Pembrolizumab + Chemotherapy for Non-Small Cell Lung Cancer

Recruiting at 39 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Small cell lung cancer, Immunodeficiency, Active CNS metastases, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: Up to 2 years

450 Participants Needed

Trial Summary

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 immunosuppressive therapy or have had recent chemotherapy or biological cancer therapy, you may need to stop or adjust those treatments before starting the trial.

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

Research shows that adding pembrolizumab to chemotherapy significantly improves survival and response rates in patients with advanced non-small cell lung cancer, with manageable side effects. ^{1 2 3 4 5}

Is the combination of Pembrolizumab and chemotherapy safe for humans?

Pembrolizumab, when used with chemotherapy, has been generally safe but can cause side effects like pneumonitis (lung inflammation) in 1%-5% of patients and rare cases of type 1 diabetes (a condition where the body can't produce insulin). These side effects are part of the immune-related adverse events that can occur with this treatment. ^{1 5 6 7 8}

What makes the drug combination of Pembrolizumab and chemotherapy unique for treating non-small cell lung cancer?

This drug combination is unique because Pembrolizumab, an immune system booster, is used alongside chemotherapy to improve survival rates in non-small cell lung cancer patients compared to chemotherapy alone. Pembrolizumab targets the PD-1 pathway, enhancing the body's immune response against cancer cells. ^{1 5 6 9 10}

What is the purpose of this trial?

The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) with or without chemotherapy in combination with vibostolimab (MK-7684), boserolimab (MK-5890), MK-4830, MK-0482, I-DXd, or HER3-DXd in treatment-naïve participants with advanced squamous or non-squamous NSCLC. This study is one of the pembrolizumab substudies being conducted under one pembrolizumab umbrella master protocol (MK-3475-U01/KEYMAKER-U01).

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for adults with advanced non-small cell lung cancer (NSCLC) who haven't had treatment before. They should not be eligible for approved targeted therapies, have good organ function, and agree to use contraception. Pregnant or breastfeeding individuals, those with certain heart conditions, active infections, recent major surgery or live vaccines are excluded.

Inclusion Criteria

Is able to complete all screening procedures within the 35-day screening window

I agree to use birth control and not donate sperm during and up to 6 months after treatment.

I can provide a recent or archived tumor sample not previously treated with radiation.

Exclusion Criteria

I am allergic to carboplatin, paclitaxel, pemetrexed, or their ingredients.

I have a GI condition or liver issues that could affect medication absorption.

I have been diagnosed with small cell lung cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab with or without chemotherapy in combination with investigational agents for up to 2 years

Up to 2 years

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 24 months

Treatment Details

Interventions

• Boserolimab
• Carboplatin
• MK-4830
• MK-5890
• Paclitaxel
• Pembrolizumab
• Pemetrexed
• Vibostolimab

Trial Overview The study tests the effectiveness and safety of pembrolizumab combined with chemotherapy plus one of four investigational agents (vibostolimab, boserolimab, MK-4830, or MK-0482) in patients with untreated advanced NSCLC. It's part of a larger research project exploring pembrolizumab treatments.

Participant Groups

Group I: Part B: Pembrolizumab + I-DXd Experimental Treatment 2 Interventions

On Day 1 of each 3-week cycle, participants with squamous and nonsquamous NSCLC will receive pembrolizumab 200 mg IV for up to 2 years, PLUS I-DXd in escalating doses until progressive disease or toxicity.

Group II: Part B: Pembrolizumab + Carboplatin + I-DXd Experimental Treatment 3 Interventions

On Day 1 of each 3-week cycle, participants will receive pembrolizumab 200 mg IV for up to 2 years, PLUS carboplatin AUC 5-6 up to 4 cycles PLUS I-DXd IV in escalating doses until PD or toxicity.

Group III: Part B: Pembrolizumab + Carboplatin + HER3-DXd Experimental Treatment 3 Interventions

On Day 1 of each 3-week cycle, participants will receive pembrolizumab 200 mg IV for up to 2 years, PLUS carboplatin AUC 5-6 up to 4 cycles PLUS HER3-DXd IV in escalating doses until PD or toxicity.

Group IV: Part A: Pembrolizumab+Vibostolimab+Carboplatin + Pemetrexed Experimental Treatment 4 Interventions

On Day 1 of each 3-week cycle, participants with nonsquamous NSCLC receive pembrolizumab 200 mg IV PLUS vibostolimab IV PLUS carboplatin AUC 5 IV PLUS pemetrexed 500 mg/m\^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS vibostolimab IV PLUS pemetrexed 500 mg/m\^2 IV in Cycles 5-35 (total treatment duration: up to approximately 2 years).

