Phase 1/2, Multicenter, Non-Randomized, Open-Label, Multiple-Dose First-In-Human Study Of U3-1402 (Anti-Her3 Antibody Drug Conjugate) In Subjects With Her3-Positive Metastatic Breast Cancer

TPS1116Background: There is a need for effective late-line treatments in metastatic breast cancer. HER3 overexpression in breast cancer is associated with poor prognosis, but there is as yet no approved targeted treatment against HER3. U3-1402 is a novel antibody-drug conjugate (ADC) comprised of a fully humanized anti-HER3 antibody (patritumab) covalently conjugated via a cleavable peptide linker to a derivative of the topoisomerase I inhibitor exatecan. After U3-1402 binds to HER3 on the tumor cell surface, it is internalized and leads to apoptosis via inhibition of topoisomerase I. This ADC achieves a high drug-to-antibody ratio of ~8:1. Methods: This is a Phase 1/2, multicenter, non-randomized, open-label, multiple-dose, first-in-human study in subjects with HER3-positive metastatic breast cancer. The study consists of 3 parts: Dose Escalation, Dose Finding, and Phase 2. In Dose Escalation, safety and tolerability of U3-1402 are evaluated and the maximum tolerated dose is determined using the modified...