15 March 2019 - - The European Commission has approved Keytruda, US-based biopharmaceutical company Merck's (NYSE: MRK) anti-PD-1 therapy, in combination with carboplatin and either paclitaxel or nab-paclitaxel, for the first-line treatment of adults with metastatic squamous non-small cell lung cancer (NSCLC), the company said.

This approval is based on data from the Phase 3 KEYNOTE-407 trial, which demonstrated that Keytruda in combination with chemotherapy significantly improved overall survival in adults with metastatic squamous NSCLC regardless of PD-L1 tumor expression status, reducing the risk of death by 36% compared to chemotherapy alone (HR=0.64 [95% CI, 0.49-0.85]; p=0.0008).

This approval allows marketing of the Keytruda combination in all 28 EU member states plus Iceland, Lichtenstein and Norway, at the approved dose of 200 mg every three weeks until disease progression or unacceptable toxicity.

In NSCLC, Keytruda is also approved in Europe for the first-line treatment of metastatic nonsquamous NSCLC in combination with pemetrexed and platinum chemotherapy in adults whose tumors have no EGFR or ALK positive mutations (KEYNOTE-189); First-line treatment of metastatic squamous or nonsquamous NSCLC as monotherapy in adults whose tumors have high PD-L1 expression (tumor proportion score [TPS] ≥50%) with no EGFR or ALK positive tumor mutations (KEYNOTE-024); and Treatment of locally advanced or metastatic NSCLC in adults whose tumors express PD-L1 (TPS ≥1%) and who have received at least one prior chemotherapy regimen (KEYNOTE-010).

The approval was based on data from KEYNOTE-407, a Phase 3, randomized, double-blind, multicenter, placebo-controlled study evaluating Keytruda in combination with carboplatin-paclitaxel or nab-paclitaxel compared with carboplatin-paclitaxel or nab-paclitaxel alone.

The dual primary endpoints are OS and progression-free survival ; secondary endpoints include objective response rate and duration of response.

The study enrolled 559 patients who were randomised to receive one of the following treatments via intravenous infusion:

Keytruda 200 mg and carboplatin AUC 6 mg/mL/min on Day 1 of each 21-day cycle for four cycles and paclitaxel 200 mg/m2 on Day 1 of each 21-day cycle for four cycles or nab-paclitaxel 100 mg/m2 on Days 1, 8 and 15 of each 21-day cycle for four cycles, followed by Keytruda 200 mg every three weeks. Keytruda was administered prior to chemotherapy on Day 1.

Placebo and carboplatin AUC 6 mg/mL/min on Day 1 of each 21-day cycle for four cycles and paclitaxel 200 mg/m2 on Day 1 of each 21-day cycle for four cycles or nab-paclitaxel 100 mg/m2 on Days 1, 8 and 15 of each 21-day cycle for four cycles, followed by placebo every 3 weeks.

In KEYNOTE-407, Keytruda in combination with carboplatin and either paclitaxel or nab-paclitaxel significantly improved OS, reducing the risk of death by 36% compared to chemotherapy alone (HR=0.64 [95% CI, 0.49-0.85]; p