Merck's TROP2 ADC Shows Promise in Lung and Breast Cancer Trials

Merck & Co.'s ambitious development program for its TROP2 antibody-drug conjugate (ADC) sacituzumab tirumotecan (sac-TMT) is gaining momentum, with the company's Chinese partner Kelun-Biotech reporting positive phase 3 results in lung and breast cancer at the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin.

Impressive Results in EGFR-Mutant Non-Small Cell Lung Cancer

In the OptiTROP-Lung04 trial, sac-TMT demonstrated significant efficacy in patients with tyrosine kinase inhibitor-pretreated EGFR-mutant non-small cell lung cancer (NSCLC). The drug reduced the risk of death by 40% compared to chemotherapy, with median overall survival (OS) not yet reached in the sac-TMT arm versus 17.4 months in the chemotherapy group.

Progression-free survival (PFS) was also improved, with sac-TMT showing a 51% risk reduction and a median PFS of 8.3 months compared to 4.3 months for chemotherapy. These benefits were observed across various subgroups, including patients with brain metastases and different EGFR mutation types.

Based on these results, Chinese authorities have already approved sac-TMT as a second-line treatment for EGFR-mutant NSCLC. Merck is now attempting to replicate this success globally through the TroFuse-009 and TroFuse-004 trials.

Strong Performance in HR-Positive, HER2-Negative Breast Cancer

The OptiTROP-Breast02 trial revealed equally impressive results for sac-TMT in previously treated HR-positive, HER2-negative breast cancer. The ADC reduced the risk of progression or death by 65% compared to chemotherapy, more than doubling the median PFS to 8.3 months versus 4.1 months for chemotherapy.

While overall survival data were not yet mature, preliminary results showed a 67% reduction in the risk of death favoring sac-TMT. These outcomes appear favorable when compared to AstraZeneca and Daiichi Sankyo's Datroway, which received FDA approval for this indication in January 2025.

Safety Profile and Future Directions

Both trials reported manageable safety profiles for sac-TMT, with similar rates of grade 3 or above treatment-related adverse events compared to chemotherapy. Stomatitis emerged as a notable side effect, occurring in 63-64% of sac-TMT patients, albeit mostly mild and manageable.

Marjorie Green, M.D., Merck's senior vice president and head of oncology global clinical development, expressed optimism about sac-TMT's potential, stating, "I anticipate, across multiple tumor types and multiple indications, this is a workhorse drug."

Merck is expanding its sac-TMT program rapidly, with 15 global phase 3 trials now underway. The company aims to build on Kelun's success in China and establish sac-TMT as a leading treatment option in multiple cancer types. As the landscape of TROP2 ADCs becomes increasingly competitive, with rivals like AstraZeneca and Gilead Sciences also advancing their candidates, the pharmaceutical industry eagerly awaits the results of ongoing global trials.