Merck & Co. already has an approval for Keytruda in tandem with Lenvima—a drug it shares with Eisai—in endometrial cancer. But the partners are trying to take the combo into additional cancers, and new data provide a glimpse of where it might go next.
Sunday at the European Society of Medical Oncology’s (ESMO's) virtual meeting, the pair trotted out phase 2 results showing the combo could provoke responses in patients across a range of tough-to-treat tumor types—though it fared better in some than in others.
In previously treated triple-negative breast cancer, for example, the duo spurred a response in 29% of patients, and 32.3% of ovarian cancer patients who had tried three other treatment options responded to the pairing, too. Meanwhile, 21.9% of non-microsatellite instability-high colorectal cancer patients recorded responses.
On the flip side, Keytruda and Lenvima didn’t do as well in third-line gastric cancer or second-line biliary tract cancer, recording a 9.7% response rate in each group. In second-line glioblastoma multiforme, a deadly brain cancer, 16.1% of patients responded.
Still, the results were strong enough to persuade Merck and Eisai to take a closer look. “The data was pretty promising in all of the tumor types that we’ve looked at, so we’ll be looking further at the combination in all of the tumor types that were studied,” Scot Ebbinghaus, Merck's vice president of clinical research, said.
Ebbinghaus called out ovarian cancer and colorectal cancer as two arenas that “looked particularly interesting” given that “they’ve been historically challenging to treat, and it’s been hard to show evidence that …anti-PD-1 drugs alone are active,” he said.
“Seeing real promising results in a combination, I think, kind of stuck out,” he added.
Those basket-trial data from the Leap-005 study followed close on the heels of other promising phase 2 results presented Saturday at ESMO.
In the Leap-004 study, Keytruda-Lenvima showed it could provoke responses in 21.4% of melanoma patients with advanced disease or tumors that couldn’t be surgically removed and whose cancer had advanced despite anti-PD-1/L1 therapy.
“I think it’s an important observation in a population that’s defined as being strictly refractory to anti-PD-1,” Ebbinghaus noted. “In diseases like melanoma where anti-PD-1 therapies have become the sort of first-line standard of care, it creates a high unmet need for what happens to the patients who fail to respond, or respond and then progress.”
Merck and Eisai are looking to rack up additional approvals for the Keytruda-Lenvima combo after winning a nod in endometrial cancer last year. The duo’s prospects looked good in liver cancer after May’s American Society for Clinical Oncology meeting, but shortly thereafter the FDA issued an approval to Roche’s Tecentriq in the same setting based on more mature clinical results—and then hit Merck and Eisai with a rejection.
Regulators decided the companies’ early data “do not provide evidence that Keytruda in combination with Lenvima represents a meaningful advantage over available therapies,” Merck and Eisai said at the time.