Group V: Part A: Pembrolizumab+Vibostolimab+Carboplatin + Paclitaxel Experimental Treatment 4 Interventions

On Day 1 of each 3-week cycle, participants with squamous NSCLC receive pembrolizumab 200 mg intravenously (IV) PLUS vibostolimab IV PLUS carboplatin Area Under the Concentration-Time Curve (AUC) 6 IV PLUS paclitaxel 200 mg/m\^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS vibostolimab IV in Cycles 5-35 (total treatment duration: up to approximately 2 years).

Group VI: Part A: Pembrolizumab+MK-4830+Carboplatin+Pemetrexed Experimental Treatment 4 Interventions

On Day 1 of each 3-week cycle, participants with nonsquamous NSCLC receive pembrolizumab 200 mg IV PLUS MK-4830 IV PLUS carboplatin AUC 5 IV PLUS pemetrexed 500 mg/m\^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS MK-4830 IV PLUS pemetrexed 500 mg/m\^2 IV in Cycles 5-35 (total treatment duration: up to approximately 2 years).

Group VII: Part A: Pembrolizumab+MK-4830+Carboplatin+Paclitaxel Experimental Treatment 4 Interventions

On Day 1 of each 3-week cycle, participants with squamous NSCLC receive pembrolizumab 200 mg IV PLUS MK-4830 IV PLUS carboplatin AUC 6 IV PLUS paclitaxel 200 mg/m\^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS MK-4830 IV in Cycles 5-35 (total treatment duration: up to approximately 2 years).

Group VIII: Part A: Pembrolizumab+MK-0482+Carboplatin+Pemetrexed Experimental Treatment 3 Interventions

On Day 1 of each 3-week cycle, participants with nonsquamous NSCLC receive pembrolizumab 200 mg IV PLUS MK-0482 IV PLUS carboplatin AUC 5 IV PLUS pemetrexed 500 mg/m\^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS MK-0482 IV PLUS pemetrexed 500 mg/m\^2 IV in Cycles 5-35 (total treatment duration: up to approximately 2 years).

Group IX: Part A: Pembrolizumab+MK-0482+Carboplatin+Paclitaxel Experimental Treatment 3 Interventions

On Day 1 of each 3-week cycle, participants with squamous NSCLC receive pembrolizumab 200 mg IV PLUS MK-0482 IV PLUS carboplatin AUC 6 IV PLUS paclitaxel 200 mg/m\^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS MK-0482 IV in Cycles 5-35 (total treatment duration: up to approximately 2 years).

Group X: Part A: Pembrolizumab+Boserolimab+Carboplatin+Pemetrexed Experimental Treatment 4 Interventions

On Day 1 of each 3-week cycle, participants with nonsquamous NSCLC receive pembrolizumab 200 mg IV PLUS carboplatin AUC 5 IV PLUS pemetrexed 500 mg/m\^2 IV PLUS boserolimab IV on Day 1 every 6 weeks (every other 3-week cycle) (Q6W) in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV Q3W PLUS pemetrexed 500 mg/m\^2 IV Q3W PLUS boserolimab IV Q6W from Cycles 5 up to Cycle 35 (total treatment duration: up to approximately 2 years).

Group XI: Part A: Pembrolizumab+Boserolimab+Carboplatin+Paclitaxel Experimental Treatment 4 Interventions

On Day 1 of each 3-week cycle, participants with squamous NSCLC receive pembrolizumab 200 mg IV PLUS carboplatin AUC 6 IV PLUS paclitaxel 200 mg/m\^2 IV PLUS boserolimab IV on Day 1 every 6 weeks (every other 3-week cycle) (Q6W) in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV Q3W PLUS boserolimab IV Q6W from Cycles 5 up to Cycle 35 (total treatment duration: up to approximately 2 years).

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

Daiichi Sankyo

Industry Sponsor

Trials

443

Recruited

493,000+

Hiroyuki Okuzawa

Daiichi Sankyo

Chief Executive Officer

Degree in Social Sciences from Hitotsubashi University

Yuki Abe

Daiichi Sankyo

Chief Medical Officer since 2023

MD

Findings from Research

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 KEYNOTE-407 study involving 1107 patients with untreated metastatic squamous non-small-cell lung cancer, the addition of pembrolizumab to chemotherapy significantly improved overall survival and quality of life without increasing severe toxicity.

