Merck said the pivotal Phase 3 TroFuse-005 trial of sacituzumab tirumotecan (sac-TMT), an investigational TROP2-directed antibody-drug conjugate being developed with Kelun-Biotech, met its primary endpoints of overall survival (OS) and progression-free survival (PFS) in certain patients with advanced or recurrent endometrial cancer. The study evaluated sac-TMT against treatment of physician’s choice (doxorubicin or paclitaxel) in patients whose disease had progressed after platinum-based chemotherapy and anti-PD-1/L1 immunotherapy given either together or sequentially.
At a pre-specified interim analysis, sac-TMT showed a statistically significant and clinically meaningful improvement in both OS and PFS versus chemotherapy in this setting. The trial also met its key secondary endpoint of objective response rate. Merck plans to present the data at an upcoming medical meeting and to discuss the results with regulatory authorities worldwide.
The safety profile of sac-TMT in TroFuse-005 was consistent with prior studies, and no new safety signals were observed. Domenica Lorusso, MD, the study’s global lead investigator and a professor of obstetrics and gynecology at Humanitas University and Humanitas San Pio X in Milan, said the findings indicate sac-TMT may address an unmet need for patients with advanced endometrial cancer, a disease that is increasing in both incidence and mortality. She noted that patients whose cancer progresses after platinum and immunotherapy “are urgently in need of new options,” and that these data are the first to show a TROP2 ADC may be effective in this setting.
Dean Y. Li, MD, PhD, president of Merck Research Laboratories, said the TroFuse program reflects the company’s commitment to advancing its antibody-drug conjugate pipeline and builds on its research in gynecologic cancers. He said the TroFuse-005 findings support the view that sac-TMT, which uses a proprietary bifunctional linker intended to maximize delivery of the cytotoxic payload to tumors while limiting effects on healthy cells, could become an important component of treatment for certain patients with advanced endometrial cancer.
TroFuse-005 is the first Phase 3 study from Merck’s TroFuse clinical development program for sac-TMT to report positive results. The program includes 17 ongoing global Phase 3 trials across multiple tumor types and disease stages, including 10 Phase 3 studies in women’s cancers. Sac-TMT is being evaluated as monotherapy and in combination with immunotherapies in endometrial, bladder, breast, cervical, gastric, non-small cell lung and ovarian cancers, including the ongoing TroFuse-033 trial in first-line mismatch repair–proficient endometrial cancer.
Subscribe to our e-Newsletters
Stay up to date with the latest news, articles, and events. Plus, get special offers
from American Pharmaceutical Review – all delivered right to your inbox!
Sign up now!