Roger M. Perlmutter
The phase 3 KEYNOTE-042 trial of pembrolizumab met its primary endpoint of OS for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer with PD-L1 expression, according to the agent’s manufacturer.
Pembrolizumab (Keytruda, Merck) is an anti-PD-1 therapy approved for the treatment of several cancer types, including as first-line treatment for patients with metastatic NSCLC with high PD-L1 expression, and for patients with metastatic NSCLC following disease progression on chemotherapy.
KEYNOTE-042 is an international, randomized, open-label phase 3 trial of first-line monotherapy pembrolizumab compared with carboplatin plus paclitaxel or carboplatin plus pemetrexed in 1,274 patients with PD-L1-positive NSCLC.
All patients had tumor proportion scores of at least 1% — indicating high PD-L1 expression —and were stratified based on their tumor proportion score. Patients also had no EGFR or ALK genomic tumor aberrations and had not previously received systemic therapy for advanced disease.
An interim analysis conducted by an independent monitoring committee showed treatment with pembrolizumab resulted in significantly longer OS compared with treatment with platinum-based chemotherapy.
OS improved among patients with a tumor proportion scores of at least 50%, scores of at least 20% and the entire population with scores of at least 1%.
“Improvement in OS 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 OS as the primary endpoint that has demonstrated significant benefit as first-line therapy in NSCLC patients who tested positive for PD-L1 at 1% or higher,” Tony Mok, MD, professor in the department of clinical oncology at the Chinese University of Hong Kong, said in a company-issued press release.
The safety profile of pembrolizumab appeared consistent with that observed in previous monotherapy studies of patients with advanced NSCLC.
The independent committee recommend the trial continue to assess PFS, a predefined secondary endpoint.
“With KEYNOTE-042, Keytruda 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% or higher by tumor proportion score,” Roger M. Perlmutter, MD, PhD, president of Merck Research Laboratories, said in the release. “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.”
Results from KEYNOTE-042 will be presented at an upcoming meeting and submitted to regulatory authorities, according to the press release.