Merck (MRK), known as MSD outside the United States and Canada, today 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 tumor 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 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 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.

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 program, which is comprised of nearly 9,000 patients across 15 clinical studies, is evaluating KEYTRUDA across multiple settings and stages of the disease.

About KEYNOTE-042

KEYNOTE-042 is an international, randomized, open-label Phase 3 study (ClinicalTrials.gov, NCT02220894) investigating KEYTRUDA 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 tumor 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 KEYTRUDA (200 mg fixed dose every three weeks) as monotherapy or investigator's choice of platinum-based chemotherapy as follows:

carboplatin AUC 5 or 6 mg/mL/min plus paclitaxel 200 mg/m2 every three weeks (Q3W) for a maximum of six cycles for patients with squamous NSCLC; or
carboplatin AUC 5 or 6 mg/mL/min plus pemetrexed 500 mg/m2 Q3W for a maximum of six cycles, followed by optional pemetrexed 500 mg/m2 for patients with nonsquamous NSCLC.
About Lung Cancer

Lung cancer, which forms in the tissues of the lungs, usually within cells lining the air passages, is the leading cause of cancer death worldwide. Each year, more people die of lung cancer than die of colon, breast and prostate cancers combined. The two main types of lung cancer are non-small cell and small cell. NSCLC is the most common type of lung cancer, accounting for about 85 percent of all cases. The five-year survival rate for patients diagnosed in the United States with any stage of lung cancer is estimated to be 18 percent.

About KEYTRUDA® (pembrolizumab) Injection 100mg

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.