Merck Secures Breakthrough Therapy Designation for Sacituzumab Tirumotecan (sac-TMT) in Advanced EGFR-Mutated Non-Small Cell Lung Cancer
Merck has announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to sacituzumab tirumotecan (sac-TMT). This investigational therapy is aimed at treating patients with advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) with specific epidermal growth factor receptor (EGFR) mutations (exon 19 deletion or exon 21 L858R). These patients must have experienced disease progression following treatment with tyrosine kinase inhibitors (TKIs) and platinum-based chemotherapy.
Sac-TMT is a TROP2-directed antibody-drug conjugate (ADC) developed in collaboration with Kelun-Biotech. The FDA's decision is based on data from a Phase 2 expansion cohort of a Phase 1/2 study as well as findings from two parts of a Phase 2 study involving patients with EGFR-mutated NSCLC who had undergone at least two prior therapies.
The Breakthrough Therapy designation aims to accelerate the development and review process for treatments addressing serious or life-threatening conditions. To qualify, preliminary clinical evidence must suggest significant improvement over current options on one or more clinically meaningful endpoints. The designation provides enhanced guidance from the FDA, a streamlined development program, and potential eligibility for Priority Review.
sac-TMT, both as a standalone therapy and in combination with KEYTRUDA® (pembrolizumab). The programme includes 10 ongoing Phase 3 trials across various solid tumours. Among these, the TroFuse-004 trial is evaluating sac-TMT against chemotherapy (docetaxel or pemetrexed) for previously treated NSCLC with EGFR mutations or other genomic alterations. The TroFuse-009 trial is comparing sac-TMT with a chemotherapy combination (pemetrexed and carboplatin) in certain patients with previously treated EGFR-mutated NSCLC. These trials are currently the only Phase 3 studies focusing on TROP2 ADCs for previously treated EGFR-mutated NSCLC.
In addition to its lung cancer studies, sac-TMT has received marketing authorisation in China from the National Medical Products Administration (NMPA) for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC). Approval was granted based on data from the Phase 3 OptiTROP-Breast01 study.
Sac-TMT is composed of three key components: a TROP2-targeting monoclonal antibody (sacituzumab), a cytotoxic payload derived from the topoisomerase 1 inhibitor class, and a novel linker that irreversibly but hydrolyzably binds the antibody to the payload using proprietary technology. The drug-to-antibody ratio averages 7.4. TROP2 is highly expressed in various epithelial-derived tumours, promoting tumour cell growth, invasion, and spread. TROP2 ADCs deliver cytotoxic effects directly to TROP2-expressing tumour cells, demonstrating promising anti-tumour activity in clinical trials.
Sac-TMT was originally developed by Kelun-Biotech, a subsidiary of Kelun Pharmaceutical. While Kelun-Biotech holds rights for the Greater China region, Merck has exclusive rights to develop, manufacture, and commercialise the therapy in all other territories.
