What question did this study set out to answer?

The research aims to evaluate the antitumor efficacy and pharmacokinetic properties of DXC016, a novel cMET-targeting ADC.

April 5, 2026

Abstract 2393: DXC016, a novel cMET-targeting dual payload antibody-drug conjugate, demonstrates potent antitumor activity and favorable PK for potential subcutaneous use.

Key Points

The research aims to evaluate the antitumor efficacy and pharmacokinetic properties of DXC016, a novel cMET-targeting ADC.
Evaluated in vitro and in vivo antitumor activity across various cMET-expressing tumor models.
Conducted pharmacokinetic studies in mice assessing subcutaneous absorption.
Preliminary safety studies with repeated dosing in rats and monkeys.
DXC016 showed potent antitumor activity with tumor regression at doses below 1.5 mg/kg.
Outperformed benchmark ADCs in multiple cancer models.
Improved pharmacokinetics with enhanced absorption noted with co-administration of DXE001.
Demonstrated a favorable safety profile with no treatment-related mortality in animal studies.

Abstract

Abstract 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. Citation Format: Yong Du, Jiaojiao Yu, Huihui Guo, Lingli Zhang, Xiaoqiang Xie, Jialei Hu, Xiafen Wu, Yunxia Zheng, Yuanyuan Huang, Junxiang Jia, Wei Liu, Zhouyang Zhou, Qingliang Yang, Robert Y. Zhao. DXC016, a novel cMET-targeting dual payload antibody-drug conjugate, demonstrates potent antitumor activity and favorable PK for potential subcutaneous use abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2393.

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Abstract 2393: DXC016, a novel cMET-targeting dual payload antibody-drug conjugate, demonstrates potent antitumor activity and favorable PK for potential subcutaneous use.

Key Points

Abstract

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