NCT03516981

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

A Phase 2 Precision Oncology Study of Biomarker-Directed, Pembrolizumab-(MK-3475, SCH 900475) Based Combination Therapy for Advanced Non-Small Cell Lung Cancer (KEYNOTE-495; KeyImPaCT)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 245 (actual)
• Sponsor: Merck Sharp & Dohme LLC · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

After Amendment 5, participants can receive 800 mg of favezelimab every 3 weeks (Q3W)

Conditions

• Advanced Non-Small Cell Lung Cancer

Interventions

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

Timeline

• Start date: 2018-10-01
• Primary completion: 2025-06-13
• Completion: 2025-06-13
• First posted: 2018-05-07
• Last updated: 2025-07-01

Locations

81 sites across 16 countries: United States, Australia, Canada, Hong Kong, Ireland, Italy, Japan, Poland, Russia, Singapore, South Africa, South Korea, Spain, Switzerland, Taiwan, United Kingdom

Regulatory

• FDA-regulated drug study