While Merck & Co.’s Keytruda already boasts a pair of approvals to treat certain forms of endometrial cancer, a recent effort to prove the PD-1 inhibitor’s worth as a post-surgery add-on therapy in newly diagnosed patients has fallen short.
Adjuvant treatment with Keytruda and chemotherapy—with or without radiotherapy—failed to hit the mark for disease-free survival (DFS) in newly diagnosed, high-risk endometrial cancer patients who received surgery with curative intent, according to an interim analysis of Merck’s late-stage KEYNOTE-B21 study. DFS refers to the length of time after a primary treatment ends that a patient survives without any signs or symptoms of their cancer.
The trial’s other primary endpoint, overall survival, was not formally tested because the Keytruda-chemo combo failed to reach statistical significance on the DFS metric, Merck said in a Thursday release.
Merck says it’s continuing a full evaluation of the data and is working with investigators to share the results at a later date.
Endometrial cancer is the sixth most common cancer in women and the most common type of cancer in the uterus, according to Merck. In the U.S. alone, the company estimates roughly 67,880 patients will be diagnosed with uterine body cancer this year. Merck also estimates there will be 13,250 patient deaths from the disease in 2024.
“While these results were not what we had hoped, we are focused on continuing to build on the established role of Keytruda in advanced endometrial carcinoma through our approved indications,” Gursel Aktan, M.D., Ph.D., vice president of global clinical development at Merck Research Laboratories, said in a statement.
Merck will continue to test Keytruda-based combinations—plus other treatment approaches like antibody-drug conjugates (ADC)—in endometrial and other types of gynecologic cancers, Aktan said.
Keytruda is already approved in patients with endometrial carcinoma that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). The PD-1 inhibitor picked up that nod in 2022 following a 2017 approval that allowed the drug to cover previously treated MSI-H/dMMR tumors in patients without alternative treatment options.
Keytruda also boasts a second indication alongside Eisai-partnered Lenvima in previously treated endometrial cancer that’s not dMMR.
Over the past year, Merck’s Keytruda has been sparring with GSK’s PD-1 rival Jemperli over endometrial cancer dominance in the clinic.
Last February, just two months after Jemperli snagged a historic win for immunotherapy in first-line endometrial cancer, Keytruda plus standard chemotherapy beat chemotherapy alone at staving off tumor progression or death in advanced or recurrent disease.
The following month at the Society of Gynecologic Oncology 2023 annual meeting, both GSK and Merck provided a closer look at their meds’ late-stage performance in first-line endometrial cancer, with Keytruda appearing to edge out Jemperli in MMR proficient (pMMR) patients—a key subgroup that Merck says comprises roughly two-thirds of all endometrial cancer cases.
GSK ultimately beat Merck to the finish line for a PD-1 nod in newly diagnosed disease, with the company’s Jemperli in July snagging FDA clearance as an add-on to chemotherapy for patients with primary advanced or recurrent endometrial cancer but only for tumors that are mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H).
Meanwhile, Merck and Eisai’s Keytruda-Lenvima combo in December missed the mark in a phase 3 study as a potential first-line treatment in certain patients with advanced or recurrent endometrial carcinoma. The oncology cocktail failed to demonstrate an improvement in overall survival and progression-free survival over a regimen of platinum-based chemotherapy, missing both of its primary endpoints.
While Keytruda climbed to the top of pharma's sales charts in 2023, the drug has experienced a series of clinical ups and downs in 2024.
The PD-1 inhibitor started out the year by delivering a partial win in a phase 3 study pitting the drug against high-risk localized muscle-invasive bladder cancer and locally advanced bladder cancer. Around the same time, Keytruda bolstered its case as a postsurgical treatment for resectable kidney cancer with data showing it helped slash the risk of death by 38% versus placebo post-kidney removal in patients with clear cell renal carcinoma—the most common form of kidney cancer.
The drug also posted a win in cervical cancer in March. But that same month, Keytruda in combination with Lynparza failed to improve patients’ life expectancy or delay progression or death when subbed in for the chemotherapy pemetrexed during maintenance treatment of newly diagnosed metastatic nonsquamous non-small cell lunger cancer.