Pembrolizumab Combo for Lung Cancer

No longer recruiting at 97 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, Corticosteroids, Antineoplastics, others

Disqualifiers: Cardiovascular impairment, Active infection, CNS metastases, 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: Unknown

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for advanced non-small cell lung cancer (NSCLC) in individuals who have not previously undergone chemotherapy for this condition. Participants will receive pembrolizumab, an immunotherapy drug, combined with one of three other drugs—quavonlimab, favezelimab, or lenvatinib—based on specific genetic markers. The goal is to evaluate the effectiveness of these combinations in shrinking tumors. Individuals with stage IV NSCLC who have not received any prior treatment for this advanced stage may be suitable candidates for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, providing an opportunity to benefit from cutting-edge therapies.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on systemic steroid therapy or any form of immunosuppressive therapy, you may need to stop or adjust it, as these are exclusion criteria.

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

Research has shown that the combination of pembrolizumab with favezelimab is generally safe. Studies reported no treatment-related deaths, indicating that serious side effects are rare.

For the pembrolizumab and lenvatinib combination, research indicates it can be safely used for certain cancers. Many patients have tolerated it well, though some side effects may occur.

The pembrolizumab and quavonlimab combination also shows promising safety results. Studies suggest that patients tolerate this combination without any new or unexpected safety issues.

These treatments are in a Phase 2 trial, meaning earlier studies have already tested their safety. This phase focuses more on efficacy, but safety remains closely monitored. Overall, these combinations are considered safe enough for further testing. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for lung cancer because they combine pembrolizumab, a powerful cancer-fighting drug, with other promising agents like favezelimab, lenvatinib, and quavonlimab. Pembrolizumab is an immune checkpoint inhibitor that helps the immune system attack cancer cells, and when combined with favezelimab, another immune checkpoint inhibitor, or quavonlimab, it may enhance this immune response even further. Lenvatinib, on the other hand, is a targeted therapy that blocks proteins that help tumors grow blood vessels, potentially starving the cancer. These combinations could offer more effective and potentially longer-lasting responses compared to current treatments, which typically involve chemotherapy or single-agent immunotherapies.

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

This trial will evaluate different combinations of pembrolizumab with other drugs for treating advanced non-small cell lung cancer (NSCLC). Participants in one arm will receive pembrolizumab combined with quavonlimab, a combination that research has shown to be promising, with 28% to 40% of patients experiencing tumor shrinkage in previous studies. Another arm will test pembrolizumab with favezelimab, which earlier research indicates can boost the immune system, though it may also lead to more immune-related side effects. A separate arm will study pembrolizumab with lenvatinib, a combination that has had mixed results for NSCLC, despite being approved for other cancers. Each combination in this trial aims to help the immune system fight lung cancer more effectively. ^{1 2 4 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

Adults with advanced non-small cell lung cancer (NSCLC) who haven't had systemic therapy for it can join. They must have specific gene profiles, good organ function, and an ECOG status of 0-1. Men and women must agree to contraception; women cannot be pregnant or breastfeeding. People with certain heart conditions, active infections like hepatitis B/C or HIV, recent major surgery, other cancers within 3 years, severe allergies to trial drugs or their ingredients are excluded.

Inclusion Criteria

The doctors can see and measure your disease using a specific assessment method called RECIST 1.1.

I have provided a sample of my tumor that has not been treated with radiation.

My cancer does not require treatment targeting EGFR, ALK, ROS1, or B-Raf mutations.

Exclusion Criteria

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

My cancer has spread to major blood vessels.

My NSCLC can potentially be cured with surgery or targeted radiation.

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 either quavonlimab, favezelimab, or lenvatinib until disease progression or for up to 2 years

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Favezelimab
• Lenvatinib
• Pembrolizumab
• Quavonlimab

Trial Overview The study tests pembrolizumab combined with quavonlimab, favezelimab, or lenvatinib in NSCLC patients based on their gene expression profile (GEP) and tumor mutational burden (TMB). The goal is to see if these combinations improve response rates compared to historical data for different GEP/TMB groups.

How Is the Trial Designed?

Group I: GEP low TMB low: Pembrolizumab + Quavonlimab Experimental Treatment 2 Interventions

Participants receive pembrolizumab 200 mg Q3W plus quavonlimab at the Recommended Phase 2 Dose (\[RP2D\], dose and schedule based on study NCT03179436) until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years).

