The U.S. Food and Drug Administration (FDA) has approved an expanded label for Keytruda, Merck’s anti-PD-1 therapy, as monotherapy for the first-line treatment of patients with stage III non-small cell lung cancer (NSCLC) who are not candidates for surgical resection or definitive chemoradiation, or metastatic NSCLC, and whose tumors express PD-L1 (tumor proportion score [TPS] ≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations. The approval is based on results from the Phase 3 KEYNOTE-042 trial, in which overall survival (OS) was sequentially tested as part of a pre-specified analysis plan. In the trial, Keytruda monotherapy demonstrated a statistically significant improvement in OS compared with chemotherapy alone in patients whose tumors expressed PD-L1 with a TPS ≥50%, with a TPS ≥20%, and then in the entire study population (TPS ≥1%).

"This expanded first-line indication now makes Keytruda monotherapy an option for more patients with non-small cell lung cancer, including those for whom combination therapy may not be appropriate," said Dr. Jonathan Cheng, vice president, oncology clinical research, Merck Research Laboratories.

Immune-mediated adverse reactions, which may be severe or fatal, can occur with Keytruda, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, severe skin reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation (HSCT). Based on the severity of the adverse reaction, Keytruda should be withheld or discontinued and corticosteroids administered if appropriate. Keytruda can also cause severe or life-threatening infusion-related reactions. Based on its mechanism of action, Keytruda can cause fetal harm when administered to a pregnant woman. For more information, see "Selected Important Safety Information" below.

"The KEYNOTE-042 trial demonstrated a survival benefit with Keytruda monotherapy across histologies in certain patients with stage III or metastatic non-small cell lung cancer whose tumors expressed PD-L1 in at least 1% of tumor cells," said Dr. Gilberto Lopes, associate director for global oncology at the Sylvester Comprehensive Cancer Center at the University of Miami. "As a practicing oncologist, having additional options available for patients is important in the rapidly evolving treatment landscape for lung cancer, which remains the leading cause of cancer death in the United States."

Keytruda was the first anti-PD-1 therapy in metastatic NSCLC approved in the first-line setting as combination therapy or monotherapy.

About KEYNOTE-042

The approval was based on data from the KEYNOTE-042 trial, a randomized, multi-center, open-label, active-controlled trial in patients with stage III NSCLC who were not candidates for surgical resection or definitive chemoradiation, or metastatic NSCLC, and whose tumors expressed PD-L1 (TPS ≥1%) and who had not received prior systemic treatment for metastatic NSCLC. Patients with EGFR or ALK genomic tumor aberrations; autoimmune disease that required systemic therapy within two years of treatment; a medical condition that required immunosuppression; or who had received more than 30 Gy of radiation in the thoracic region within 26 weeks prior to initiation of study treatment were ineligible.

The study enrolled 1,274 patients who were randomized (1:1) to receive Keytruda 200 mg intravenously every three weeks (n=637) or investigator’s choice of either of the following chemotherapy regimens (n=637):

Pemetrexed 500 mg/m2 every three weeks and carboplatin AUC 5 to 6 mg/mL/min every three weeks on Day 1 for a maximum of six cycles followed by optional pemetrexed 500 mg/m2 every three weeks for patients with nonsquamous histologies; or

Paclitaxel 200 mg/m2 every three weeks and carboplatin AUC 5 to 6 mg/mL/min every three weeks on Day 1 for a maximum of six cycles followed by optional pemetrexed 500 mg/m2 every three weeks for patients with nonsquamous histologies

Treatment with Keytruda continued until RECIST v1.1 (modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ)-defined progression of disease, unacceptable toxicity, or a maximum of 24 months. The main efficacy outcome measure was OS in the subgroup of patients with TPS ≥50% NSCLC, the subgroup of patients with TPS ≥20% NSCLC, and the overall population with TPS ≥1% NSCLC. Additional efficacy outcome measures were progression-free survival (PFS) and overall response rate (ORR) in the subgroup of patients with TPS ≥50% NSCLC, the subgroup of patients with TPS ≥20% NSCLC, and the overall population with TPS ≥1% NSCLC as assessed by a blinded independent central radiologists’ (BICR) review according to RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of five target lesions per organ.

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