FDA Grants Priority Review for Pembrolizumab, Chemotherapy Combination in NSCLC

The FDA has granted priority review to Merck’s supplemental Biologics License Application (BLA) for pembrolizumab (Keytruda) in combination with pemetrexed (Alimta) and platinum chemotherapy as first-line treatment for patients with metastatic nonsquamous non—small cell lung cancer (NSCLC), Merck announced today.

The Prescription Drug User Fee Act date has been set for September 23. The FDA’s acceptance of the application is based on overall survival (OS) and progression-free survival (PFS) data from the phase 3 KEYNOTE-189 trial. The trial is the confirmatory trial for KEYNOTE-021, a phase 2 study that led to pembrolizumab being the first FDA-approved anti-PD-1 therapy in combination with chemotherapy for the first-line treatment of patients with metastatic nonsquamous NSCLC, regardless of PD-L1 expression.

In the double-blind, phase 3 KEYNOTE-189 trial¹, 616 patients with NSCLC without EGFR or ALK mutations who had no previous treatment were randomized 2:1 to receive pemetrexed and a platinum-based drug plus either 200 mg of pembrolizumab or placebo every 3 weeks for 4 cycles, followed by pembrolizumab or placebo for up to 35 cycles plus pemetrexed matienance therapy.

After a median follow-up of 10.5 months, the estimated rate of OS at 12 months was 69.2% in the pembrolizumab cohort, compared to 49.4% in the placebo cohort. Median PFS in the pembrolizumab cohort (8.8 months) was nearly double that of the placebo cohort (4.9 months).

“Keytruda is the first immunotherapy to significantly extend survival of patients with NSCLC in combination with chemotherapy as a first-line treatment, including in patients whose tumors are either PD-L1 negative or are untested,” said Roger M. Perlmutter, MD, president, Merck Research Laboratories, in a statement.

If approved by the FDA, this would represent the third indication for pembrolizumab in metastatic NSCLC in the United States based on OS data.

Earlier this month, pembrolizumab monotherapy as first-line treatment in locally advanced or metastatic NSCLC met its primary endpoint of overall survival in the phase 3 KEYNOTE-042 trial when compared to platinum-based chemotherapy.

Outside of NSCLC, the anti-PD-1 therapy currently has indications for melanoma, head and neck cancer, classical Hodgkin lymphoma, urothelial carcinoma, and gastric cancer. In March, the FDA accepted a new supplemental BLA and granted Priority Review for pembrolizumab as treatment for advanced cervical cancer, which marked the first filing acceptance and Priority Review granted for an anti-PD-1 therapy in cervical cancer.

Reference:

1. Gandhi L, Rodriguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. [published online April 16, 2018]. N Engl J Med. doi: 10.1056/NEJMoa1801005.