Phase III KEYNOTE-407 trial of Keytruda in combination with chemotherapy leads to first line EU approval for NSCLC

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

Data Supporting the European Approval- The approval was based on data from KEYNOTE-407, a Phase III, 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 (PFS); secondary endpoints include objective response rate (ORR) and duration of response (DOR). The study enrolled 559 patients who were randomized (1:1) 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 percent compared to chemotherapy alone (HR=0.64 [95% CI, 0.49-0.85]; p<0.0008). The Keytruda combination also demonstrated improved PFS, with a reduction in the risk of progression or death of 44 percent compared to chemotherapy alone (HR=0.56 [95% CI, 0.45-0.70]; p<0.0001). Among patients who received the Keytruda combination, the ORR was 58 percent (95% CI, 52-64) compared to 38 percent (95% CI, 33-44) for patients who received chemotherapy alone (p<0.0001). The median DOR was 7.7 months (range, 1.1+ to 14.7+ months) for patients who received the Keytruda combination compared to 4.8 months (range, 1.3+ to 15.8+ months) for patients who received chemotherapy alone.

The safety of Keytruda in combination with chemotherapy has been evaluated in 791 patients with NSCLC receiving 200 mg, 2 mg/kg or 10 mg/kg Keytruda every three weeks, in clinical studies. In this patient population, the most frequent adverse reactions were nausea (49%), anemia (48%), fatigue (38%), constipation (34%), diarrhea (31%), neutropenia (29%), and decreased appetite (28%). Incidences of Grade 3-5 adverse reactions were 67 percent for the Keytruda combination and 66 percent for chemotherapy alone.