DXC016：一种新型cMET靶向双载荷抗体偶联药物，展现出强效抗肿瘤活性和有利于皮下给药的药代动力学

DXC016 is a next-generation cMET-targeting antibody-drug conjugate (ADC), composed of a novel anti-cMET monoclonal antibody (DXA016) and a functional dual payload designed to overcome limitations of conventional cMET-ADCs. Across multiple cMET-expressing tumor models, including SNU-5 (gastric), EBC-1 (NSCLC), HCT116 (colorectal), SW1990 (pancreatic), and an osimertinib-resistant NSCLC model, DXC016 demonstrated potent in vitro and in vivo antitumor activity, archived tumor regression at doses below 1.5 mg/kg and outperformed DXd and MMAE-based benchmark ADCs, highlighting the superior efficacy enabled by the dual-payload design. In mouse subcutaneous pharmacokinetic studies, co-administration with the recombinant hyaluronidase DXE001 markedly accelerated absorption, as indicated by a substantially earlier Tmax, while overall exposure remained similar between groups due to the thin and low-resistance subcutaneous tissue in mice. Given the higher hyaluronan content and greater diffusional resistance in human skin, DXE001 is expected to produce a more pronounced enhancement of subcutaneous absorption and bioavailability in clinical settings. In preliminary safety studies in rats and cynomolgus monkeys with once-weekly dosing for three administrations, DXC016 was well tolerated up to 80 mg/kg in rats and 50 mg/kg in monkeys, with no treatment-related mortality observed, indicating a favorable early safety profile. Collectively, the strong antitumor efficacy, improved subcutaneous absorption profile with DXE001, and encouraging preliminary safety characteristics support DXC016 as a promising clinical development candidate of next-generation cMET-targeting ADC.