Pembrolizumab + Chemotherapy for Small Cell Lung Cancer

Recruiting at 65 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

126 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the effectiveness of combining pembrolizumab (Keytruda) with new treatments and standard chemotherapy for individuals with extensive-stage small cell lung cancer (ES-SCLC). The study will explore whether these combinations can improve outcomes for this type of lung cancer, which has spread widely in the body. Individuals with confirmed ES-SCLC who have not received prior treatment for their cancer might be suitable candidates for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in cancer care.

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.

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

A previous study tested the safety of pembrolizumab (a type of immune therapy) combined with MK-4830. The results showed it was generally well-tolerated, with manageable side effects like tiredness and nausea.

Research has shown that using boserolimab with pembrolizumab has an acceptable safety profile. Some patients experienced mild to moderate side effects, such as fatigue and cough.

Studies have found that the combination of pembrolizumab and lenvatinib is also generally safe. Some people reported side effects like high blood pressure and diarrhea, but these are usually treatable.

All these treatments are being tested in a Phase 2 trial. This phase indicates that safety in humans has been observed, but more information is needed to confirm it. Participants should discuss potential risks with their healthcare provider before joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for small cell lung cancer because they explore new combinations of immunotherapy and chemotherapy, offering potential advances over existing options. Pembrolizumab, in combination with MK-4830 or boserolimab, targets the immune system, aiming to enhance its ability to fight cancer cells more effectively than standard treatments, such as platinum-based chemotherapy alone. Lenvatinib adds another layer by potentially disrupting the blood supply to tumors, which could starve them of the nutrients they need to grow. Each of these combinations represents a unique approach to enhancing the body's natural defenses against cancer, which could lead to improved outcomes for patients.

What evidence suggests that this trial's treatments could be effective for small cell lung cancer?

In this trial, participants will receive different treatment combinations to evaluate their effectiveness in managing small cell lung cancer. One arm will test pembrolizumab combined with MK-4830 and chemotherapy, building on previous studies where pembrolizumab with chemotherapy helped patients live longer without disease progression. Another arm will explore the combination of pembrolizumab with boserolimab and chemotherapy, with early research indicating potential benefits. Additionally, a separate arm will assess pembrolizumab with lenvatinib and chemotherapy, which is being tested for its ability to improve patient outcomes, with promising early findings. These combinations aim to strengthen the immune system to fight cancer more effectively, offering hope for improved management of small cell lung cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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, 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]

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]

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 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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32468956/

Randomized, Double-Blind, Phase III KEYNOTE-604 Study Pembrolizumab plus EP significantly improved PFS compared with placebo plus EP as first-line therapy for patients with ES-SCLC.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04924101?intr=MK-4830&aggFilters=phase:2&rank=10

Efficacy and Safety of Pembrolizumab Plus Investigational ... The purpose of this study is to evaluate the use of investigational agents (MK-4830, boserolimab (MK-5890) and lenvatinib (MK-7902)) in combination with ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03066778

NCT03066778 | A Study of Pembrolizumab (MK-3475) in ... The purpose of this study is to assess the safety and efficacy of pembrolizumab plus standard of care (SOC) chemotherapy (etoposide/platinum [EP])

4. clinicaltrials.eu clinicaltrials.eu/trial/study-on-pembrolizumab-etoposide-and-cisplatin-or-carboplatin-for-first-line-treatment-in-patients-with-extensive-stage-small-cell-lung-cancer/

Study on Pembrolizumab, Etoposide, and Cisplatin or ... This clinical trial evaluates the safety and effectiveness of Pembrolizumab, Etoposide, and either Cisplatin or Carboplatin in the ...

5. humanforschung-schweiz.ch humanforschung-schweiz.ch/en/trial-search/study-detail/55416/translate/en/?cHash=8948e46434dce40873a1c371700b59a3

A Phase 2 study to assess the efficacy and safety of ... Recent clinical research data have shown that a combination of chemotherapy and immunotherapy as first-line therapy can improve treatment efficacy for small ...

6. merck.com merck.com/news/five-year-data-for-mercks-keytruda-pembrolizumab-plus-chemotherapy-showed-sustained-survival-benefit-versus-chemotherapy-alone-in-two-studies-for-metastatic-non-small-cell-lung-cancer-nsclc/

Five-Year Data for Merck's KEYTRUDA® (pembrolizumab ... Five-year overall survival rate of 19.4% and 18.4% for KEYTRUDA plus chemotherapy in KEYNOTE-189 and KEYNOTE-407, respectively.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36824127/

A systematic review and meta-analysis In RCTs, pembrolizumab monotherapy or in combination with chemotherapy is more effective and safer than chemotherapy for advanced NSCLC.

8. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-08822

Efficacy and Safety of Pembrolizumab Plus Investigational ... The purpose of this study is to evaluate the use of investigational agents (MK-4830, boserolimab (MK-5890) and lenvatinib (MK-7902)) in combination with ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT03396445

Study of Boserolimab (MK-5890) as Monotherapy and in ... The purpose of this study is to assess the safety and pharmacokinetics of boserolimab (MK-5890) when administered alone and in combination with pembrolizumab ( ...

10. ascopubs.org ascopubs.org/doi/10.1200/jco.2015.33.15_suppl.7502

Pembrolizumab (MK-3475) in patients (pts) with extensive- ... Pembrolizumab (MK-3475) in patients (pts) with extensive-stage small cell lung cancer (SCLC): Preliminary safety and efficacy results from ...