Merck, Kelun score with sac-TMT in endometrial cancer trial

 Over the last 18 months, Merck and Kelun-Biotech have notched four approvals in China for their TROP2-directed antibody-drug conjugate (ADC) sacituzumab tirumotecan (sac-TMT).

And now, after meeting the primary endpoints in a phase 3 trial of certain patients with advanced or recurrent endometrial cancer, the companies are taking steps to gain clearance of sac-TMT in another indication. 

In a pre-specified interim analysis, sac-TMT provided statistically significant and clinically meaningful improvement in overall survival (OS) and progression-free survival (PFS) versus a physician’s choice of chemotherapies doxorubicin or paclitaxel. The study, which also achieved its key secondary endpoint of objective response rate (ORR), included 776 patients with endometrial carcinoma and carcinosarcoma who had previously received platinum-based chemo and anti-PD-1/L1 immunotherapy either together or sequentially.

It is the first global phase 3 trial to demonstrate statistically significant improvement in both OS and PFS compared to chemotherapy in this group of patients, the companies added. And it marks the first global phase 3 win from Merck’s extensive TroFouse clinical program for sac-TMT. 

The safety profile was consistent with prior sac-TMT studies, with no new signals identified. The data will be presented at an upcoming medical meeting and discussed with regulatory authorities around the world, the companies said.

“Despite recent advances, patients whose disease progresses following treatment with platinum and immunotherapy are urgently in need of new options, and these findings show for the first time that a TROP2 ADC may be an effective option,” Domenica Lorusso, M.D., of Humanitas University, the study’s lead investigator, said in a release.

Since forming their partnership in 2022, Merck and Kelun have built a massive clinical trial program, which includes 17 ongoing global phase 3 studies of sac-TMT. The companies will present readouts from lung and breast cancer trials at the American Society of Clinical Oncology annual meeting later this month in Chicago.

Merck has received a Commissioner’s National Priority Voucher (CNPV), which will significantly shorten the FDA’s review time of sac-TMT once the company submits for approval. 

Merck’s effort comes as it is gearing up for the loss of exclusivity (LOE) at the end of this decade for cancer powerhouse Keytruda, which accounted for nearly half of the company’s $16.3 billion in sales in the first quarter of this year.  

Merck is playing catch-up in the TROP2-directed ADC space. Gilead was first to the market with its blockbuster Trodelvy in 2020, followed last year by AstraZeneca and Daiichi Sankyo with Datroway. 

“Merck is positioning its next wave of oncology products and broader pipeline to offset the anticipated Keytruda LOE, which in our view remains a headwind that is slowly decreasing in impact with continued (business development) and positive clinical catalysts,” Citi analyst Geoffrey Meacham wrote in a note to clients. 

The first approval for sac-TMT in China came in November of 2024 for third-line triple-negative breast cancer, followed by two nods for non-small cell lung cancer and one for HER+/HER2 breast cancer. 

https://www.fiercepharma.com/pharma/merck-kelun-score-sac-tmt-endometrial-cancer-trial