Phase III trial of Keytruda meets endpoint as monotherapy but not combination therapy

Merck Inc announced topline findings from the final analysis of the pivotal Phase III KEYNOTE-062 trial evaluating Keytruda, Merck’s anti-PD-1 therapy, as monotherapy and in combination with chemotherapy (cisplatin and either 5-fluorouracil or capecitabine) for the first-line treatment of advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. In the monotherapy arm of the study, Keytruda met a primary endpoint by demonstrating noninferiority to chemotherapy, the current standard of care, for overall survival (OS) in the entire intention-to-treat (ITT) population of patients whose tumors expressed PD-L1 (Combined Positive Score [CPS] at least 1). In the combination arm of KEYNOTE-062, Keytruda plus chemotherapy was not found to be superior for OS (CPS at least 1 or CPS at elast 10) or progression-free survival (PFS) (CPS at least 1) compared with chemotherapy alone. The safety profile of Keytruda was consistent with that previously observed in gastric cancer. Results will be presented during an oral session at the 55th Annual Meeting of the American Society of Clinical Oncology (ASCO).

Comment: In September 2017, the FDA approved Keytruda as a third-line treatment for previously treated patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction cancer whose tumors express PD-L1 (CPS at least 1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. KEYNOTE-062 is a potential confirmatory trial for this accelerated, third-line approval. In addition to KEYNOTE-062, additional first-line, Phase III studies in Merck’s gastric clinical program include KEYNOTE-811 and KEYNOTE-859, as well as KEYNOTE-585 in the neoadjuvant and adjuvant treatment setting.