Keytruda PhIII failure in gastric cancer blights Merck's quest for frontline dominance
A year and a half after scoring an approval to use Keytruda in third-line gastric cancer, Merck has run into a wall trying to apply the PD-1 star in the frontline setting.
In an update for the KEYNOTE-062, the company $MRK disclosed that Keytruda as a monotherapy proved non-inferior to chemotherapy — the current standard of care for advanced gastric or gastroesophageal junction adenocarcinoma — in overall survival. In combination, though, Keytruda plus chemo was not found to be superior for either OS or progression-free survival compared with chemo alone. That likely meant more misses than hits in the primary endpoints, listed as PFS and OS on clinicaltrials.gov.
As a spokesperson explained:
Based on the pre-specified statistical analysis plan, superiority testing for OS in the KEYTRUDA monotherapy group was conducted, however as announced, the final analysis showed that KEYTRUDA monotherapy was non-inferior, not superior, to the chemotherapy arm in patients whose tumors were CPS ≥1. For KEYNOTE-062, it made sense to test for noninferiority in the event that KEYTRUDA monotherapy had comparable efficacy as chemotherapy with a potentially favorable safety and tolerability profile.
Merck went ahead with the Phase III trial despite a flop in the second-line setting of the same indication in 2017. Granted, the drug had positive third-line data going for it in a tough disease where Pfizer and Merck KGaA’s PD-L1 drug Bavencio failed.
All patients in the trial had tumors that express PD-L1. Investigators did not tease out any differences between those with a high combined positive score (CPS ≥10) and those with low CPS, of 1 or above.
“Gastric cancer is historically difficult to treat, and unfortunately continues to be associated with high mortality rates in many countries, particularly in the metastatic stage,” said Roy Baynes, Merck’s head of global development, in a statement.
The brief statement also didn’t cover any of the secondary endpoints, including overall response rate, duration of response, quality of life and a gastric cancer score.
Merck says it plans to discuss the final analysis with the FDA, as well as other ongoing gastric studies that might serve as confirmatory trials, including KEYNOTE-811 and KEYNOTE-859. Then there’s the Phase III KEYNOTE-585 to watch, where Keytruda in combination with chemotherapy is tested in a neoadjuvant/adjuvant setting.