An advisory panel on Tuesday voted 10 to 0 that the FDA should hold off deciding on Merck & Co.'s application seeking a wider label for Keytruda (pembrolizumab) in triple-negative breast cancer (TNBC) until the company can supply more data from the Phase III KEYNOTE-522 trial. The vote follows a negative review by FDA staff last week in which they cast doubt on the KEYNOTE-522 findings and indicated that neither the study's design nor its results support approval of the anti-PD-1 therapy in the adjuvant setting for patients with high-risk, early TNBC.
Keytruda received FDA clearance for its first breast cancer indication last November, when the agency granted accelerated approval for use in combination with chemotherapy to treat patients with locally recurrent, unresectable or metastatic TNBC whose tumours express PD-L1 with a combined positive score of 10 or greater. Merck is now looking to broaden the label to include treating patients with high-risk, early-stage TNBC, in combination with chemotherapy in the neoadjuvant setting, then as a single agent as adjuvant treatment after surgery. The FDA has set a target action date of March 29.
Merck noted that the KEYNOTE-522 study had met one of the dual primary endpoints of pathological complete response (pCR). The company had previously reported that significantly more TNBC patients achieved pCR when Keytruda was added to chemotherapy, compared to chemotherapy alone, but FDA reviewers last week pointed to a more recent interim analysis showing only a "small improvement" in pCR that they said was of "questionable clinical meaningfulness."
They also noted that the other main goal of event-free survival (EFS) had not met its pre-specified threshold for statistical significance and remained immature. On Tuesday, Merck said it is continuing to evaluate the EFS endpoint, adding that the next interim analysis is calendar-driven, with data expected in the third quarter of 2021.
Roy Baynes, head of global clinical development at Merck, stated that while the company is "disappointed in the outcome of today's meeting, we believe Keytruda can help meet the significant unmet medical need for these patients." He also said Merck is "confident" in the KEYNOTE-522 results seen to date, including the pCR rates as well as the "encouraging" interim EFS data, and that it will "[continue] to work with the FDA on its review of our application."
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