Abstract Background: Integrin alpha-2 (ITGA2), a component of the heterodimeric transmembrane receptor integrin α2/β1, plays a key role in cell adhesion and transduction. Although ITGA2 is expressed at low levels across normal tissues, it is notably overexpressed in various solid tumors, including pancreatic, gastric and colorectal, where it contributes to tumor progression via extracellular matrix signaling and epithelial-mesenchymal transition. IPN60300, a novel antibody-drug conjugate (ADC) targeting ITGA2, is designed to specifically deliver exatecan, a potent topoisomerase I inhibitor, to ITGA2 expressing cancer cells. IPN60300 consists of a humanized Fc mutated monoclonal antibody site-specifically conjugated to exatecan via a cathepsin-cleavable linker, with a drug-to-antibody ratio of 8. Preclinical studies of IPN60300 showed strong specific binding to ITGA2, enhanced internalization, intracellular release of bystander-active payload, significant tumor growth inhibition across various murine cancer models, a favorable pharmacokinetic (PK) profile, and an acceptable safety profile consistent with the known safety profile of other ADCs that have exatecan (or its derivatives) as payload. Methods: This is an open label, multicentre, phase I/II first-in-human (FIH), dose escalation, dose optimization, and dose expansion study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity and anti-tumor activity of IPN60300 as a single agent. Eligible adult participants should have a confirmed diagnosis of selected advanced gastrointestinal tumors (biliary track cancer, pancreatic cancer, colorectal cancer, gastric cancer and oesophageal cancer) for whom relapsed, refractory or progressive disease and no standard treatment exists. Phase I will be conducted as follows: Clinical trial information: NCT07213817 Citation Format: Manish R. Sharma, Jiyan Zou, Benjamin Beaufils, Aurelie Courtin, Sophie Colombo, Lineu Domit, Xiaofeng Shi, Elisabetta Leo, Shubham Pant. Phase I/II FIH study of IPN60300, a first-in-class ADC targeting ITGA2, to assess the safety, tolerability, PK, biomarkers, immunogenicity and antitumor activity in adults with locally advanced solid tumors abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86 (8Suppl): Abstract nr CT087.
Sharma et al. (Fri,) studied this question.