FDA Designates Sacituzumab Tirumotecan as Breakthrough Therapy for Specific Advanced NSCLC Patients

Merck, also known as MSD outside 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 advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) with specific epidermal growth factor receptor (EGFR) mutations. This decision is based on data from a Phase 1/2 study and a Phase 2 study, both of which assessed sac-TMT in patients with EGFR-mutated NSCLC who had undergone at least two previous lines of therapy. Sac-TMT is an investigational antibody drug conjugate (ADC) targeting the TROP2 protein, developed in collaboration with Kelun-Biotech.

Dr. Scot Ebbinghaus, Vice President of Global Clinical Development at Merck Research Laboratories, emphasized the significance of developing innovative treatment options for patients with this form of lung cancer. He highlighted that ADCs are an important modality in cancer treatment, and the company is committed to advancing the clinical development of sac-TMT to improve existing cancer treatment standards.

The FDA’s Breakthrough Therapy designation aims to speed up the development and review process for drugs intended to treat serious or life-threatening conditions. This designation is granted based on preliminary clinical evidence showing substantial improvement over existing treatments on at least one significant clinical endpoint. Benefits include more intensive guidance from the FDA, a scientific liaison to expedite review time, and potential eligibility for Priority Review.

Merck is accelerating the global clinical development of sac-TMT, both as a monotherapy and in combination with KEYTRUDA (pembrolizumab), across various solid tumors. There are currently ten ongoing Phase 3 studies involving sac-TMT. Among these, TroFuse-004 and TroFuse-009 are two prominent trials evaluating sac-TMT against chemotherapy in previously treated NSCLC patients with EGFR mutations or other genomic alterations.

Sac-TMT recently achieved its first marketing authorization in China for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC). This approval was based on results from the Phase 3 OptiTROP-Breast01 study. Kelun-Biotech retains the rights to develop, manufacture, and commercialize sac-TMT in Greater China under the collaboration agreement with Merck.

Sacituzumab tirumotecan (sac-TMT) consists of three main components: a TROP2-targeting monoclonal antibody (sacituzumab), a cytotoxic payload from the topoisomerase 1 inhibitor class, and a novel linker that connects the antibody to the cytotoxic payload using proprietary technology. TROP2 is highly expressed in various epithelial-derived tumors and is associated with tumor proliferation, invasion, and metastasis. TROP2 ADCs specifically target TROP2-expressing tumor cells to deliver their cytotoxic payload, showing promising anti-tumor activity in clinical trials.

Kelun-Biotech, a subsidiary of Kelun Pharmaceutical, developed sac-TMT. Merck has exclusive rights to develop, manufacture, and commercialize sac-TMT outside Greater China, while Kelun-Biotech focuses on its development within the region.

Lung cancer remains the leading cause of cancer-related deaths worldwide, with an estimated 2.4 million new cases and 1.8 million deaths in 2022. Non-small cell lung cancer (NSCLC) accounts for approximately 80% of all lung cancer cases. EGFR mutations are present in 14% to 38% of NSCLC tumors globally. While the five-year survival rate for lung cancer in the United States is improving, there remains a significant need for early detection and innovative treatments, as 44% of lung cancer cases are diagnosed at advanced stages.

Merck continues to focus on cancer research and development, striving to bring innovative treatments to patients, particularly those with unmet medical needs. The company’s commitment to advancing oncology is underpinned by a diverse pipeline of over 25 novel mechanisms and one of the largest clinical development programs across more than 30 tumor types. Through ongoing research and development, Merck aims to improve survival rates and quality of life for cancer patients worldwide.