FDA Accepts Expanded Indication Application for Keytruda

The FDA has accepted a supplemental new Biologics License Application (sBLA) for pembrolizumab (Keytruda), an anti-PD-1 therapy for treating patients with advanced non-small cell lung cancer (NSCLC).

The application seeks an expanded indication for the drug as a treatment for patients with advanced non—small cell lung cancer (NSCLC) with PD-L1 expression on ≥1% of tumors cells.

The sBLA follows a phase 2/3 trial that evaluated the efficiency of Keytruda compared with chemotherapy based on the measurement of tumors that expressed PD-L1 in patients with NSCLC that were previously treated.

Keytruda showed an improvement in overall survival (OS) compared with chemotherapy in patients with NSCLC. The application provides supporting evidence to convert the accelerated approval granted to Keytruda in October 2015 to a full indication.

Furthermore, the new data could reduce the PD-L1 expression threshold to ≥1% of cells.

“The data from KEYNOTE-010 demonstrated an overall survival benefit in patients with PD-L1 expression on one percent or more of the cancer cells,” said Senior Vice President of Merck Research Laboratories, Roger Dansey, MD. “We look forward to working with the FDA over the course of the application review process and remain committed to advancing our broad clinical program for cancers where patients are in need of new options, including lung cancer.”

Improving Lung Cancer Survival

All patients enrolled in the trial had progression on at least 2 cycles of a previous platinum chemotherapy. The primary endpoints were OS and progression-free survival (PFS) in the full population and those with PD-L1 expression on more than 50% of tumor cells.

Median OS was 10.4 months with the dose of 2 mg/kg of Keytruda compared with 8.5 months with docetaxel in those with >1% PD-L1 expressing NSCLC (HR, 0.71; 95% CI, 0.58-0.88; P = .0008).

The larger dose of Keytruda (10 mg/kg) showed median OS of 12.7 months, representing a 39% reduction in the risk of death versus docetaxel (HR, 0.61; 95% CI, 0.49-0.75; P <.0001).

A median follow-up of 13.1 months showed an estimated 1-year OS rate of 43.2% and 52.3% for the 2 mg/kg and 10 mg/kg doses, respectively. The 1-year OS rate with docetaxel was 34.6%.

In patients with ≥50% PD-L1 expression, median OS with the 2 mg/kg dose of Keytruda was 14.9 months compared with 8.2 months in docetaxel (HR, 0.54; 95% CI, 0.38-0.77; P = .0002). In the 10 mg/kg arm, the median OS was 17.3 months, representing a 50% improvement over docetaxel (HR, 0.50; 95% CI, 0.36-0.70; P <.0001).

Median PFS was not significantly improved with Keytruda in those with >1% PD-L1 expression, possibly as a result of pseudoprogression. In this cohort, median PFS was 3.9 months with the 2 mg/kg dose of Keytruda versus 4.0 months with docetaxel (HR, 0.88; 95% CI, 0.74-1.05; P = .07). For the 10 mg/kg dose of Keytruda, median PFS was 4.0 months (HR vs docetaxel, 0.79; 95% CI, 0.66-0.94; P = .004). The P value for significance was set as <.001.

Currently, under accelerated approval, the improvement in survival and disease related symptoms is still unestablished. Approval for this indication could be based on verification of clinical benefit in the trials.