Pfizer and Merck's Bavencio Fails in Phase 3 Maintenance Therapy Trial for Refractory Gastric Cancer

Compiled by Fan Dongdong

Immuno-oncology therapies have shown limited efficacy in the treatment of gastric cancer; recently, Pfizer and Merck KGaA’s Bavencio also failed to achieve success in trials for refractory gastric cancer.

The two companies recently announced that in the Phase 3 maintenance therapy study (JAVELIN Gastric 100), Bavencio failed to outperform the other two treatment regimens—continued chemotherapy or best supportive care to prolong survival—in patients with advanced or unresectable gastric cancer who had successfully completed one line of chemotherapy. The study found that Bavencio did not demonstrate a significant therapeutic advantage, even among PD-L1-positive patients, a subgroup in which PD-1/PD-L1 inhibitors have historically shown better efficacy.

Markus Möhler, the coordinating investigator of the trial, stated in a press release that advanced gastric cancer “is rarely immunogenic, and to date, no immune checkpoint inhibitors have demonstrated superiority over the current standard of care with chemotherapy.” Researchers are now conducting an in-depth analysis of the results to extract meaningful insights.

In fact, this is not the first time Bavencio has failed in gastric cancer research. In 2017, researchers acknowledged that the drug failed to significantly improve overall survival rates in patients with advanced gastric cancer compared to current best treatments. Furthermore, even market-leading PD-1 inhibitors such as Keytruda have failed to achieve major breakthroughs in the treatment of gastric cancer. In late 2017, Keytruda failed to halt tumor progression or demonstrate a significant survival advantage in patients with previously treated, PD-L1-positive advanced gastric cancer (KEYNOTE-061). In April 2019, the KEYNOTE-062 trial also failed; compared with chemotherapy alone, the combination of Keytruda and chemotherapy showed no significant differences in overall survival or progression-free survival, thus failing to meet its clinical endpoints.

However, in the KEYNOTE-059 study, Keytruda previously demonstrated certain clinical benefits as a third-line treatment regimen for PD-L1-positive gastric cancer patients, which led to its accelerated approval by the U.S. FDA in 2017. Another blockbuster oncology drug, Opdivo, successfully improved survival rates among Asian gastric cancer patients when used as a third-line therapy. In the ONO-4538-12 trial, the drug reduced the risk of death in gastric cancer patients by 37%, extending median overall survival by 5.32 months, compared with 4.14 months in the placebo group.

Although there appears to be no breakthrough in gastric cancer, Bavencio has already gained approval from the U.S. FDA for renal cell carcinoma. The FDA previously approved Bavencio in combination with Pfizer’s targeted anticancer drug Inlyta as a first-line treatment for patients with advanced renal cell carcinoma. However, the future prospects for this drug are not particularly optimistic, as this combination will face competition from the Keytruda + Inlyta and Opdivo + Yervoy regimens.

In addition to setbacks in gastric cancer, Bavencio has also faced three setbacks in ovarian cancer trials, the most recent of which involved its combination with Pfizer’s PARP inhibitor Talzenna for patients with previously untreated stage III or IV ovarian cancer.

Reference Source: Pfizer, Merck KGaA's Bavencio flunks study in hard-to-treat gastric cancer