Trial results for a Phase 2 study investigating pembrolizumab (Keytruda) in combination with quavonlimab, favezelimab, or lenvatinib for advanced non-small cell lung cancer (NSCLC) were posted on ClinicalTrials.gov on 2026-06-08. The study, which used biomarker-directed patient triage, reported Objective Response Rates (ORR) ranging from 0.0% to 60.0% across different biomarker groups and combination therapies.
Background
The study investigated pembrolizumab, a widely used cancer therapy, in combination with investigational agents quavonlimab, favezelimab, or lenvatinib. The focus was on participants with advanced non-small cell lung cancer (NSCLC) who had not received prior systemic therapy, utilizing a biomarker-based triage approach to guide treatment selection.
Trial design
The completed Phase 2 study (NCT03516981), known as MK-3475-495/KEYNOTE-495, enrolled 245 participants with advanced non-small cell lung cancer (NSCLC) without prior systemic therapy. The study investigated the utility of biomarker-based triage, using gene expression profile (GEP) and tumor mutational burden (TMB), to assign participants to different treatment arms. Participants within these biomarker-defined groups were randomized to receive pembrolizumab in combination with quavonlimab, favezelimab, or lenvatinib. A primary hypothesis of the study was to evaluate the Objective Response Rate (ORR) in these combination therapies.
Key results
The trial reported Objective Response Rates (ORR) across various biomarker-defined subgroups:
- For Pembrolizumab + Lenvatinib:
- GEP Low / TMB Low: 12.0%
- GEP Low / TMB High: 33.3%
- GEP High / TMB Low: 40.9%
- GEP High / TMB High: 57.1%
- For Pembrolizumab + Quavonlimab:
- GEP Low / TMB Low: 11.5%
- GEP Low / TMB High: 30.8%
- GEP High / TMB Low: 13.6%
- GEP High / TMB High: 52.4%
- For Pembrolizumab + Favezelimab 200 mg:
- GEP Low / TMB Low: 0.0%
- GEP Low / TMB High: 33.3%
- GEP High / TMB Low: 25.0%
- GEP High / TMB High: 60.0%
What this means
The results from this Phase 2 study suggest that Objective Response Rates in advanced non-small cell lung cancer vary considerably based on biomarker status (gene expression profile and tumor mutational burden) and the specific pembrolizumab-based combination therapy used. The highest ORR was observed in the Pembrolizumab + Favezelimab 200 mg arm for participants with GEP High / TMB High status, reaching 60.0%. Conversely, the lowest ORR was 0.0% in the Pembrolizumab + Favezelimab 200 mg arm for participants with GEP Low / TMB Low status. These findings underscore the potential utility of biomarker-directed treatment strategies to optimize outcomes in advanced NSCLC, indicating that certain patient subgroups may benefit more from specific combination regimens.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for the study NCT03516981, titled "A Study of Biomarker-Directed, Pembrolizumab (MK-3475) Based Combination Therapy for Advanced Non-Small Cell Lung Cancer (MK-3475-495/KEYNOTE-495)", were posted on 2026-06-08 on clinicaltrials.gov.