Merck's TROP2 ADC Shows Promise in Phase 3 Trials, Expanding Oncology Portfolio

Merck & Co. is making significant strides in the development of its TROP2 antibody-drug conjugate (ADC), sacituzumab tirumotecan (sac-TMT), with recent phase 3 trial results showcasing the drug's potential across multiple cancer types. The company's ambitious clinical program for sac-TMT, licensed from China's Kelun-Biotech, now includes 15 global phase 3 trials, marking a substantial investment in this promising therapeutic approach.

Positive Results in EGFR-Mutant NSCLC and HR+/HER2- Breast Cancer

At the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin, Kelun-Biotech presented encouraging data from two Chinese phase 3 trials of sac-TMT. In the OptiTROP-Lung04 trial, involving patients with tyrosine kinase inhibitor-pretreated EGFR-mutant non-small cell lung cancer (NSCLC), sac-TMT demonstrated a significant 40% reduction in the risk of death compared to chemotherapy. The median overall survival (OS) was not reached in the sac-TMT arm, while the chemotherapy group achieved 17.4 months.

Similarly, in the OptiTROP-Breast02 trial, sac-TMT showed impressive results in previously treated HR-positive, HER2-negative breast cancer patients. The drug reduced the risk of progression or death by 65% versus chemotherapy, with median progression-free survival (PFS) more than doubling to 8.3 months compared to 4.1 months for chemotherapy.

Safety Profile and Competitive Landscape

The safety profile of sac-TMT appears manageable, with similar rates of grade 3 or above treatment-related adverse events compared to chemotherapy in both trials. However, stomatitis emerged as a notable side effect, affecting 64% of patients in the lung cancer trial and 63% in the breast cancer study, albeit mostly mild and manageable.

Merck's sac-TMT is entering a competitive field, with AstraZeneca and Daiichi Sankyo's Datroway already approved for HR+/HER2- breast cancer. Cross-trial comparisons suggest potentially favorable performance for sac-TMT, though direct comparisons are not possible due to differences in trial populations.

Merck's Global Expansion Plans

Marjorie Green, M.D., Merck's senior vice president and head of oncology global clinical development, expressed optimism about sac-TMT's potential, describing it as a "workhorse drug" across multiple tumor types and indications. Merck is now focused on replicating the Chinese trial successes in global studies, including TroFuse-009 and TroFuse-004 for NSCLC, and TroFuse-010 for breast cancer.

As the company advances its ambitious clinical program for sac-TMT, the pharmaceutical industry watches closely to see if this TROP2 ADC will indeed become the versatile oncology tool that Merck envisions.