Merck’s KEYTRUDA monotherapy trial meets primary endpoint

Treatment with KEYTRUDA resulted in significantly longer OS than platinum-based chemotherapy in patients with a PD-L1 tumour proportion score of ≥1 percent

Merck announced that the pivotal Phase 3 KEYNOTE-042 trial evaluating KEYTRUDA, Merck’s anti-PD-1 therapy, as monotherapy for the first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC, including nonsquamous or squamous histologies) met its primary endpoint of overall survival (OS). An interim analysis conducted by the independent Data Monitoring Committee (DMC) demonstrated that treatment with KEYTRUDA 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 per cent. As part of a pre-specified analysis plan, OS was sequentially tested and was significantly improved in patients with a TPS of ≥50 per cent, with a TPS of ≥20 per cent and then in the entire study population with a TPS of ≥1 per cent. The safety profile of KEYTRUDA in this trial was consistent with that observed in previously reported monotherapy studies involving patients with advanced NSCLC.

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, 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 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.”

“Improvement in overall survival is the ultimate objective in the treatment of advanced lung cancer. KEYNOTE-042 is the first randomised 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 per cent or higher,” said Dr Tony Mok, professor in the Department of Clinical Oncology at the Chinese University of Hong Kong.

Merck has an extensive clinical development program in lung cancer and is advancing multiple registration-enabling studies with KEYTRUDA in combination with other treatments and as monotherapy. The programme, which is consists of nearly 9,000 patients across 15 clinical studies, is evaluating KEYTRUDA across multiple settings and stages of the disease.