- Pfizer Inc. and Merck KGaA's checkpoint inhibitor Bavencio fell short of its objective in a Phase 3 trial testing the drug as a third line treatment for patients with metastatic gastric cancer that can't be removed through surgery.
- In the study, Bavencio failed to significantly extend overall survival compared to physicians' choice of two chemotherapies. No detailed data were disclosed, although Merck plans to present further details at a upcoming medical congress.
- The failure won't affect the companies' ongoing study of Bavencio as a first-line maintenance treatment following induction chemotherapy in patients with locally advanced or metastatic gastric cancer. Still, any setback stings for Pfizer and Merck, which are well behind the immuno-oncology leaders.
Pfizer and Merck KGaA — not to be confused with the U.S. pharma Merck & Co. — currently hold two accelerated approvals for Bavencio (avelumab) in the U.S., having secured a regulatory OK for metastatic Merkel cell carcinoma and second-line metastatic bladder cancer.
While several checkpoint inhibitors are approved in larger indications like melanoma, lung and bladder, only Merck & Co.'s Keytruda (pembrolizumab) holds an approval in gastric cancer.
Success in the JAVELIN Gastric 300 study would have given Pfizer and German Merck a potential path to challenge U.S. Merck in the third-line setting. Now, however, the two companies will likely have to wait until early 2019, when a study in first-line maintenance treatment of gastric cancer is expected to read out.
"We remain committed to our ongoing gastric cancer program with avelumab including the JAVELIN Gastric 100 study in the first-line switch maintenance setting," said Luciano Rossetti, head of R&D in Merck KGaA's biopharma business, in a Nov. 28 statement.
Gastric cancer (including gastroesophageal junction adenocarcinoma) is the fifth-most common cancer, according to Merck KGaA. But survival rates for advanced disease remain low and patients whose cancers progress after two lines of prior therapy have few other options.
In a study of Merck & Co.'s Keytruda, 13.3% of the 143 patients whose tumors expressed PD-L1 with a combined positive score greater or equal to one experienced a response — enough of a benefit for the Food and Drug Administration to grant an accelerated approval only for PD-L1-expressing gastric cancer patients.
Higher levels of PD-L1 generally seem to be correlated with better responses in studies of checkpoint inhibitors conducted to date. Focusing on this population first has served Merck & Co. well, allowing the company to catch early leader Bristol-Myers Squibb & Co.
Pfizer and Merck tested Bavencio in patients regardless of PD-L1 expression.
In addition to the other study in gastric cancer, the two companies have a trial in second-line non-small cell lung cancer and another in platinum resistant refractory ovarian cancer that should complete in 2018. Four others are expected to read out in 2019.