The world’s best-selling medicine is still adding new uses, and its latest FDA approval marks a first in the cancer immunotherapy class.
Merck & Co.’s Keytruda has received the FDA’s green light for use in combination with chemotherapy, followed by the PD-1 inhibitor as a single agent, in patients with primary advanced or recurrent endometrial cancer, the company said Monday.
The approval marks the 40th U.S. indication for Keytruda, which generated $25 billion in sales globally last year.
The new nod also allows Keytruda to leapfrog GSK’s rival PD-1 inhibitor Jemperli, which in July 2023 got the FDA’s blessing in first-line endometrial cancer. But Keytruda’s approval still claims a first because it covers tumors regardless of their mismatch repair status, which is a genomic biomarker. Jemperli’s nod, at least for now, is limited to a small subset of patients whose cancer is mismatch repair deficient (dMMR).
Keytruda won over the FDA this time with data from the phase 3 NRG-GY018 trial, or Keynote-868. In the study, the Keytruda-chemo regimen cut the risk of disease progression or death by 70% in dMMR patients and by 40% in patients with mismatch repair proficient (pMMR), compared with chemo alone. The data are slightly different from when the results of the study were first published last year.
In the dMMR cohort, patients in the control arm lived a median of 6.5 months without disease progression, and the median was not reached for Keytruda. As to the pMMR group, the median progression-free survival was 8.5 months and 11.1 months for the two arms, respectively.
At the interim analysis, data on whether Keytruda could extend patients’ lives remained immature with 12% deaths in the dMMR cohort and 17% in the pMMR population, according to the drug’s updated label. Although the exact overall survival data remain unclear, the FDA approval likely indicates that there’s at least no sign of any potential harm to patients’ life expectancy.
While Keytruda is the first to reach a broad first-line endometrial cancer population, Jemperli’s expansion beyond the dMMR subgroup may not be far away.
After a longer follow-up of part 1 of the phase 3 RUBY trial, GSK’s application to expand Jemperli’s nod to include pMMR patients has been accepted by the FDA under priority review. The target decision date is August 23 this year.
In the RUBY trial, Jemperli and chemo significantly reduced the risk of death by 31% in endometrial cancer patients regardless of their tumor’s mismatch repair status. As such, Jemperli became the first PD-1/L1 inhibitor to claim a statistically significant overall survival win in first-line endometrial cancer in an overall population.
In the pMMR subgroup, the Jemperli-chemo combo showed a “clinically meaningful trend” in reducing the risk of death by 21% versus chemo alone, according to data released in March.
News of Keytruda’s latest approval came on the same day of an AstraZeneca announcement that its PD-L1 inhibitor Imfinzi has also secured an FDA approval in first-line dMMR endometrial cancer as part of a combination with chemo. An AZ spokesperson said the company will continue to evaluate overall survival data to potentially help Imfinzi reach even more patients.
Besides, both GSK and AZ are assessing adding a PARP inhibitor to their respective immunotherapies with positive findings so far. But neither company has made any regulatory progress with their PARP-containing cocktails.