Merck & Co.’s Keytruda has a poor track record in stomach cancer, with two failed pivotal trials in newly diagnosed and previously treated patients. But the drug has redeemed its reputation in the field with a quick FDA nod for a subset of patients.
Keytruda, used in tandem with Roche’s anti-HER2 mainstay Herceptin and chemotherapy, has won FDA clearance to treat new patients with HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma, Merck said Wednesday.
SVB Leerink analyst Daina Graybosch, Ph.D., called the go-ahead a “positive surprise” because it’s based on interim tumor response data. The approval keeps Keytruda in the stomach cancer market, which has become increasingly important for makers of PD-1/L1 inhibitors, she said in a Wednesday note to clients.
About 10,000 newly diagnosed gastric/GEJ cancer patients are treated each year in the U.S., with about a quarter being HER2-positive. That represents a $300 million opportunity, Graybosch said.
The FDA based the decision on early data from the phase 3 Keynote-811 trial. In the first 264 patients randomized in the 692-subject trial, the Keytruda regimen significantly shrunk tumors in 74% of patients, a 22-percentage-point improvement over the Herceptin-chemo group.
The nod once again puts Keytruda in competition with Bristol Myers Squibb’s Opdivo, which a few days ago became the first immuno-oncology agent approved for previously untreated gastric cancer. That go-ahead is, however, based on life-extension data from the phase 3 CheckMate-649 trial, which paired Opdivo with chemo and excluded patients with HER2-positive tumors.
Although Opdivo’s and Keytruda’s approvals give them separate markets divided by HER2 status, Graybosch suggested patient selection will come down to physician preference.
“We believe physicians and payers would view Opdivo and Keytruda as interchangeable in setting,” Graybosch said in the note.
In the earlier Keynote-062 trial, Keytruda and chemotherapy failed to top solo chemo at extending the lives of front-line patients with PD-L1-positive, HER2-negative disease. Graybosch suggested that failure was likely caused by the trial’s statistical design.
Single-agent Keytruda also failed as a second-line treatment in the Keynote-061 study. Those two flops prompted an external FDA panel to vote 6-2 last week in favor of the agency removing an accelerated approval for the Merck drug in third-line gastric/GEJ cancer.
The advisers pointed to Opdivo’s freshly minted front-line nod to explain their decisions, suggesting checkpoint inhibitors would likely be used earlier. The new approval now catapults Keytruda into that market.
Because the new Keytruda front-line indication also came through the accelerated approval pathway, Merck will be required to confirm the regimen’s benefits with gold-standard patient survival data.
Merck is also running the phase 3 Keynote-859 trial, which tests the combination of Keytruda and chemotherapy for newly diagnosed patients with advanced gastric or GEJ adenocarcinoma.