Group II: GEP low TMB low: Pembrolizumab + Lenvatinib Experimental Treatment 2 Interventions

Participants receive pembrolizumab 200 mg Q3W plus lenvatinib 20 mg once daily until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years). Participants completing 35 infusions of pembrolizumab may continue with lenvatinib alone until disease progression or toxicity.

Group III: GEP low TMB low: Pembrolizumab + Favezelimab Experimental Treatment 2 Interventions

Participants receive pembrolizumab 200 mg Q3W plus favezelimab 200 mg or 800 mg Q3W until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years).

Group IV: GEP low TMB hi: Pembrolizumab + Quavonlimab Experimental Treatment 2 Interventions

Participants receive pembrolizumab 200 mg Q3W plus quavonlimab at the RP2D (dose and schedule based on study NCT03179436) until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years).

Group V: GEP low TMB hi: Pembrolizumab + Lenvatinib Experimental Treatment 2 Interventions

Participants receive pembrolizumab 200 mg Q3W plus lenvatinib 20 mg once daily until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years). Participants completing 35 infusions of pembrolizumab may continue with lenvatinib alone until disease progression or toxicity.

Group VI: GEP low TMB hi: Pembrolizumab + Favezelimab Experimental Treatment 2 Interventions

Participants receive pembrolizumab 200 mg Q3W plus favezelimab 200 mg or 800 mg Q3W until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years).

Group VII: GEP hi TMB low: Pembrolizumab + Quavonlimab Experimental Treatment 2 Interventions

Participants receive pembrolizumab 200 mg Q3W plus quavonlimab at the RP2D (dose and schedule based on study NCT03179436) until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years).

Group VIII: GEP hi TMB low: Pembrolizumab + Lenvatinib Experimental Treatment 2 Interventions

Participants receive pembrolizumab 200 mg Q3W plus lenvatinib 20 mg once daily until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years). Participants completing 35 infusions of pembrolizumab may continue with lenvatinib alone until disease progression or toxicity.

Group IX: GEP hi TMB low: Pembrolizumab + Favezelimab Experimental Treatment 2 Interventions

Participants receive pembrolizumab 200 mg Q3W plus favezelimab 200 mg or 800 mg Q3W until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years).

Group X: GEP hi TMB hi: Pembrolizumab + Quavonlimab Experimental Treatment 2 Interventions

Participants receive pembrolizumab 200 mg Q3W plus quavonlimab at the RP2D (dose and schedule based on study NCT03179436) until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years).

Group XI: GEP hi TMB hi: Pembrolizumab + Lenvatinib Experimental Treatment 2 Interventions

Participants receive pembrolizumab 200 mg Q3W plus lenvatinib 20 mg once daily until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years). Participants completing 35 infusions of pembrolizumab may continue with lenvatinib alone until disease progression or toxicity.

Group XII: GEP hi TMB hi: Pembrolizumab + Favezelimab Experimental Treatment 2 Interventions

Participants receive pembrolizumab 200 mg Q3W plus favezelimab 200 mg or 800 mg Q3W until disease progression, or until the participant has received 35 administrations of pembrolizumab (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

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]

The combination of lenvatinib, a multikinase inhibitor, and pembrolizumab, a PD-1 inhibitor, shows promising antitumor activity and durable responses in various solid tumors, as indicated by preliminary results from the LEAP clinical trial program.

This combination therapy has a manageable safety profile, suggesting it could be a valuable new treatment option for solid cancers that currently have limited therapeutic alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The LEAP program: lenvatinib plus pembrolizumab for the treatment of advanced solid tumors. Taylor, MH., Schmidt, EV., Dutcus, C., et al.[2021]

In a study of 43 patients with recurrent endometrial cancer treated with lenvatinib and pembrolizumab, 84% experienced significant adverse events (AEs), with hypertension and weight loss being the most common.

Patients starting on a reduced dose of lenvatinib (10 mg or 14 mg) had significantly longer progression-free survival compared to those on the standard dose (20 mg), suggesting that dose optimization may improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events and oncologic outcomes with combination lenvatinib and pembrolizumab for the treatment of recurrent endometrial cancer. Zammarrelli, WA., Ma, W., Espino, K., et al.[2023]

The ongoing KEYNOTE-495/KeyImPaCT study is evaluating the effectiveness of pembrolizumab combined with other therapies in advanced non-small cell lung cancer (NSCLC), with results showing varying objective response rates (ORR) based on tumor characteristics, ranging from 0-12% in low T-cell-inflamed groups to 50-60% in high T-cell-inflamed groups.

