Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to sacituzumab tirumotecan (sac-TMT) for the treatment of patients with advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations (exon 19 deletion [19del] or exon 21 L858R) whose disease progressed on or after tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy. Sac-TMT is an investigational trophoblast cell-surface antigen 2 (TROP2)-directed antibody drug conjugate (ADC) being developed in collaboration with Kelun-Biotech. This designation is based on data from the Phase 2 expansion cohort of a Phase 1/2 study evaluating sac-TMT in patients with EGFR-mutated NSCLC, which were presented at the 2023 American Society of Clinical Oncology Annual Meeting, as well as data from two parts of a Phase 2 study evaluating sac-TMT in patients with EGFR-mutated NSCLC who have been treated with at least two lines of prior therapy.

“This designation by the FDA highlights the importance of developing novel therapeutic options for patients living with EGFR-mutated nonsquamous non-small cell lung cancer,” said Dr. Scot Ebbinghaus, vice president, global clinical development, Merck Research Laboratories. “We believe ADCs are an important modality in the treatment of cancer and are rapidly advancing the clinical development of sacituzumab tirumotecan, with the goal of meaningfully improving upon current standards of care in certain cancers.”

The FDA’s Breakthrough Therapy designation is granted to expedite the development and review of medicines that are intended to treat serious or life-threatening conditions. To qualify for this designation, preliminary clinical evidence must indicate that the product may demonstrate substantial improvement over currently available options on at least one clinically significant endpoint. The benefits of this Breakthrough Therapy Designation include more intensive guidance from the FDA on an efficient development program, access to a scientific liaison to help accelerate review time and potential eligibility for Priority Review if relevant criteria are met.

Merck is rapidly advancing the global clinical development program evaluating sac-TMT as a monotherapy and in combination with KEYTRUDA ^® (pembrolizumab) with 10 ongoing Phase 3 studies across various solid tumors. Two of these ongoing trials include TroFuse-004, which is evaluating sac-TMT versus chemotherapy (docetaxel or pemetrexed) in patients with previously treated NSCLC with EGFR mutations or other genomic alterations, and TroFuse-009 which is evaluating sac-TMT versus doublet chemotherapy (pemetrexed and carboplatin) in certain patients with previously treated EGFR-mutated NSCLC. These are the only Phase 3 trials evaluating a TROP2 ADC in previously treated EGFR-mutated NSCLC.

Sac-TMT recently received its first marketing authorization 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) who have received at least two prior systemic therapies (at least one of which is for advanced or metastatic stage), based on results from the Phase 3 OptiTROP-Breast01 study. Under a collaboration agreement, Kelun-Biotech maintains the rights to develop, manufacture and commercialize sac-TMT in Greater China (which includes Mainland China, Hong Kong, Macau and Taiwan).