of lenvatinib and pembrolizumab shows significant clinical benefits for patients with endometrial carcinoma, with a safety profile consistent with each drug's individual use, primarily involving manageable side effects like hypertension and hypothyroidism.

Effective management of lenvatinib's common adverse events is crucial to maximize its efficacy, as most side effects can be prevented or mitigated through proactive monitoring and intervention during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing the use of lenvatinib in combination with pembrolizumab in patients with advanced endometrial carcinoma. Lorusso, D., Danesi, R., Locati, LD., et al.[2023]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

References

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

The current role and future prospects of paclitaxel in the treatment of small cell lung cancer. [2015]

2. Ireland pubmed.ncbi.nlm.nih.gov

A phase II study of pembrolizumab and paclitaxel in patients with relapsed or refractory small-cell lung cancer. [2020]

3. China pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). [2023]

4. England pubmed.ncbi.nlm.nih.gov

Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. [2021]

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

Pembrolizumab or Placebo Plus Etoposide and Platinum as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer: Randomized, Double-Blind, Phase III KEYNOTE-604 Study. [2021]

6. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Optimizing the use of lenvatinib in combination with pembrolizumab in patients with advanced endometrial carcinoma. [2023]

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

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]

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

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]