FDA Grants Priority Review to Keytruda as First-line Therapy for Advanced NSCLC

FDA Grants Priority Review to Keytruda as First-line Therapy for Advanced NSCLC

The U.S. Food and Drug Administration (FDA) has agreed to review Merck‘s application seeking the extension of Keytruda (pembrolizumab) as first-line treatment for patients with advanced non-small cell lung cancer (NSCLC).

The supplemental Biologics License Application (sBLA) was granted priority review and a decision is expected by Jan. 11, 2019. Merck, Keytruda’s developer, is known as MSD outside the United States and Canada.

If approved, Keytruda will be used as a stand-alone treatment for patients with locally advanced or metastatic NSCLC, who have no mutations in the EGFR or ALK genes, and whose tumors have at least 1 percent of cancer cells producing the PD-L1 factor.

“Keytruda is already a foundation for the treatment of metastatic non-small cell lung cancer,” Roy Baynes, MD, said in a press release. Baynes is senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories.

“We are pleased that the FDA is reviewing this sBLA and we look forward to potentially extending the monotherapy indication for Keytruda to locally advanced or metastatic patients whose tumors express PD-L1, with a tumor proportion score of one percent or more,” he said.

The application was based on data from a pivotal Phase 3 trial, KEYNOTE-042 (NCT02220894), in which Keytruda outperformed chemotherapy at extending patients’ lives.

The trial included 1,274 patients with locally advanced or metastatic NSCLC who received either Keytruda, once every three weeks, or standard chemotherapy. The chemo regimen for patients with squamous NSCLC was carboplatin plus Taxol (paclitaxel). For non-squamous NSCLC patients, it was carboplatin plus Alimta (pemetrexed), with an option of adding Alimta as maintenance.

Data presented in June at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting showed that Keytruda significantly extended the lives of patients with PD-L1 expression in their tumors.

The benefits were particularly more evident in patients with 50% or more tumor cells positive for the PD-L1 factor, who had a 31% reduction in their risk of death. But patients where the PD-L1 factor was produced by 20% or more cells or by at least 1% of cells, still saw a reduction in their risk of death by 23% and 19%, respectively.

“KEYNOTE-042 is the first study with a primary end-point [goal] of overall survival to demonstrate superiority of Keytruda over platinum-based chemotherapy in patients with previously untreated advanced/metastatic NSCLC without sensitizing EGFR or ALK alterations and a PD-L1 [score] above 1%,” researchers wrote.

“These data confirm and potentially extend the role of Keytruda monotherapy as a standard first-line treatment for PD-L1-expressing advanced/metastatic NSCLC,” they concluded.

To date, treatment-related side effects were more frequent in the chemotherapy group (41%) than among those receiving Keytruda (17.8%).

The promising safety profile and survival results have led an external committee to recommend that the trial continue, in order to evaluate whether Keytruda also extends the time a patient lives without disease progression.