Pembrolizumab Combination Therapy for Non-Small Cell Lung Cancer

Recruiting at 43 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme Corp.

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: 1

Duration: 24 months

135 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) in combination with boserolimab (MK-5890), MK-4830, MK-0482 in participants with advanced squamous or non-squamous NSCLC that have been previously treated with anti-PD-L1 therapy. This study is one of three pembrolizumab substudies being conducted under one pembrolizumab umbrella master protocol (MK-3475-U01/KEYMAKER-U01).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on chronic systemic steroid therapy or any form of immunosuppressive therapy, you may need to stop these at least 7 days before starting the trial.

What data supports the effectiveness of the drug Pembrolizumab for non-small cell lung cancer?

Research shows that Pembrolizumab, a drug that helps the immune system fight cancer, has been effective in treating non-small cell lung cancer, especially in patients with high levels of a protein called PD-L1. It has shown positive results in both early and advanced stages of the disease. ^{1 2 3 4 5}

Is pembrolizumab generally safe for humans?

Pembrolizumab has been associated with some immune-related side effects, such as type 1 diabetes in 0.2% of cases and pneumonitis in 1%-5% of patients. Common side effects include fatigue, cough, nausea, and rash, but the benefits in treating serious conditions like cancer often outweigh these risks. ^{3 4 6 7 8}

What makes the pembrolizumab combination therapy unique for non-small cell lung cancer?

This treatment is unique because it combines pembrolizumab, a drug that helps the immune system fight cancer by blocking a pathway that tumors use to hide, with other investigational drugs like Boserolimab, MK-0482, MK-4830, and MK-5890, potentially enhancing its effectiveness against non-small cell lung cancer. ^{1 2 3 4 9}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for adults with Stage IV NSCLC who have already tried anti-PD-L1 therapy and chemotherapy but their cancer has gotten worse. They must have good organ function, be able to provide a tumor tissue sample, not be pregnant or breastfeeding, agree to use contraception, and not have severe immune reactions from previous immunotherapies.

Inclusion Criteria

My lung cancer is confirmed to be at stage IV.

My lung cancer is non-squamous and I can't have targeted therapy.

My organs are functioning well enough for treatment.

Exclusion Criteria

You had a very bad allergic reaction to a type of medication called monoclonal antibodies, including pembrolizumab.

I had major surgery less than 3 weeks ago.

You have taken part in Substudies 1 or 2.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab in combination with investigational agents (boserolimab, MK-4830, or MK-0482) every 3 weeks for up to 35 cycles (approximately 2 years)

24 months

1 visit every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Long-term follow-up

Participants are monitored for adverse events and progression-free survival

Up to 27 months

Treatment Details

Interventions

• Boserolimab
• MK-0482
• MK-4830
• MK-5890
• Pembrolizumab

Trial Overview The study tests the safety and effectiveness of pembrolizumab combined with other investigational drugs (boserolimab, MK-4830, MK-0482) in patients whose lung cancer has progressed after treatment with anti-PD-L1 therapy. It's part of a larger research project exploring different pembrolizumab combinations.

Participant Groups

Group I: Pembrolizumab + MK-4830 Experimental Treatment 2 Interventions

On Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS MK-4830 IV for a maximum of 35 cycles (approximately 2 years).

Group II: Pembrolizumab + MK-0482 Experimental Treatment 2 Interventions

On Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS MK-0482 IV for a maximum of 35 cycles (approximately 2 years).

Group III: Boserolimab + Pembrolizumab Experimental Treatment 4 Interventions

On Day 1 of each 3-week cycle, participants receive pembrolizumab 200 mg intravenously (IV) PLUS boserolimab IV for a maximum of 35 cycles (approximately 2 years). All participants are premedicated 1.5 hours (±30 minutes) before infusion of boserolimab with 50 mg oral (PO) diphenhydramine (or equivalent dose of antihistamine) and 500-1000 mg of acetaminophen PO (or equivalent dose of analgesic).

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

In a Phase 2 study involving 35 patients with non-small cell lung cancer, neoadjuvant pembrolizumab was found to be safe and well tolerated, with only one surgery delay due to thyroiditis and no mortality within 90 days post-surgery.

The study showed a high rate of R0 resection (88%) and a major pathologic response in 28% of patients, indicating that pembrolizumab may be more effective than standard neoadjuvant chemotherapy in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. Tong, BC., Gu, L., Wang, X., et al.[2022]

In a study of 153 patients with non-small-cell lung cancer treated with pembrolizumab, the median overall survival was 22 months, and the treatment showed similar efficacy to clinical trials, particularly in patients meeting KEYNOTE-024 trial criteria.

Patients with a performance status (PS) of 2 or higher, symptomatic brain metastases, or those on steroids had significantly reduced survival, indicating that while pembrolizumab can be effective, it may not benefit the most frail patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab as First-Line Palliative Therapy in PD-L1 Overexpressing (≥ 50%) NSCLC: Real-world Results with Special Focus on PS ≥ 2, Brain Metastases, and Steroids. Frost, N., Kollmeier, J., Misch, D., et al.[2022]

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]

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]

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

References

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

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. [2022]

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

Pembrolizumab as First-Line Palliative Therapy in PD-L1 Overexpressing (≥ 50%) NSCLC: Real-world Results with Special Focus on PS ≥ 2, Brain Metastases, and Steroids. [2022]

3. 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]

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

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

5. France pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017]

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

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

9. Ireland pubmed.ncbi.nlm.nih.gov

Clinical efficacy and safety of individualized pembrolizumab administration based on pharmacokinetic in advanced non-small cell lung cancer: A prospective exploratory clinical trial. [2023]