On March 10, 2025 Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. (the "Company") reported that the Company’s trophoblast cell-surface antigen 2 (TROP2)-directed antibody-drug conjugate (ADC) sacituzumab tirumotecan (sac-TMT, formerly SKB264/MK-2870) was approved for marketing by the National Medical Products Administration (NMPA) for the second indication which is for the treatment of adult patients with epidermal growth factor receptor (EGFR) mutant-positive locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) following progression on EGFR-tyrosine kinase inhibitor (TKI) therapy and platinum-based chemotherapy (Press release, Kelun, MAR 10, 2025, View Source [SID1234651047]). This is the first TROP2 ADC drug approved for marketing in lung cancer globally. Compared with current standard of care, sac-TMT significantly extents the overall survival benefits of these patients.
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The approval is based on a multi-center, randomized, controlled, pivotal study (OptiTROP-Lung03) that evaluates the efficacy and safety profile of sac-TMT monotherapy 5mg/kg every other week (Q2W) as an intravenous injection versus docetaxel for the treatment of patients with locally advanced or metastatic EGFR-mutant NSCLC who have failed after treatment with an EGFR-TKI and platinum-based chemotherapy (used sequentially or in combination). As demonstrated in a pre-specified interim analysis, sac-TMT monotherapy demonstrated a statistically significant and clinically meaningful improvement in objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) compared with docetaxel.
Sac-TMT is also the first ADC drug to demonstrate a statistically and clinically significant improvement in overall survival benefit versus standard of care in patients with EGFR-mutant NSCLC after failure of EGFR-TKI and platinum-based chemotherapy.
Previously, the NMPA has approved the marketing of sac-TMT in China for 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 them for advanced or metastatic setting) and accepted a supplemental new drug application (sNDA) seeking the approval of sac-TMT monotherapy for patients with EGFR-mutant NSCLC who have failed after EGFR-TKI therapy.
Currently, sac-TMT is fully deployed in the NSCLC field, and Merck Sharp & Dohme and the company are conducting a total of 10 registrational Phase Ⅲ clinical studies in NSCLC globally and in China, with the threads covering from the late backline to early postoperative adjuvant, including monotherapy and combination studies. Among them, a registrational Phase Ⅲ clinical study has been conducted in China in combination with osimertinib for the first-line treatment of locally advanced or metastatic NSCLC with EGFR mutations (OptiTROP-Lung07).
Dr. Michael Ge, CEO of Kelun-Biotech said, "We are very pleased that the second indication of the Company’s TROP2 ADC sacituzumab tirumotecan has been approved for marketing, which is exciting progress for us in the field of lung cancer. The successful approval of this new indication will help to address an unmet treatment need for patients with later-stage EGFRm NSCLC in China. Kelun-Biotech has always been committed to promoting innovation and leadership, and we look forward to continuing our research in the field of ADCs in partnership with MSD."
About NSCLC
Lung cancer, the second most common cancer in the world, includes two main types of cancer: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC is the most common pathological type, accounting for about 80 to 85% of all lung cancers. The molecular typing of NSCLC patients in China is different from that of Western populations, and EGFR mutation is a common variant gene type, accounting for about 40 to 50% of lung adenocarcinoma patients in China. According to the 2024 Chinese Journal of Cancer Research (CSCO) guidelines, EGFR-TKIs are the preferred treatment for stage IV EGFR-mutant NSCLC.1 Platinum-containing chemotherapy is the main first-line chemotherapy regimen after resistance to EGFR-TKIs; and existing treatment regimens are ineffective in those who have failed EGFR-TKIs and platinum-containing chemotherapy. New drugs are urgently needed to improve patient survival.
About sac-TMT (佳泰莱)
Sac-TMT, a core product of the Company, is a novel human TROP2 ADC in which the Company has proprietary intellectual property rights, targeting advanced solid tumors such as NSCLC, breast cancer (BC), gastric cancer (GC), gynecological tumors, among others. Sac-TMT is developed with a novel linker to conjugate the payload, a belotecan-derivative topoisomerase I inhibitor with a drug-to-antibody-ratio (DAR) of 7.4. Sac-TMT specifically recognizes TROP2 on the surface of tumor cells by recombinant anti-TROP2 humanized monoclonal antibodies, which is then endocytosed by tumor cells and releases KL610023 intracellularly. KL610023, as a topoisomerase I inhibitor, induces DNA damage to tumor cells, which in turn leads to cell-cycle arrest and apoptosis. In addition, it also releases KL610023 in the tumor microenvironment. Given that KL610023 is membrane permeable, it can enable a bystander effect, or in other words kill adjacent tumor cells.
In May 2022, the Company licensed the exclusive rights to MSD (the tradename of Merck & Co., Inc., Rahway, NJ, USA) to develop, use, manufacture and commercialize sac-TMT in all territories outside of Greater China (includes Mainland China, Hong Kong, Macau, and Taiwan).