Merck known as MSD outside the U.S. 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 advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Specifically, this includes patients with exon 19 deletions or exon 21 L858R mutations whose disease has progressed after treatment with tyrosine kinase inhibitors (TKIs) and platinum-based chemotherapy.
Sac-TMT is an investigational antibody-drug conjugate (ADC) that targets trophoblast cell-surface antigen 2 (TROP2), a protein expressed in several types of cancer. It is being developed in partnership with Kelun-Biotech. The FDA granted this designation based on positive results from a Phase 2 expansion cohort of an ongoing Phase 1/2 study, as well as data from two parts of a Phase 2 study that evaluated sac-TMT in patients with EGFR-mutated NSCLC who had received at least two prior lines of therapy.
“This designation underscores the urgent need for novel treatments for patients with EGFR-mutated nonsquamous NSCLC,” said Dr. Scot Ebbinghaus, Vice President of Global Clinical Development at Merck Research Laboratories. “We believe that ADCs represent a promising approach in cancer treatment and are excited to advance sacituzumab tirumotecan, aiming to provide a meaningful improvement over current treatment options in certain cancers.”
The FDA’s Breakthrough Therapy designation is awarded to investigational treatments for serious or life-threatening conditions, where preliminary clinical evidence suggests the medicine may offer substantial improvements over available options. This designation facilitates more intensive guidance from the FDA, speeding up the development process and review times. It also potentially qualifies the treatment for Priority Review if the criteria are met, ensuring quicker access to new therapies for patients in need.
Merck has been advancing sac-TMT’s global clinical development in multiple solid tumors, both as a monotherapy and in combination with other treatments, including the immune checkpoint inhibitor KEYTRUDA® (pembrolizumab). There are currently 10 ongoing Phase 3 trials, including two that focus on NSCLC with EGFR mutations. TroFuse-004 is investigating sac-TMT compared to chemotherapy options (docetaxel or pemetrexed) in patients with previously treated EGFR-mutated NSCLC or other genomic alterations. TroFuse-009 is evaluating sac-TMT versus doublet chemotherapy (pemetrexed and carboplatin) in certain EGFR-mutated NSCLC patients. These trials represent the only Phase 3 studies evaluating a TROP2-targeted ADC in previously treated EGFR-mutated NSCLC.
In addition to its ongoing studies in NSCLC, sac-TMT recently received its first marketing approval in China from the National Medical Products Administration (NMPA). It was authorized for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have previously received at least two systemic therapies. This approval was based on the Phase 3 OptiTROP-Breast01 study results. Under a collaboration agreement, Kelun-Biotech holds the rights to develop, manufacture, and commercialize sac-TMT in Greater China, which includes Mainland China, Hong Kong, Macau, and Taiwan.
Merck’s progress with sac-TMT reflects its commitment to developing targeted therapies that address the unmet needs of patients with difficult-to-treat cancers. With the Breakthrough Therapy designation from the FDA, the company is poised to expedite the development and approval of this promising treatment. Sac-TMT’s potential to improve outcomes for patients with EGFR-mutated NSCLC and its broad clinical development program offer hope for many who currently have limited treatment options. The collaboration with Kelun-Biotech further strengthens Merck’s position in the global oncology landscape, particularly in the Asian market, where the demand for effective cancer therapies continues to grow.
As Merck advances sac-TMT through clinical trials and regulatory processes, the company remains focused on its goal of providing innovative therapies that can improve the lives of cancer patients worldwide. The development of sac-TMT, with its promising clinical profile and broad potential indications, may play a key role in the treatment of EGFR-mutated NSCLC and other cancers, marking a significant milestone in the fight against cancer.