Patients receiving pembrolizumab reported better health-related quality of life scores at weeks 9 and 18 compared to those receiving placebo, indicating that pembrolizumab enhances patient well-being while maintaining effective cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-Related Quality of Life With Carboplatin-Paclitaxel or nab-Paclitaxel With or Without Pembrolizumab in Patients With Metastatic Squamous Non-Small-Cell Lung Cancer. Mazieres, J., Kowalski, D., Luft, A., et al.[2020]

In a phase II study involving 167 patients with stage IV squamous non-small-cell lung cancer, the combination of necitumumab with paclitaxel-carboplatin chemotherapy resulted in a higher objective response rate (48.9%) compared to chemotherapy alone (40.0%).

The safety profile of necitumumab was consistent with other EGFR monoclonal antibodies, with increased rates of hypomagnesemia and rash, but overall adverse events were low, indicating that necitumumab can be safely combined with chemotherapy for improved treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Open-Label, Randomized, Controlled Phase II Study of Paclitaxel-Carboplatin Chemotherapy With Necitumumab Versus Paclitaxel-Carboplatin Alone in First-Line Treatment of Patients With Stage IV Squamous Non-Small-Cell Lung Cancer. Spigel, DR., Luft, A., Depenbrock, H., et al.[2022]

In a systematic review and network meta-analysis of first-line treatments for metastatic nonsquamous non-small-cell lung cancer (NSq-NSCLC), the combination of pembrolizumab, pemetrexed, and platinum showed a statistically significant improvement in overall survival compared to various other regimens, with hazard ratios ranging from 0.42 to 0.62.

This combination therapy had a 95.6% probability of being the most effective treatment option for overall survival in patients without known targetable mutations, indicating its strong potential as a first-line treatment for this type of lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus chemotherapy for first-line treatment of metastatic nonsquamous non-small-cell lung cancer: a network meta-analysis. Frederickson, AM., Arndorfer, S., Zhang, I., 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]

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, 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, when combined with carboplatin and pemetrexed, significantly improves overall and progression-free survival rates in patients with non-small cell lung cancer (NSCLC), demonstrating its efficacy as a treatment option.

This case report highlights a unique instance of immune-mediated sarcoidosis developing in a patient with NSCLC after receiving pembrolizumab, indicating potential immune-related side effects of this therapy that require further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary Sarcoidosis Activation following Neoadjuvant Pembrolizumab plus Chemotherapy Combination Therapy in a Patient with Non-Small Cell Lung Cancer: A Case Report. Fakhri, G., Akel, R., Salem, Z., et al.[2022]

In a study of 100 patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab, further stratification of PD-L1 tumor proportion score (TPS) beyond 50% did not significantly affect progression-free survival (PFS).

Smoking status was associated with improved PFS, while prior radiotherapy was linked to decreased PFS, indicating that these factors, along with performance status, may serve as important biomarkers for predicting response to pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab monotherapy for non-small cell lung cancer (NSCLC): can patient stratification be improved in the UK Tayside population? A retrospective cohort study. Mander, ES., Merrick, CB., Nicholson, HA., et al.[2023]

References

1. 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]

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

Health-Related Quality of Life With Carboplatin-Paclitaxel or nab-Paclitaxel With or Without Pembrolizumab in Patients With Metastatic Squamous Non-Small-Cell Lung Cancer. [2020]

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

An Open-Label, Randomized, Controlled Phase II Study of Paclitaxel-Carboplatin Chemotherapy With Necitumumab Versus Paclitaxel-Carboplatin Alone in First-Line Treatment of Patients With Stage IV Squamous Non-Small-Cell Lung Cancer. [2022]

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

Pembrolizumab plus chemotherapy for first-line treatment of metastatic nonsquamous non-small-cell lung cancer: a network meta-analysis. [2022]

5. 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]

6. England pubmed.ncbi.nlm.nih.gov

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

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

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

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

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

9. Switzerland pubmed.ncbi.nlm.nih.gov

Pulmonary Sarcoidosis Activation following Neoadjuvant Pembrolizumab plus Chemotherapy Combination Therapy in a Patient with Non-Small Cell Lung Cancer: A Case Report. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab monotherapy for non-small cell lung cancer (NSCLC): can patient stratification be improved in the UK Tayside population? A retrospective cohort study. [2023]