Merck has recently added a new open-label Phase II clinical study, MK-2010-003, to its pipeline. This trial evaluates the combination of the TROP2 ADC sac-TMT (Jia Tai Lai®) with the PD-1/VEGF bispecific antibody MK-2010 in patients with advanced solid tumors. The study is currently in the start-up phase at the "St. Gallen, Bellinzona" research center in Switzerland.
Sac-TMT is a novel TROP2 ADC developed by SKB BIO with independent intellectual property rights. It is being investigated for advanced solid tumors, including non-small cell lung cancer (NSCLC), breast cancer (BC), gastric cancer (GC), and gynecological and urogenital tumors. The drug is developed using a unique dual-functional linker, forming an irreversible bond with the anti-TROP2 antibody while also being pH-sensitive for cleavage, maximizing payload delivery to tumor cells with a drug-to-antibody ratio (DAR) of 7.4.
The drug specifically recognizes TROP2 on tumor cell surfaces, is internalized, and releases the payload KL610023 intracellularly. As a topoisomerase I inhibitor, KL610023 induces DNA damage in tumor cells, leading to cell cycle arrest and apoptosis. It also releases into the tumor microenvironment, and due to its cell membrane permeability, it can achieve a bystander effect, killing neighboring tumor cells.
In May 2022, SKB BIO granted Merck exclusive rights to develop, use, manufacture, and commercialize sac-TMT outside of Greater China (including Mainland China, Hong Kong, Macau, and Taiwan). Currently, Merck has initiated 17 global Phase III clinical studies for its core product sac-TMT, the highest number among its ADC pipeline, reflecting strong recognition of this Chinese innovative drug and deep collaboration.
Notably, one of these studies, the global Phase III TroFuse-005 trial for specific advanced or recurrent endometrial cancer, achieved dual primary endpoints of overall survival (OS) and progression-free survival (PFS) in May this year, adding solid evidence for the drug's clinical value. The newly launched MK-2010-003 study uses sac-TMT and the PD-1/VEGF bispecific antibody MK-2010 as experimental drugs to explore the efficacy and safety of this combination in solid tumor patients.
This powerful combination underscores Merck's strong belief in the therapeutic potential of sac-TMT and MK-2010. This "ADC+IO 2.0" model could potentially lead the next wave of innovation in cancer treatment. From a deeper perspective, the combination of sac-TMT and MK-2010 has a scientific synergistic rationale. Previous studies of sac-TMT combined with PD-(L)1 inhibitors like pembrolizumab (e.g., OptiTROP-Lung05) have yielded positive data, validating the "ADC+IO" model. The PD-1/VEGF bispecific antibody, by adding anti-angiogenic effects on top of PD-(L)1 inhibition, can alter the tumor vasculature by modulating angiogenesis and vascular permeability. This promotes ADC penetration and exposure to tumor cells, enhancing its anti-tumor activity.
Merck's rapid positioning in the "ADC+IO 2.0" bispecific antibody combination track is not only a key move in its global R&D strategy but also marks the accelerated integration of China's innovative ADC drugs into the mainstream international treatment system. Sac-TMT, as a flagship product of SKB BIO, has leveraged the "sailing on a big ship" model to become a core asset in Merck's pipeline. As more global clinical data emerges, this innovative molecule originating from China could offer breakthrough treatment options for patients with advanced solid tumors worldwide, while also writing a new chapter in the globalization of Chinese innovative drugs.
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