What side effects are associated with this type of intervention?

Common treatments for NSCLC, such as Pembrolizumab (Anti-PD-1) combined with Quavonlimab (Anti-CTLA-4), Favezelimab (Anti-LAG-3), or Lenvatinib (Multi-Kinase Inhibitor), are associated with several side effects. Pembrolizumab can cause immune-related adverse events like pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions. Quavonlimab, an Anti-CTLA-4 agent, may lead to immune-related side effects such as colitis, dermatitis, and hepatitis. Favezelimab, targeting LAG-3, may have similar immune-related toxicities, though specific data is limited. Lenvatinib, a multi-kinase inhibitor, is known for causing hypertension, proteinuria, diarrhea, fatigue, and hand-foot syndrome. These treatments require careful monitoring and management of side effects to ensure patient safety.

What prior FDA approvals exist?

Pembrolizumab, an anti-PD-1 therapy, has been FDA approved for the treatment of NSCLC, often in combination with chemotherapy, as demonstrated in the KEYNOTE-407 trial. Other similar immune checkpoint inhibitors include Nivolumab (anti-PD-1) and Atezolizumab (anti-PD-L1), which have also received FDA approval for NSCLC. Nivolumab is sometimes used in combination with Ipilimumab (anti-CTLA-4), another immune checkpoint inhibitor. Multi-kinase inhibitors like Lenvatinib are being explored in combination therapies but are not yet standard for NSCLC. These approvals highlight the evolving landscape of immunotherapy and targeted treatments in NSCLC.

What other types of research exist?

Promising novel alternatives for NSCLC patients in 2024 include: 1) Ramucirumab (VEGFR2 inhibitor) plus Pembrolizumab, which has shown improved overall survival in patients with progressive disease after initial immunotherapy. 2) Cabozantinib (a multi-kinase inhibitor) with or without Atezolizumab (Anti-PD-L1), which has shown preliminary activity in patients previously treated with immunotherapy. These combinations are currently being evaluated in ongoing phase III trials.

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Monoclonal Antibodies

Pembrolizumab Combo for Lung Cancer

Phase 2

Waitlist Available

Research Sponsored by Merck Sharp & Dohme Corp.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated

Has a histologically- or cytologically-confirmed diagnosis of Stage IV (American Joint Committee on Cancer [AJCC] v 8) NSCLC and has not had prior systemic therapy for advanced disease

Must not have

Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs)

Radiographic evidence of major blood vessel invasion/infiltration

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to ~2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing different combinations of cancer drugs to find the best treatment for patients with advanced lung cancer who haven't been treated before. The drugs help the immune system fight cancer or stop the cancer cells from growing.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include immune-related reactions affecting organs like the liver or lungs, infusion reactions from the drug entering the body, fatigue, digestive issues such as nausea and diarrhea. Each drug also has unique risks that will be monitored throughout the trial.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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My lung cancer is at stage IV and I haven't had systemic therapy for it.

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

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I am fully active or can carry out light work.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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My cancer has spread to major blood vessels.

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

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I have an active tuberculosis infection.

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I have had chemotherapy for my lung cancer that has spread.

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I have been treated with a drug targeting the LAG-3 receptor before.

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I haven't had major heart problems or a stroke in the last year.

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I have received an organ or tissue transplant from another person.

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I have not fully recovered from major surgery or had surgery within the last 3 weeks.

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I have cancer that has spread to my brain or spinal cord.

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I have severe digestive issues that could affect medication absorption.

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I have been treated with specific immune therapy before.

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I have been treated with a drug targeting blood vessel growth in cancer.

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I haven't had any radiotherapy in the last 2 weeks or lung radiation over 30 Gy in the last 6 months.

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I have an immune system disorder or have been on high-dose steroids or other immune-weakening medicines recently.

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I have had or currently have lung inflammation treated with steroids.

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I am currently being treated for an infection with medication.

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I have a history of hepatitis B or active hepatitis C.

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I have fluid buildup in my abdomen or around my lungs.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to ~2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to ~2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to ~2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)

Secondary study objectives

Number of Participants Discontinuing Study Drug Due to AEs

Number of Participants Experiencing Adverse Events (AEs)

Overall Survival (OS)

+1 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

12Treatment groups

Experimental Treatment

Group I: GEP low TMB low: Pembrolizumab + QuavonlimabExperimental Treatment2 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 + LenvatinibExperimental Treatment2 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 + FavezelimabExperimental Treatment2 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 + QuavonlimabExperimental Treatment2 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 + LenvatinibExperimental Treatment2 Interventions

Group VI: GEP low TMB hi: Pembrolizumab + FavezelimabExperimental Treatment2 Interventions

Group VII: GEP hi TMB low: Pembrolizumab + QuavonlimabExperimental Treatment2 Interventions

Group VIII: GEP hi TMB low: Pembrolizumab + LenvatinibExperimental Treatment2 Interventions

Group IX: GEP hi TMB low: Pembrolizumab + FavezelimabExperimental Treatment2 Interventions

Group X: GEP hi TMB hi: Pembrolizumab + QuavonlimabExperimental Treatment2 Interventions

Group XI: GEP hi TMB hi: Pembrolizumab + LenvatinibExperimental Treatment2 Interventions

Group XII: GEP hi TMB hi: Pembrolizumab + FavezelimabExperimental Treatment2 Interventions

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pembrolizumab

2017

Completed Phase 3

~3150

Favezelimab

2016

Completed Phase 1

~490

Quavonlimab

2017

Completed Phase 2

~420

Lenvatinib

2017

Completed Phase 4

~2070

0 / 23Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Non-Small Cell Lung Cancer (NSCLC) include immune checkpoint inhibitors and multi-kinase inhibitors. Pembrolizumab, an anti-PD-1 therapy, works by blocking the PD-1 receptor on T-cells, preventing cancer cells from evading the immune system. Quavonlimab, an anti-CTLA-4 therapy, enhances T-cell activation and proliferation by inhibiting the CTLA-4 checkpoint, which normally downregulates immune responses. Favezelimab targets LAG-3, another immune checkpoint, further boosting T-cell activity against cancer cells. Lenvatinib, a multi-kinase inhibitor, targets multiple pathways involved in tumor growth and angiogenesis. These treatments are crucial for NSCLC patients as they enhance the body's immune response to cancer and inhibit tumor growth, offering potential for improved outcomes.

Effect of ALK-inhibitors in the treatment of non-small cell lung cancer: a systematic review and meta-analysis.