Pembrolizumab + Investigational Agents for Non-Small Cell Lung Cancer

No longer recruiting at 56 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: Steroids, Immunosuppressants, Chemotherapy, others

Disqualifiers: Small cell lung cancer, CNS metastases, Active infection, Cardiac 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: 1

Duration: Approximately 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of drugs, including pembrolizumab, to evaluate their effectiveness and safety for individuals with advanced non-small cell lung cancer (NSCLC) that has not been previously treated. The focus is on patients whose cancer is positive for PD-L1, a protein that helps cancer evade the immune system. Participants will receive pembrolizumab (also known as KEYTRUDA) with either MK-4830 or MK-0482 (both investigational agents) every three weeks. Suitable candidates have advanced stage IV NSCLC and have not received prior systemic treatment. As a Phase 2 trial, this research aims to measure the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

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 immunosuppressive therapy, you may need to stop these at least 7 days before starting the trial treatment.

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

Research has shown that combining pembrolizumab with MK-4830 and MK-0482 appears safe. Studies found that patients generally tolerated MK-4830 well when used with pembrolizumab, indicating relative safety. Additionally, there were signs it might help fight tumors, suggesting potential effectiveness.

For the combination of pembrolizumab with MK-0482, early research focuses on determining the right dose to ensure safety and tolerability. Scientists continue to study this combination to confirm its safety for patients.

Both MK-4830 and MK-0482 have undergone previous trials, passing safety checks at each stage. Although more research is needed, current data suggests that these treatments, when combined with pembrolizumab, have generally been well tolerated by participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a novel approach to tackling Non-Small Cell Lung Cancer (NSCLC). Both investigational agents, MK-0482 and MK-4830, are combined with pembrolizumab, a well-known immunotherapy drug. Unlike many standard treatments that target cancer cells directly, these combinations aim to enhance the body's immune response against cancer. MK-0482 and MK-4830 are designed to inhibit pathways that tumors use to hide from the immune system, potentially making the treatment more effective. This innovative strategy could lead to improved outcomes for patients by harnessing the power of the immune system in a new way.

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

In this trial, participants will receive either the combination of pembrolizumab and MK-4830 or the combination of pembrolizumab and MK-0482. Research has shown that pembrolizumab, when combined with MK-4830, effectively fights tumors in patients with advanced non-small cell lung cancer (NSCLC). Studies have found that patients generally tolerate this combination well, which is promising for its potential success. Pembrolizumab alone has already been proven to help NSCLC patients live longer, with long-term evidence supporting its use.

In early trials of the pembrolizumab and MK-0482 combination, researchers focused on ensuring safety and determining the right dose. Pembrolizumab by itself has shown a significant survival benefit compared to traditional chemotherapy for advanced NSCLC. This suggests that adding new drugs like MK-0482 might enhance its effectiveness, although more research is needed to confirm this. ^{2 6 7 8 9}

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 advanced Non-Small Cell Lung Cancer (NSCLC) that tests positive for PD-L1 and haven't had treatment before. They must have good organ function, agree to use contraception, and not be pregnant or breastfeeding. Excluded are those with certain infections, heart conditions, other cancers within 2 years, severe allergies to monoclonal antibodies, or prior treatments like chemotherapy.

Inclusion Criteria

I am not pregnant or breastfeeding and either cannot become pregnant or will use contraception for 120 days after treatment.

I have not had any treatment for my advanced lung cancer.

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

Exclusion Criteria

I have been diagnosed with HIV.

I have an autoimmune disease treated with medication in the last 2 years.

I have serious heart problems, including recent heart attacks or severe heart failure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab in combination with MK-4830 or MK-0482 intravenously every 3 weeks for up to 35 cycles

Approximately 24 months

1 visit every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

What Are the Treatments Tested in This Trial?

Interventions

• MK-0482
• MK-4830
• Pembrolizumab

Trial Overview The study examines the effectiveness and safety of pembrolizumab combined with MK-4830 or MK-0482 in patients who haven't been treated previously for their lung cancer. It's part of a larger research project looking at different substudies under one main protocol.

How Is the Trial Designed?

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)

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

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]

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, 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 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]

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]

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]

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]

In a study of 1,026 treatment-naïve patients with metastatic non-small-cell lung cancer (NSCLC) and PD-L1 expression of ≥50%, pembrolizumab showed an objective response rate of 44.5%, with median progression-free survival of 7.9 months and overall survival of 17.2 months.

Higher PD-L1 expression (≥90%) was linked to better treatment outcomes, while factors like poor performance status and the presence of bone or liver metastases were associated with worse clinical outcomes, indicating the importance of patient selection for pembrolizumab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinicopathologic correlates of first-line pembrolizumab effectiveness in patients with advanced NSCLC and a PD-L1 expression of ≥ 50. Cortellini, A., Tiseo, M., Banna, GL., et al.[2020]

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]

Citations

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A Study of MK-0482 as Monotherapy and in Combination ... This is a 2 part study. Part 1 is a dose escalation to determine the safety and tolerability and to establish a preliminary recommended Phase 2 dose (RP2D) ...

2. keytruda.com keytruda.com/non-small-cell-lung-cancer/clinical-trial-results/

Non–Small Cell Lung Cancer - Clinical Trial Results View the clinical trial results for this treatment option for certain people with non–small cell lung cancer.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33872070/

Five-Year Outcomes With Pembrolizumab Versus ... Pembrolizumab provides a durable, clinically meaningful long-term OS benefit versus chemotherapy as first-line therapy for metastatic NSCLC with PD-L1 tumor ...

4. keytrudahcp.com keytrudahcp.com/efficacy/

Efficacy Data for KEYTRUDA® (pembrolizumab) KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic non⁠–⁠small cell lung cancer (NSCLC) whose tumors express programmed ...

5. 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.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04165096

KEYMAKER-U01 Substudy 3: Efficacy and Safety Study of ... 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 ...

7. go.drugbank.com go.drugbank.com/drugs/DB17453/clinical_trials?conditions=DBCOND0030527&phase=2&purpose=treatment&status=completed

MK-0482 Completed Phase 2 Trials for Non-Small Cell ... KEYMAKER-U01 Substudy 3: Efficacy and Safety Study of Pembrolizumab (MK-3475) When Used With Investigational Agents in Participants With Advanced Non-small Cell ...

8. aacrjournals.org aacrjournals.org/cancerres/article/84/7_Supplement/CT249/742205/Abstract-CT249-Results-from-KEYMAKER-U01-substudy

Abstract CT249: Results from KEYMAKER-U01 substudy 3: a ... Results from KEYMAKER-U01 substudy 3: a phase 2 umbrella study of pembrolizumab plus investigational agents in patients with non-small-cell lung ...

9. delta.larvol.com delta.larvol.com/Products/?ProductId=b7659278-2640-41e3-a60d-7c8b2c82e4b4

MK-0482 / Merck (MSD) Trial completion • Brain Cancer • Breast Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ...