FDA Grants Priority Review to Pembrolizumab for PD-L1-High Subgroup of NSCLC

The Food and Drug Administration (FDA) granted priority review to pembrolizumab (Keytruda) monotherapy for the first-line treatment of patients with locally advanced or metastatic nonsquamous or squamous non-small cell lung cancer (NSCLC) whose tumors express PD-L1 without EGFR or ALK genomic tumor aberrations.

“Pembrolizumab becomes an option for patients who have advanced non-small cell lung cancer and do not have EGFR or ALK mutations, and who do express PD-L1 at least the 1% level,” said lead study author Gilberto Lopes, MD, MBA, a medical oncologist at the Sylvester Comprehensive Cancer Center, University of Miami Health System in Florida, during a presentation at ASCO.

“We do need to do a lot more work. Even though patients do better today, they still do not do well enough. The vast majority of patients with advanced lung cancer will have disease progression and will succumb to lung cancer. So, we need to continue doing more work.”

The new supplemental biologics license application included data from the pivotal Phase III KEYNOTE-042 trial—one of 3 trials designed to demonstrate a significant improvement in OS in patients with NSCLC.

In the trial, those treated with frontline Keytruda lived 4 to 8 months longer than those who received standard of care chemotherapy, depending on their level of PD-L1 expression.

In addition, OS was correlated with greater levels of PD-L1 expression: Tumor proportion score (TPS) ≥50% (20 vs 12.2 months; HR, 0.69; 95% CI, 0.56-0.85; P = .0003), TPS ≥20% (17.7 vs 13.0 months; HR, 0.77; 95% CI, 0.64-0.92; P = .002), and TPS ≥1% (16.7 vs 12.1 months; HR, 0.81; 95% CI, 0.71-0.93; P = .0018) compared with chemotherapy.

Across all patients with PD-L1 TPS of 1% to 49%, which was an exploratory analysis, the median OS was 13.4 months with pembrolizumab compared with 12.1 months for chemotherapy (HR, 0.92; 0.77-1.11).

The FDA set a Prescription Drug User Fee Act (PDUFA) date for Jan. 11, 2019.

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

“We are pleased that the FDA is reviewing this (supplemental biologics license application) 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 added.