Pressure's on, GSK. Merck's Keytruda drops endometrial cancer win in first-line treatment

That didn’t take long. Just two months after GSK’s Jemperli touted immunotherapy’s first win in first-line endometrial cancer, Merck’s almighty Keytruda has followed with its own trial success.

Keytruda, used in tandem with standard chemotherapy, beat chemotherapy alone at staving off tumor progression or death in advanced or recurrent endometrial carcinoma, Merck said Friday. The improvement was statistically significant and clinically meaningful, the company added.

The positive readout came from the phase 3 NRG-GY018 trial, sponsored by the National Cancer Institute. Merck said it will discuss the results with regulatory authorities. The data could potentially support an FDA filing and move Keytruda up the endometrial cancer treatment sequence into the so-called first-line setting.

Keytruda’s win came two months after GSK said its PD-1 rival Jemperli, plus chemo, became the first cancer immunotherapy to deliver a progression-free survival win in a phase 3 first-line endometrial cancer study.

Both Jemperli and Keytruda are currently allowed as single agents in a subtype of endometrial cancer with the mismatch repair deficient (dMMR) biomarker. Keytruda also boasts an additional indication for use alongside Eisai-partnered Lenvima in previously treated endometrial cancer that’s not dMMR. And both NRG-GY018 and Jermperli’s RUBY trial have now reported benefits in slowing disease progression in all patients regardless of mismatch repair status at their interim analysis.

Endometrial cancer is the most common type of gynecologic cancer in the U.S., Ramez Eskander M.D., from the University of California, San Diego, and principal investigator of NRG-GY018, said in Friday's release. Those patients with recurrent disease following prior platinum-based adjuvant therapy or who are not amenable for surgery or radiation face a particularly poor prognosis and have limited treatment options, he said.

First-line endometrial cancer may be icing on the cake for Keytruda; after all, even without it, the Merck PD-1 inhibitor already surpassed $20 billion in sales in 2022. But for GSK, as chief commercial officer Luke Miels noted during an interview on the sidelines of the J.P. Morgan Healthcare Conference in January, the indication is expected to offer an inflection point for its PD-1 latecomer Jemperli.

With uptake now mainly in previously treated dMMR endometrial cancer, Jemperli only sold £21 million ($25 million) in 2022.

Data from the NRG-GY018 and RUBY trials will likely be carefully studied by industry watchers. That’s because GSK recently reported positive data for a Jemperli-Keytruda head-to-head phase 2 trial in newly diagnosed metastatic non-small cell lung cancer. In the study, Jemperli appeared better than Keytruda in their ability to shrink tumor and prevent disease worsening, even though the trial wasn’t designed to show superiority. Now, the endometrial trial will give industry watchers another opportunity to compare the two PD-1 inhibitors side by side.

Still, as Miels said during the JPM interview, GSK doesn’t intend to replace Keytruda, which has long established itself as the standard treatment in multiple tumor types. But by showing similar data as Keytruda, GSK wanted to “validate in physicians’ minds and the FDA’s mind” that Jemperli is comparable to the market leader, Miels said. And this could lay the foundation for Jemperli in its future combination plans with novel agents.