Merck’s Keytruda Flops in Late-Stage Endometrial Carcinoma Study

Merck Research Laboratories_iStock, Michael Vi

Pictured: Merck Research Laboratories in California/iStock, Michael Vi

Merck on Friday announced that the Phase III LEAP-001 trial of Keytruda (pembrolizumab) combined with Eisai’s Lenvima (lenvatinib) did not significantly improve survival in patients with advanced or recurrent endometrial carcinoma.

Without providing specific data, Merck said that patients who were given the Keytruda-Lenvima combo as a first-line therapy did not see significant improvements in overall survival (OS) or progression-free survival (PFS), compared with the standard of care, platinum-based doublet chemotherapy consisting of carboplatin and paclitaxel.

Gregory Lubiniecki, vice president of global clinical development at Merck Research Laboratories, said in a statement that the company was “disappointed” with LEAP-001’s results, particularly as Merck and Eisai were positioning the Keytruda-Lenvima combo as “another potential treatment option to patients when first diagnosed with certain types of advanced or recurrent endometrial carcinoma.”

Nonetheless, the partners remain “confident” in Keytruda and Lenvima and will continue to assess their combination in other difficult-to-treat cancers, according to Lubiniecki. The combo regimen remains approved for use in certain types of advanced endometrial carcinoma that had progressed after prior systemic therapy.

Despite failing to demonstrate significant efficacy, LEAP-001 found a favorable safety and tolerability profile for the combination regimen, with adverse events consistent with what had been established in prior trials.

LEAP-001 is a randomized and open-label study enrolling 842 patients with mismatch repair proficient or mismatch repair deficient advanced or recurrent endometrial carcinoma. The study’s results will not affect the other studies under Merck and Eisai’s LEAP clinical development program, which is assessing the combination of Keytruda and Lenvima in several different tumor types.

Friday’s failure comes one day after Merck posted back-to-back defeats for Keytruda in non-small cell lung cancer (NSCLC). On Thursday, the company announced that it failed a Phase II trial of the PD-1 blocker. When given with Merck's experimental anti-TIGIT antibody vibostolimab, Keytruda, with or without docetaxel, failed to significantly improved PFS in patients versus docetaxel alone.

The same day, Merck announced that it was also discontinuing the Phase III KEYLYNK-008 study after Keytruda, combined with AstraZeneca’s Lynparza (olaparib), did not elicit a significant improvement in OS.

The Keytruda-Lenvima combo has been on a losing streak. In April 2023, the treatment regimen fell short of its survival targets in unresectable or metastatic melanoma and in unresectable and metastatic colorectal cancer. In August 2023, Merck and Eisai posted another Phase III flop in head and neck cancer, forcing the partners to discontinue the study. In September 2023, Keytruda and Lenvima again sustained dual defeats in NSCLC.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

[11/1 7:34 PM] Tristan Manalac

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