MSD's Sac-TMT delivers in first phase 3 readout

MSD's TROP2-targeting antibody-drug conjugate (ADC) sacituzumab tirumotecan (sac-TMT), licensed from China's Kelun-Biotech, has improved survival in a late-stage endometrial cancer trial.

The positive result in what is the first pivotal trial readout for sac-TMT, which is already approved for marketing as a lung and breast cancer therapy in China, is an endorsement of MSD's decision to license rights to the drug in 2022 in a deal valued at up to $1.4 billion.

The TroFuse-005 study makes sac-TMT the first anti-TROP2 ADC to improve progression-free survival (PFS) and overall survival (OS) in patients with advanced or recurrent endometrial cancer who have progressed after platinum-based chemotherapy and anti-PD-1/PD-L1 immunotherapy, according to MSD, which is known as Merck & Co in the US and Canada.

The data from the study will be reported at a later date, said MSD, but reveal a "statistically significant and clinically meaningful" improvement for sac-TMT compared to physician's choice of chemotherapy with doxorubicin or paclitaxel. The company said it plans to share the results with regulatory authorities around the world.

"These results show sac-TMT may be able to address a critical unmet need for certain patients with advanced endometrial cancer, one of the only cancers increasing in both incidence and mortality worldwide," said lead investigator Dr Domenica Lorusso of Humanitas University and Humanitas San Pio X in Milan, Italy.

"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 in this setting," she added.

Current drugs in the TROP2 ADC class are Gilead Sciences' Trodelvy (sacituzumab govitecan) – used to treat triple-negative and HR-positive, HER2-negative breast cancer – and AstraZeneca/Daiichi Sankyo's Datroway (datopotamab deruxtecan) for HR+/HER2- breast cancer and EGFR-mutated non-small cell lung cancer (NSCLC).

The TroFuse-005 readout, one of 17 international phase 3 trials in the TruFuse programme currently being carried out across multiple tumour types, could give MSD a first-to-market advantage for a TROP2 drug in endometrial cancer and allow it to build a commercial presence before going head-to-head with its rivals.

"The scale and ambition of our expansive TroFuse program reflects our deep commitment to advancing one of the industry’s leading ADC pipelines to make a difference for more people facing cancer,” said Dr Dean Li, president of Merck Research Laboratories.

"These findings reinforce our belief that sac-TMT, with its proprietary bifunctional linker designed with the intent to maximise payload delivery to tumours while minimising impact on healthy cells in the body, has the potential to become a cornerstone in the treatment of certain patients with advanced endometrial cancer," he added.