Sichuan Kelun Pharmaceutical (002422.SZ): The Phase III clinical study on the first-line treatment of locally advanced or metastatic PD-L1 negative non-squamous non-small cell lung cancer with sacituzumab govitecan (sac-TMT) in combination with pembrolizumab has achieved its primary endpoint.

Sichuan Kelun Pharmaceutical (002422.SZ) announced that its holding subsidiary, Kelun Bote, in collaboration with Merck, has achieved the primary endpoint of progression-free survival (PFS) in the phase III clinical study (OptiTROP-Lung06) of the antibody-drug conjugate (ADC) sacituzumab govitecan (sac-TMT) combined with pembrolizumab for the first-line treatment of locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) that is negative for programmed death-ligand 1 (PD-L1) in the interim analysis of the study conducted by the Independent Data Monitoring Committee (IDMC). This is the world's first phase III clinical study to achieve the primary endpoint in first-line treatment of driver gene negative and PD-L1 negative non-squamous NSCLC with a combination of ADC and immune checkpoint inhibitors. As a core product of Kelun Bote, sacituzumab govitecan (sac-TMT) is a novel TROP2ADC with independent intellectual property rights owned by Kelun Bote, targeted at late-stage solid tumors such as NSCLC, breast cancer (BC), gastric cancer (GC), gynecological tumors, and genitourinary tumors. sacituzumab govitecan (sac-TMT) is developed using a unique bifunctional linker. The linker irreversibly binds with the anti-TROP2 monoclonal antibody sacituzumab forming a bond, and can effectively deliver the payload, a pH-sensitive cleavable topoisomerase I inhibitor derivative of SN-38, to tumor cells in the lysosome, achieving a drug antibody ratio (DAR) of 7.4. sacituzumab govitecan (sac-TMT) specifically recognizes TROP2 on the surface of tumor cells through a recombinant anti-TROP2 humanized monoclonal antibody, is then internalized by the tumor cells, and releases the payload KL610023 intracellularly. KL610023, as a topoisomerase I inhibitor, induces DNA damage in tumor cells, leading to cell cycle arrest and apoptosis. Additionally, it also releases KL610023 in the tumor microenvironment. Due to the cell membrane permeability of KL610023, bystander effects can be achieved, killing neighboring tumor cells.