Data from the late-stage KEYNOTE-024 trial showed that Merck & Co.'s Keytruda (pembrolizumab) was superior to standard chemotherapy for both the primary endpoint of progression-free survival (PFS) and the secondary goal of overall survival (OS) in patients with previously untreated, advanced non-small-cell lung cancer (NSCLC) whose tumours expressed high PD-L1 levels, the company announced Thursday. Based on the results, an independent data monitoring committee recommended that the trial be stopped and that patients in the chemotherapy arm of the study have the opportunity to receive Keytruda.
Roger Perlmutter, president of Merck Research Laboratories, suggested the KEYNOTE-024 data "have the potential to change the therapeutic paradigm in first-line treatment of NSCLC." While Merck did not disclose the magnitude of the benefit seen with Keytruda in the study, it said the findings were sufficient to support regulatory submissions for expanded approval in the US and Europe.
The study enrolled 305 patients with treatment-naïve advanced NSCLC and high levels of the PD-L1 protein, defined as a tumour proportion score of at least 50 percent, who were randomised to receive Keytruda monotherapy or standard platinum-based chemotherapeutic regimens. In addition to the respective primary and secondary endpoints of PFS and OS, the other secondary objective in the study was overall response rate. Merck noted that the safety profile of Keytruda in KEYNOTE-024, whose results will be presented at a future research conference, "was consistent with that observed in previously reported studies in patients with advanced NSCLC."
The drug's label was broadened last October in the US, where it was already approved for melanoma, to include patients with PD-L1-positive NSCLC whose disease progressed after prior treatment. In December, The Lancet published data from the Phase II/III KEYNOTE-010 trial showing that Keytruda prolonged OS in previously-treated NSCLC patients whose tumours expressed any level of PD-L1.
Evercore ISI analyst Mark Schoenebaum suggested Merck intends to pursue a label expansion for Keytruda soon to include a first-line indication for NSCLC. Meanwhile, Bristol-Myers Squibb is testing its PD-1 inhibitor Opdivo (nivolumab) for use as first-line monotherapy in a study that includes lung cancer patients with various levels of PD-L1 expression, with results anticipated in the third quarter. Schoenebaum estimated that since high expressors of PD-L1 only comprise 25 percent to 30 percent of the total NSCLC population, a successful study could result in a significantly expanded label.
For related analysis, see ViewPoints: Here we go again; Merck finishes first but will Bristol-Myers Squibb have the final word? See also ViewPoints: ASCO – Jury remains out on most effective IO combo approach in first-line non-small-cell lung cancer.
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