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

Background: Integrin alpha-2 (ITGA2), a component of the heterodimeric transmembrane receptor integrin alpha2/beta1, 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: • Phase Ia (dose escalation with backfills) is to determine the maximum tolerated dose and the pharmacologically active dose range. A Bayesian Optimal Interval design will be used for dose escalation. • Phase Ib (dose optimisation) evaluates the optimal dosing regimen by assessing safety and preliminary anti-tumor activity at dose levels of interest.Approximately 102 participants will receive IPN60300 in phase I in the US, France and Spain. Based on results from phase I, a phase II dose expansion study will be included via protocol amendment. Enrolment for Phase Ia is ongoing. Clinical trial information: NCT07213817