- Merck & Co. on Friday disclosed a study testing its checkpoint inhibitor Keytruda as a second-line treatment for advanced gastric cancer failed to show a survival benefit, denting the New Jersey pharma's plans for expanding use of the drug in that patient population.
- News of the trial miss comes only three months after the Food and Drug Administration approved Keytruda as a third-line treatment for gastric cancer patients whose tumors express PD-L1. Merck said the status of that indication remains unchanged.
- For Merck, the focus now turns to KEYNOTE-062, which is testing Keytruda as a monotherapy or in combination for first-line treatment of gastric cancer, and to KEYNOTE-585, which looks at Keytruda's efficacy in the neoadjuvant/adjuvant setting.
Keytruda's failure in second-line gastric cancer is the second time the blockbuster checkpoint inhibitor has won an accelerated approval in a disease setting only to later fall short in later studies.
In July, Merck revealed that a study testing Keytruda in previously treated head and neck squamous cell carcinoma didn't extend overall survival, calling into question the drug's earlier approval in that setting. For gastric cancer, the FDA had conditionally approved Keytruda as a third-line treatment in September, while the current setback is in second-line, an earlier setting.
In both cases, however, Merck has said the earlier approvals would remain unchanged.
KEYNOTE-061 didn't show a significant lengthening of overall survival or of progression-free survival. This is particularly notable since the study only looked at patients whose tumors express PD-L1, a group that normally would be expected to perform better.
Merck's previous study in third-line showed treatment with Keytruda led to a response in 13.3% of patients with a PD-L1 combined positive score greater than or equal to one. Only 1.4% experienced a complete response, however, suggestive of a less durable effect.
Other checkpoint inhibitors have fallen short in gastric cancer as well. Late last month, Pfizer Inc. and Merck KGaA announced their PD-L1 inhibitor Bavencio didn't meet its primary endpoint of overall survival in patients with advanced gastric cancer that can't be removed surgically.
Gastric cancer is relatively common, and survival rates for advanced disease remain low. Keytruda remains the only checkpoint inhibitor approved for that cancer type, but Pfizer and other are conducting further studies.
While the setback likely won't impact Keytruda's steady commercial success, the clinical failures in gastric and head and neck cancer raise questions about the FDA's speed in approving checkpoint inhibitors on an accelerated basis with small data sets.