At a glance
ClinicalIndex Comparison Record- ✓Histologically or cytologically confirmed Stage IV NSCLC (AJCC v8) with no prior systemic therapy for advanced disease
- ✓Documented absence of EGFR mutations, ALK rearrangement, ROS1 rearrangement, and BRAF mutations
- ✓Measurable disease per RECIST 1.1
- ✓Archival tumor tissue or newly obtained core/excisional biopsy from non-irradiated lesion
- ✕Significant cardiovascular impairment within 12 months: NYHA Class III+ heart failure, unstable angina, MI, CVA, hemodynamically unstable arrhythmia, or LVEF below institutional normal
- ✕QTc prolongation >480 ms
- ✕Symptomatic ascites or pleural effusion
- ✕Prior allogeneic tissue or solid organ transplant
Standardized by ClinicalIndex from the ClinicalTrials.gov record · verify against the source.
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)
In Brief
A Phase 2 clinical trial evaluating Pembrolizumab, Favezelimab, and 2 other interventions for Advanced Non-Small Cell Lung Cancer. Completed, enrolled 245 participants across 81 sites in 16 countries.
Signals
Detailed 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.
Study Details
Timeline
Arms & Interventions
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.
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).
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).
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).
Interventions
200 mg pembrolizumab solution for intravenous (IV) infusion administered Q3W
200 mg or 800 mg favezelimab solution for IV infusion administered Q3W
20 mg lenvatinib capsules administered orally once daily
Quavonlimab solution for IV infusion administered at the RP2D (dose and schedule based on study NCT03179436)