135 Participants Needed

Pembrolizumab Combination Therapy for Non-Small Cell Lung Cancer

Recruiting at 43 trial locations
TF
Overseen ByToll Free Number
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: Merck Sharp & Dohme Corp.
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

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.12345

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.34678

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.12349

Research Team

MD

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.
See 6 more

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.
See 18 more

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 OverviewThe 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
3Treatment groups
Experimental Treatment
Group I: Pembrolizumab + MK-4830Experimental Treatment2 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-0482Experimental Treatment2 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 + PembrolizumabExperimental Treatment4 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

Find a Clinic Near You

Who Is Running the Clinical Trial?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials
2,287
Recruited
4,582,000+
Chirfi Guindo profile image

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 profile image

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 profile image

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 profile image

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.
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.
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.
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]

References

Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. [2022]
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]
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]
[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017]
Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]
Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]
FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]
Clinical efficacy and safety of individualized pembrolizumab administration based on pharmacokinetic in advanced non-small cell lung cancer: A prospective exploratory clinical trial. [2023]