Merck Develops Novel Sacituzumab Tirumotecan for Advanced NSCLC Treatment
Merck has developed a groundbreaking treatment, sacituzumab tirumotecan (sac-TMT), for patients with advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) harbouring epidermal growth factor receptor (EGFR) mutations (exon 19 deletion [19del] or exon 21 L858R).
This therapy is intended for individuals whose disease has progressed following tyrosine kinase inhibitor (TKI) treatment and platinum-based chemotherapy.
Sac-TMT is an investigational antibody-drug conjugate (ADC) designed with three essential components: sacituzumab, a monoclonal antibody that specifically targets TROP2; a cytotoxic payload from the topoisomerase 1 inhibitor class; and a novel, irreversible yet hydrolysable linker that utilises proprietary conjugation technology to connect the antibody to the cytotoxic agent.
This design achieves an average drug-to-antibody ratio of 7.4, ensuring precise and effective delivery of the cytotoxic payload to target cells.
TROP2 is highly expressed in various epithelial-derived tumours and plays a role in tumour cell proliferation, invasion, and metastasis. TROP2-targeting ADCs, like sac-TMT, specifically bind to TROP2-expressing tumour cells to deliver cytotoxic effects. Clinical studies have demonstrated encouraging anti-tumour activity with this approach.
Sac-TMT recently secured its first marketing authorisation in China from the National Medical Products Administration (NMPA).
It is approved for treating adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have undergone at least two prior systemic therapies, including one for advanced or metastatic disease. This approval is based on findings from the Phase 3 OptiTROP-Breast01 study.
Globally, lung cancer remains the leading cause of cancer-related deaths, with approximately 2.4 million new cases and 1.8 million deaths reported in 2022. Non-small cell lung cancer accounts for 80 percent of all lung cancer cases. Among NSCLC patients, EGFR mutations are present in 14% to 38 percent of tumours worldwide.
