NEW YORK – Merck said on Friday that, based on updated data from the Phase III KEYNOTE-811 trial, it is working with the US Food and Drug Administration to update the accelerated approval for Keytruda (pembrolizumab) plus Genentech's Herceptin (trastuzumab) and chemotherapy as first-line treatment for advanced HER2-positive gastric cancer.
The update Merck is seeking would limit the indication to HER2-positive gastric or gastroesophageal cancer patients whose tumors express PD-L1.
In 2021, the FDA initially granted the Keytruda, Herceptin, and chemo combination accelerated approval based on response rate data from the Phase III KEYNOTE-811 trial, in which Merck randomized patients to receive either the immunotherapy combination or placebo, Herceptin, and chemo. Merck did not limit patient enrollment to patients with PD-L1-expressing cancers, and accordingly, that FDA approval did not include that biomarker criteria.
Now, however, Merck has reported that a subgroup analysis by PD-L1 expression demonstrates that the progression-free survival benefit on the trial is limited to those whose cancers express PD-L1 with a combined positive score of at least one. More than 80 percent of patients enrolled in the trial did have positive PD-L1 expression, resulting in this biomarker-specific benefit driving the observed benefit in the full intention-to-treat population.
In addition to the discussions Merck is having with the FDA about updating the Keytruda label, the drugmaker says it plans to present the data at an upcoming medical meeting and share them with regulatory authorities worldwide.