Merck & Co.’s almighty Keytruda has become the first PD-1 inhibitor to show a benefit as a single agent for the front-line treatment of a subtype of endometrial cancer.
Keytruda significantly improved progression-free survival over platinum-based chemotherapy in patients with mismatch repair deficient (dMMR) advanced or recurrent endometrial cancer. The patients had either received no systemic chemotherapy or experienced recurrence more than six months after completing prior adjuvant therapy.
On its other dual primary endpoint, the Keynote-C93 trial also recorded an immature trend toward improvement in overall survival at the interim analysis. The trial is ongoing, with plans to evaluate the endpoint in the future.
The positive readout sets Keytruda up to be a new chemo-free option in first-line dMMR endometrial cancer, Brian Slomovitz, M.D., from Mount Sinai Medical Center and the study’s principal investigator, noted in a July 15 release. Merck now plans to share the results with regulatory authorities.
PD-1 inhibitors like Keytruda have been approved as single agents for previously treated dMMR endometrial cancer or in combinations with chemotherapy in first-line endometrial cancer.
In endometrial cancer, Keytruda’s main competitor is GSK’s Jemperli, which, despite being a latecomer in the overall cancer immunotherapy market, was the first PD-1 inhibitor to win an FDA approval in first-line endometrial cancer with a 2023 go-ahead for use alongside chemo in dMMR tumors. About two years ago, the FDA approved both PD-1 drugs in quick succession as combinations with carboplatin and paclitaxel for patients with primary advanced or recurrent endometrial cancer.
In their first-line endometrial cancer rivalry, GSK’s Jemperli benefits from a statistically significant overall survival improvement achieved in the phase 3 Ruby trial. By comparison, Keytruda’s Keynote-868 trial can’t yet claim a life extension benefit.
During GSK’s first-quarter earnings call in April, Nina Mojas, who leads the British drugmaker’s commercial operations as president of global product strategy, cited the significant OS benefit in endometrial cancer as the main driver of Jemperli’s 40% year-over year sales growth to 232 million pounds sterling ($313 million).
Keytruda previously suffered a setback in endometrial cancer when the phase 3 Keynote-B21 study testing the PD-1 drug in combination with chemotherapy as adjuvant treatment failed to meet its primary endpoint in newly diagnosed, high-risk tumors after surgery. That study remains ongoing to analyze results in the dMMR subgroup.
Both Merck and GSK are developing next-generation therapies for endometrial cancer.
In May, Merck reported the first global phase 3 win for its TROP2-directed antibody-drug conjugate, sac-TMT, partnered with China’s Kelun-Biotech. The TroFuse-005 trial met its primary endpoints of PFS and OS, as sac-TMT beat chemotherapy in patients with endometrial cancer who have previously received platinum-based chemo and immunotherapy.
A separate phase 3 trial coded TroFuse-033 is evaluating sac-TMT in the first-line maintenance setting among endometrial cancer that’s mismatch repair proficient.
As for GSK, the company recently advanced its B7-H4 ADC, mo-rez, into phase 3 testing in advanced endometrial cancer after recording a 67% overall response rate in a phase 1 trial. The drug is licensed from China’s Hansoh Pharma.