Results from the pivotal Phase 3 KEYNOTE-042 trial evaluating pembrolizumab as monotherapy for the first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC, including nonsquamous or squamous histologies) released today show the trial met its primary endpoint of overall survival (OS).
An interim analysis conducted by the independent Data Monitoring Committee (DMC) demonstrated that treatment with pembrolizumab resulted in significantly longer OS than platinum-based chemotherapy (carboplatin plus paclitaxel or carboplatin plus pemetrexed) in patients with a PD-L1 tumour proportion score (TPS) of ≥1 percent.
As part of a pre-specified analysis plan, OS was sequentially tested and was significantly improved in patients with a TPS of ≥50 percent, with a TPS of ≥20 percent and then in the entire study population with a TPS of ≥1 percent.
The safety profile of pembrolizumab in this trial was consistent with that observed in previously reported monotherapy studies involving patients with advanced NSCLC.
KEYNOTE-042 is an international, randomized, open-label Phase 3 study (ClinicalTrials.gov, NCT02220894) investigating pembrolizumab monotherapy compared to standard of care platinum-based chemotherapy in patients with locally advanced or metastatic PD-L1 positive (TPS ≥1%) NSCLC.
Patients had no EGFR or ALK genomic tumour aberrations and had not previously received systemic therapy for advanced disease.
The primary endpoint is OS with TPS of ≥50 percent, ≥20 percent and ≥1 percent, which were assessed sequentially.
The secondary endpoints are PFS and objective response rate (ORR).
The study enrolled 1,274 patients randomized 1:1 to receive either pembrolizumab (200 mg fixed dose every three weeks) as monotherapy or investigator's choice of platinum-based chemotherapy as follows:
“Improvement in overall survival is the ultimate objective in the treatment of advanced lung cancer. KEYNOTE-042 is the first randomized Phase 3 study of a single-agent immunotherapy using overall survival as the primary endpoint that has demonstrated significant benefit as first-line therapy in NSCLC patients who tested positive for PD-L1 at 1 percent or higher,” said Dr. Tony Mok, professor in the Department of Clinical Oncology at the Chinese University of Hong Kong.
Based on the recommendation of the DMC, the trial will continue to evaluate progression-free survival (PFS), which is a secondary endpoint.
Results from KEYNOTE-042 will be presented at an upcoming medical meeting and submitted to regulatory authorities worldwide.
“With KEYNOTE-042, pembrolizumab has now shown a significant survival benefit compared with chemotherapy for patients with locally advanced or metastatic nonsquamous or squamous NSCLC expressing PD-L1 at 1 percent or higher by tumor proportion score,” said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. “KEYTRUDA is a foundational treatment for NSCLC and has consistently demonstrated a survival benefit as monotherapy, or in combination with chemotherapy, in the treatment of metastatic lung cancer. We sincerely thank the patients and clinical investigators for their participation in this important study.”