Merck, building on Keytruda's landmark biomarker nod, pressures GSK's limited I-O position with new FDA approval

In a historic FDA go-ahead in 2017, Merck & Co.’s Keytruda became the first treatment for cancers with a specific genetic feature regardless of their location. Now, the immunotherapy has expanded its label in one cancer subtype with that biomarker, further pressuring a latecomer by GlaxoSmithKline.

Keytruda has won an FDA go-ahead for previously treated patients with advanced endometrial carcinoma that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), Merck said Monday.

Through a 2017 nod, Keytruda already covers all previously treated MSI-H/dMMR tumors, but it’s restricted to patients who have no alternative treatment options. But now, at least in endometrial cancer, the PD-1 inhibitor is allowed in any setting after prior systemic therapy, as long as the patients are not candidates for curative surgery or radiation. MSI-H/dMMR is most commonly found in endometrial and colorectal cancers.

Hormone therapy, Roche’s Avastin and Novartis’ mTOR inhibitor Afinitor are currently utilized—typically alongside chemotherapy—for treating endometrial cancer, even though they may not bear official FDA blessings. Endometrial cancer with an NTRK gene fusion abnormality is also eligible for treatment with Roche’s Rozlytrek or Bayer’s Vitrakvi thanks to their pan-tumor approvals. Now, with the new approval, Keytruda can target those patients with other treatment options as well.

The endometrial cancer indication, which was covered in the original pan-tumor accelerated approval, has now been converted into a full approval, a Merck spokesperson confirmed to Fierce Pharma. The New Jersey pharma is still under FDA requirement to collect additional datasets from other tumor types to confirm the broader tumor-agnostic nod, the spokesperson said.

Keytruda’s latest label adds new data from 90 endometrial cancer patients enrolled in the nonrandomized Keynote-158 trial. In the study, the medicine shrank tumors in 46% of patients, including eradicating any signs of cancer in 12% of patients.

Of the responding patients, 68% had responses lasting at least a year, and 44% had responses lasting two years or longer.

The tumor response showing marks a slight improvement from the 36% included in Keytruda’s MSI-H/dMMR label from 14 previously treated endometrial cancer patients, including in Keynote-158.

The Keytruda expansion is bad news for GSK’s rival PD-1 inhibitor Jemperli, which got its initial FDA go-ahead last April in previously treated dMMR endometrial cancer, followed by a Keytruda-matching tumor-agnostic nod in August. For the endometrial cancer part of its label, Jemperli has no restriction regarding alternative treatment options.

In its own trial, dubbed Garnet, Jemperli registered a 44.7% tumor response rate in 104 endometrial cancer patients.

Besides Keytruda monotherapy, the Merck PD-1 drug is also allowed to be paired with Eisai-partnered Lenvima for advanced endometrial carcinoma that’s not MSI-H or dMMR after prior therapy.

Editor's note: This story has been updated with additional information from Merck.