Abstract A014: CAN020, a Trop2-targeting, dual-payload ADC from CanWell Pharma

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Abstract ADCs targeting Trop2 such as sacituzumab govitecan and Dato-DXd have become standard-of-care treatments for TNBC and NSCLC though are limited by resistance and their adverse event profiles including grade 3/4 neutropenia, high (>50%) rates of stomatitis/mucositis, and an increased risk of interstitial lung disease. To address these challenges, CanWell Pharma has developed CAN020, a TROP2-targeting ADC bearing two payloads having distinct mechanisms of action: a topoisomerase I inhibitor (TOP1i) and a PARP inhibitor (PARPi), installed via a cleavable linker based on CanWell’s StarLinker technology. In in vitro and in vivo studies, the affinity and internalization of CAN020 were confirmed similarly with its antibody. CAN020-induced cytotoxicity outperformed its corresponding mono-payload ADCs, findings consistent with in vitro studies which found that its PARPi payload synergistically enhanced the antiproliferative effect of its TOP1i payload. In animal studies, CAN020 demonstrated efficacy across several Trop2-expressing CDX models including human breast, ovarian, and gastric tumors, in which exhibited strong antitumoral growth inhibition over Standard of Care ADCs and its single payload ADCs. CAN020 was well tolerated in CDX models up to the highest tested dose. Collectively, these results support CAN020 as a clinical candidate and its advancement to Phase I clinical trials. Citation Format: Shaoshan Wang, Pengqi Xu, Sanlong Wang, Yili Yang, Ya Luo, Yichi Chen, Wanping Geng, Weihao Li, Liying Li, Zihao Wu, Xianyang Chen, Henry Ninghui Yu. CAN020, a Trop2-targeting, dual-payload ADC from CanWell Pharma [abstract]. In: Proceedings of AACR Drug Discovery and Development (AACR D3) Conference; 2026 Jul 21-24; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(14_Suppl):Abstract nr A014.

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