Merck & Co.’s Keytruda has hit its marks in many tumor types but doesn’t exactly have a successful clinical history in stomach cancer. Now, the drug can at least tout an early win for a subgroup of patients.
Combining Keytruda with Roche’s Herceptin and chemotherapy shrank tumors in 74.4% of patients with newly diagnosed, HER2-positive gastric or gastroesophageal junction cancer, Merck said at the virtual American Society of Clinical Oncology meeting. That’s significantly more than the 51.9% for the standard-of-care Herceptin-chemo regimen.
The FDA obviously liked what it saw, having already granted Keytruda a quick go-ahead based on this interim data from the first 264 patients enrolled in the planned 692-subject trial—even before the official data presentation.
The agency actually encouraged Merck to file for approval with the tumor response data from this ongoing trial, which is examining Keytruda’s ability to stall tumor progression and extend patients’ lives, Scot Ebbinghaus, M.D., Merck’s vice president of clinical research, said in an interview.
Ebbinghaus said the phase 3 Keynote-811 data show a “very remarkable treatment effect.” At the median follow-up of 12 months, the median duration of response was 10.6 months for the Keytruda cocktail, versus 9.5 months for the Herceptin-chemo arm. Keytruda also eradicated signs of cancer in 11.3% of patients, compared with 3.1% for the control group.
Tumor response data also won Keytruda its accelerated FDA nod in third-line stomach cancer nod in 2017. But after two failed confirmatory trials in the second- and front-line settings, that conditional approval’s now in danger; an FDA advisory panel recently recommended the agency strip Keytruda of that indication. In its own analysis, the agency pointed out that it doesn’t believe single-agent Keytruda has a future in stomach cancer treatment.
Despite the prior Keytruda-chemo combo flop in newly diagnosed patients, Ebbinghaus argued the new indication in HER2-positive patients shouldn’t be affected.
“There’s generally a fairly wide acknowledgement in the expert community that anti-PD-1 agents are active in gastric cancer in certain settings,” he said. “I think there’s a high degree of confidence that … specifically [Keytruda] is an active agent that adds meaningfully to the treatment of, in this case, patients with HER2-positive gastric cancer.”
Learning from its Keynote-061 and Keynote-062 flops and determined to prove Keytruda’s worth in the broader HER2-negative gastric cancer market, Merck has adjusted its phase 3 Keynote-859 trial for that indication. It’s now aiming to enroll more than 1,500 patients for the expanded trial and has redesigned the statistical markers.
Now, Merck has a “fairly high degree of confidence” that the new study will be successful, Ebbinghaus said. HER2-positive disease makes up about a quarter of all gastric cancer cases in the U.S., he said.
Meanwhile, a Keytruda rival, Bristol Myers Squibb’s Opdivo, has snagged a front-line stomach cancer nod with life extension data from a trial in HER2-negative patients. In a recent note to investors, SVB Leerink analyst Daina Graybosch, Ph.D., suggested physicians will use both drugs regardless of patients’ HER2 status.
“We believe physicians and payers would view Opdivo and Keytruda as interchangeable in [that] setting,” she wrote in the note.