FDA Recognizes Sacituzumab Tirumotecan as Breakthrough Therapy for Specific NSCLC Patients

### **Merck’s Latest Lung Cancer Therapy Receives FDA Breakthrough Designation**
Merck, operating as MSD outside the USA and Canada, revealed that the U.S. Food and Drug Administration (FDA) has awarded a Breakthrough Therapy designation to sacituzumab tirumotecan (sac-TMT) aimed at patients with advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) possessing epidermal growth factor receptor (EGFR) mutations (specifically exon 19 deletion [19del] or exon 21 L858R). This covers individuals who have encountered disease progression after tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy treatments. Developed in collaboration with Kelun-Biotech, Sac-TMT is a promising TROP2-targeting antibody drug conjugate (ADC). The designation is influenced by findings from a phase 2 expansion segment within a phase 1/2 evaluation of sac-TMT in those with EGFR-mutated NSCLC, showcased at the 2023 American Society of Clinical Oncology Annual Meeting, along with additional data from two sections of a phase 2 study on patients treated with at least two previous therapies.
“This recognition by the FDA underscores the pressing need for innovative treatment solutions for people living with EGFR-mutated nonsquamous NSCLC,” remarked Dr. Scot Ebbinghaus, vice president of global clinical development at Merck Research Laboratories. “We are committed to advancing the development of ADCs, aiming to significantly enhance current treatment standards for certain cancer types.”
The Breakthrough Therapy designation from the FDA is intended to accelerate the development and review path for drugs designed for severe or life-threatening conditions. To receive this designation, preliminary clinical data must suggest potential substantial improvements over available treatments on key clinically meaningful measures. Advantages of this designation include increased guidance from FDA experts on crafting a streamlined development plan, a scientific liaison for faster assessment, and potential Priority Review eligibility if specific criteria are met.
Merck is aggressively pursuing the worldwide clinical development of sac-TMT, both as a standalone treatment and in combination with Keytruda (pembrolizumab), with 10 ongoing phase 3 trials targeting various solid tumors. Two active studies are TroFuse-004, comparing sac-TMT against standard chemotherapy (docetaxel or pemetrexed) for patients with prior treatment for EGFR-mutated or other genomic-altered NSCLC, and TroFuse-009, evaluating sac-TMT versus doublet chemotherapy (pemetrexed and carboplatin) for those previously treated with EGFR-mutated NSCLC. These are the sole phase 3 trials focusing on a TROP2 ADC in previously treated EGFR-mutated NSCLC.
In China, sac-TMT recently received its maiden marketing approval from the National Medical Products Administration (NMPA) for adult patients with inoperable locally advanced or metastatic triple-negative breast cancer (TNBC), conditioned on prior receipt of at least two systemic therapies (one at minimum for the advanced or metastatic stage), grounded on phase 3 OptiTROP-Breast01 study outcomes. Under a partnership, Kelun-Biotech retains the rights for sac-TMT’s development, manufacturing, and marketing within Greater China (comprising Mainland China, Hong Kong, Macau, and Taiwan).
Sac-TMT is composed of a TROP2-directed monoclonal antibody, sacituzumab, a cytotoxic agent from the topoisomerase 1 inhibitor class, and an innovative hydrolyzable linker connecting the antibody to the payload using proprietary conjugation technology. The average drug-to-antibody ratio is 7.4. TROP2 is noticeably present in various epithelial-derived tumors, encouraging tumor growth and spread. TROP2-directed ADCs specifically target TROP2-expressing tumors, delivering cytotoxic effects that have demonstrated promising anti-tumor activity in clinical research.
Kelun-Biotech, a subsidiary of Kelun Pharmaceutical, focused on R&D, production, commercialization, and global collaboration of cutting-edge biological and small molecule drugs, developed Sac-TMT. Under a partnership, Kelun-Biotech granted Merck exclusive rights to sac-TMT outside Greater China.
Lung cancer remains a leading cause of cancer-related deaths globally, with approximately 2.4 million new cases and 1.8 million deaths recorded in 2022 alone. Non-small cell lung cancer (NSCLC) represents 80% of these cases. EGFR mutations account for 14-38% of NSCLC tumors worldwide. The 2024 five-year survival rate for lung cancer patients in the U.S. is forecasted at 25%, reflecting advancements in early detection, surgical techniques, and new targeted therapies. Continued emphasis on early detection and screening is vital, as nearly 44% of cases are diagnosed only when advanced.