The study confirms that assessing T-cell-inflamed gene expression profiles (TcellinfGEP) and tumor mutational burden (TMB) can help identify which patients are more likely to benefit from pembrolizumab-based treatments, while the safety profiles of the combinations remain consistent with previous findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomarker-directed, pembrolizumab-based combination therapy in non-small cell lung cancer: phase 2 KEYNOTE-495/KeyImPaCT trial interim results. Gutierrez, M., Lam, WS., Hellmann, MD., et al.[2023]

The combination of pembrolizumab and lenvatinib demonstrated significantly higher objective response rates (ORRs) and progression-free survival (mPFS) compared to their individual therapies in solid cancers, with ORRs reaching up to 70% in renal cell carcinoma.

Despite a high incidence of adverse events (68.0% for the combination therapy), the toxicities were manageable and no unexpected safety issues were reported, indicating that the combination therapy is both effective and relatively safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of pembrolizumab plus lenvatinib versus pembrolizumab and lenvatinib monotherapies in cancers: A systematic review. Mo, DC., Luo, PH., Huang, SX., et al.[2021]

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]

The combination of vibostolimab and pembrolizumab is well tolerated by patients, indicating a favorable safety profile for this treatment regimen.

This combination therapy demonstrates antitumor activity, suggesting it may be an effective option for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Anti-TIGIT Antibody with a PD-1 Inhibitor Shows Promise in Solid Tumors. [2022]

In the phase II LEAP-004 study involving 103 patients with advanced melanoma who had disease progression on PD-1 inhibitors, the combination of lenvatinib and pembrolizumab achieved an objective response rate of 21.4%, indicating its potential effectiveness in this challenging population.

The treatment demonstrated a median progression-free survival of 4.2 months and an overall survival of 14.0 months, with a manageable safety profile, including a 45.6% incidence of grade 3-5 adverse events, primarily hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II LEAP-004 Study of Lenvatinib Plus Pembrolizumab for Melanoma With Confirmed Progression on a Programmed Cell Death Protein-1 or Programmed Death Ligand 1 Inhibitor Given as Monotherapy or in Combination. Arance, A., de la Cruz-Merino, L., Petrella, TM., et al.[2023]

In a phase 2 study involving 38 patients with pleural mesothelioma, the combination of pembrolizumab and lenvatinib resulted in a promising objective response rate of 58%, indicating significant anti-tumor activity after prior chemotherapy.

However, the treatment was associated with considerable toxicity, with 26% of patients experiencing serious treatment-related adverse events, including one death, highlighting the need for careful monitoring and supportive care during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus lenvatinib in second-line and third-line patients with pleural mesothelioma (PEMMELA): a single-arm phase 2 study. Douma, LH., Lalezari, F., van der Noort, V., 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37429923/

phase 2 KEYNOTE-495/KeyImPaCT trial interim results Although pembrolizumab confers clinical benefit in non-small cell lung cancer (NSCLC), only a subset of patients will respond due to a ...

2. merck.com merck.com/news/merck-provides-update-on-keyvibe-and-keyform-clinical-development-programs-evaluating-investigational-vibostolimab-and-favezelimab-fixed-dose-combinations-with-pembrolizumab/

Merck Provides Update on KeyVibe and KEYFORM ... As expected with dual checkpoint inhibitor therapy, more immune-related adverse events were observed with the fixed-dose combination than with ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03516981

A Study of Biomarker-Directed, Pembrolizumab (MK-3475) ... This study will investigate the utility of biomarker-based triage for study participants with advanced non-small cell lung cancer (NSCLC) without prior ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.LBA248

The phase 3, randomized KEYFORM-007 study. The phase 3 KEYFORM-007 study (NCT05064059) evaluated the efficacy and safety of co-formulated fave/pembro vs standard-of-care (SOC) in PD-L1–positive MSS/pMMR ...

5. clinicaltrialsarena.com clinicaltrialsarena.com/news/msd-phase-iii-pembrolizumab/

MSD reports outcomes from Phase III trial of pembrolizumab MSD has reported positive topline outcomes from the Phase III study of subcutaneous pembrolizumab in conjunction with chemotherapy for ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.7056

A phase 1/2 study of favezelimab in combination with ... Favezelimab + pembrolizumab continued to demonstrate manageable safety and antitumor activity in pts with heavily pretreated anti–PD-1–refractory cHL.

7. esmoopen.com esmoopen.com/article/S2059-7029(22)00273-3/fulltext

A first-in-human study of the anti-LAG-3 antibody ... Favezelimab with or without pembrolizumab had a manageable safety profile, with no treatment-related deaths. Promising antitumor activity was ...