NEW YORK – The US Food and Drug Administration on Tuesday limited the indication for Merck's checkpoint inhibitor Keytruda (pembrolizumab) when given with Genentech's HER2-targeted drug Herceptin (trastuzumab) and chemotherapy to patients with PD-L1-expressing HER2-positive advanced gastric cancer.
The FDA granted accelerated approval to the combination in 2021 as a first-line treatment for patients with locally advanced, metastatic, HER2-positive gastric or gastroesophageal junction cancer, regardless of PD-L1 expression status. That decision was based on data from the Phase III KEYNOTE-811 trial, which showed a 74 percent response rate for patients on the Keytruda-Herceptin-chemo regimen versus 52 percent for those in the placebo arm.
The updated indication now specifies that patients' tumors must express PD-L1 with a combined positive score of at least one, as determined by an FDA-approved test. The FDA simultaneously approved Agilent's PD-L1 IHC 22C3 pharmDx assay as a companion diagnostic to determine PD-L1 expression for Keytruda eligibility.
The decision to limit the population in this setting is based on an updated analysis from the same KEYNOTE-811 trial, which showed that patients with PD-L1-expressing cancers derived the most benefit from the Keytruda-Herceptin-chemo combination. In contrast, patients whose cancers did not express PD-L1 derived no additional benefit from adding Keytruda to Herceptin and chemo.
This past summer, based on the updated biomarker analysis, Merck requested this label update from the FDA.
European regulators also recently approved the combination for the biomarker-limited group of gastric cancer patients.
In announcing the update, the FDA specified that this combination treatment is still available under accelerated approval and, as such, Merck will still have to provide data confirming the Keytruda-Herceptin-chemo regimen's efficacy and safety.