MSD announced on May 23 that a key Phase III study of Keytruda (pembrolizumab) combined with chemotherapy (carboplatin + paclitaxel or naproxen + paclitaxel) for the first-line treatment of metastatic squamous NSCLC achieved overall survival (OS) and progression-free survival ( The two primary endpoints of PFS).
The results of an interim analysis conducted by an independent data monitoring committee showed that Keytruda combined with chemotherapy was significantly more effective in treating OS and PFS than chemotherapy alone. Keytruda’s safety in this combination therapy is consistent with that previously observed in lung cancer. Specific data for KEYNOTE-407 will be released at the 2018 ASCO Annual Meeting.
KEYNOTE-407 (NCT02775435) is a randomized, double-blind, placebo-controlled phase III clinical study evaluating Keytruda combined with chemotherapy (carboplatin + paclitaxel or naproxen + paclitaxel) with chemotherapy alone (carboplatin + paclitaxel or Naproxen + paclitaxel) efficacy. The study included 560 untreated metastatic squamous NSCLC patients who had not received systemic treatment for advanced disease.
The two primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints include objective response rate (ORR) and duration of remission (DOR).
So far, five phase III clinical trials have confirmed the improvement of survival of Keytruda in advanced non-small cell lung cancer. Merck also announced that it has submitted to the FDA a biologics supplemental application (SBLA) for Keytruda combined with chemotherapy (carboplatin + paclitaxel or naproxen + paclitaxel) for the first-line treatment of metastatic squamous cell non-small cell lung cancer.
The FDA has previously approved Keytruda twice as the first-line therapy for NSCLC. They are: 1) single-agent (200 mg once every 3 weeks) first-line treatment with PD-L1 expression levels ≥ 50% and non-EGFR or ALK mutations Small cell lung cancer (NSCLC) until disease progression, intolerable toxicity, or 24 months disease progression. 2) First-line treatment of metastatic non-squamous NSCLC with combination chemotherapy (pemetrexed + carboplatin). These two approvals are based primarily on ORR and PFS data from KEYNOTE-024 and KEYNOTE-021 studies.
On January 16, Merck announced positive results for key phase III KEYNOTE-189 study of Keytruda + pemetrexed + cisplatin or carboplatin for first-line metastatic non-squamous non-small cell lung cancer (NSCLC) compared to Pemetrex The plug-and-platinum chemotherapy group significantly improved overall survival (OS) and progression-free survival (PFS), reaching a composite end point. Keytruda combined with chemotherapy became the first PD-1 combination therapy to show an improvement in the overall survival of NSCLC.
On April 9, Merck announced that Keytruda compared with platinum-based chemotherapy (carboplatin + paclitaxel or carboplatin + pemetrexed) significantly prolongs the overall survival of patients with positive PD-L1 expression (TPS ≥ 1%) (OS) . Analysis of patients with higher levels of PD-L1 (TPS ≥ 50% or ≥ 20%) also found that OS was significantly longer.