A Study of Biomarker-Directed, Pembrolizumab (MK-3475) Based Combination Therapy for Advanced Non-Small Cell Lung Cancer (MK-3475-495/KEYNOTE-495)

Conditions

• Advanced Non-Small Cell Lung Cancer

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Pembrolizumab — BIOLOGICAL
  200 mg pembrolizumab solution for intravenous (IV) infusion administered Q3W
• Favezelimab — BIOLOGICAL
  200 mg or 800 mg favezelimab solution for IV infusion administered Q3W
• Lenvatinib — DRUG
  20 mg lenvatinib capsules administered orally once daily
• Quavonlimab — DRUG
  Quavonlimab solution for IV infusion administered at the RP2D (dose and schedule based on study NCT03179436)

Study Details

This study will investigate the utility of biomarker-based triage for study participants with advanced non-small cell lung cancer (NSCLC) without prior systemic therapy. Study participants within groups defined by a biomarker-based classifier (gene expression profile \[GEP\] and tumor mutational burden \[TMB\]) will be randomized to receive pembrolizumab in combination with quavonlimab (MK-1308), favezelimab (MK-4280), or lenvatinib. The primary hypotheses are as follows: In participants receiving pembrolizumab in combination with either quavonlimab, favezelimab, or lenvatinib, the Objective Response Rate (ORR) will be 1) greater than 5% among participants with low GEP and low TMB, 2) greater than 20% among participants with low GEP and high TMB, 3) greater than 20% among participants with high GEP and low TMB, and 4) greater than 45% among participants with high GEP and high TMB.

Key Dates

Start date

Oct 1, 2018

Status verified

May 2026

Primary completion

Jun 13, 2025

Completion

Jun 13, 2025

Study Design

Enrollment

245 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Pembrolizumab + Lenvatinib
  Participants received pembrolizumab 200 mg every 3 weeks (Q3W) intravenously (IV) plus lenvatinib 20 mg orally 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.
• Experimental: Pembrolizumab + Quavonlimab
  Participants received pembrolizumab 200 mg Q3W IV plus quavonlimab 25 mg every 6 weeks (Q6W) IV until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years).
• Experimental: Pembrolizumab + Favezelimab 200 mg
  Participants received pembrolizumab 200 mg Q3W IV plus favezelimab 200 mg Q3W IV until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years).
• Experimental: Pembrolizumab + Favezelimab 800 mg
  Participants received pembrolizumab 200 mg Q3W IV plus favezelimab 800 mg Q3W IV until disease progression, or until the participant has received 35 administrations of pembrolizumab (approximately 2 years).

Primary Outcome Measure

Objective Response Rate (ORR) [ Time Frame: Up to approximately 80 months ]

Locations (19)

Related coverage on Hipa.ai

• Pembrolizumab Combinations Show Varied ORR in Biomarker-Directed Advanced NSCLC
  Pembrolizumab · Jun 8, 2026 · ClinicalTrials.gov

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