Promising Sac-TMT Receives FDA Breakthrough Therapy Designation for Lung Cancer

The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to sacituzumab tirumotecan (sac-TMT) for advanced NSCLC with EGFR mutations. This TROP2-targeting ADC has demonstrated promising results in Phase 1/2 trials. Already approved in China for breast cancer, sac-TMT offers hope for improved outcomes in hard-to-treat cancers.

This designation highlights the potential of sac-TMT as a treatment for advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) with EGFR mutations in patients whose disease has progressed following a tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy. Sac-TMT is an investigational antibody-drug conjugate (ADC) developed by Merck in collaboration with Kelun-Biotech.

“This designation by the FDA highlights the importance of developing novel therapeutic options for patients living with EGFR-mutated nonsquamous NSCLC. 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,” said Dr. Scot Ebbinghaus, Vice President, Global Clinical Development, Merck Research Laboratories.

A Promising Milestone in Lung Cancer Treatment

Sac-TMT targets TROP2, a protein frequently overexpressed in various epithelial-derived tumors. It combines three innovative components: a TROP2-targeting monoclonal antibody, a cytotoxic topoisomerase 1 inhibitor payload, and a novel linker technology designed for precision delivery of the drug. The FDA's decision is based on compelling data from a Phase 1/2 study and additional Phase 2 trials demonstrating the drug’s effectiveness in patients with EGFR-mutated NSCLC treated with at least two prior therapies.

Global Development and Research

Merck is pursuing an ambitious global clinical development program for sac-TMT, both as a standalone therapy and in combination with KEYTRUDA® (pembrolizumab). Currently, ten Phase 3 trials are evaluating the drug across various cancers, including two pivotal studies in EGFR-mutated NSCLC:

• TroFuse-004: Comparing sac-TMT with standard chemotherapy (docetaxel or pemetrexed).
• TroFuse-009: Assessing sac-TMT versus doublet chemotherapy (pemetrexed and carboplatin).

These trials mark a critical step as the only Phase 3 studies examining a TROP2-targeted ADC for previously treated EGFR-mutated NSCLC.

Beyond Lung Cancer 

Sac-TMT has already achieved a regulatory milestone in China, receiving approval for treating advanced triple-negative breast cancer (TNBC) based on Phase 3 trial results. Kelun-Biotech holds development and commercialization rights in Greater China, while Merck oversees sac-TMT's advancement in other global markets.

About Author: Tracy Mokwe

With over 3 years of experience as a medical laboratory scientist and writer, I am passionate about translating complex scientific information into clear and accessible content. My expertise lies in medical sciences, laboratory science and research, digital health, AI, and cybersecurity in healthcare.