ARC-101: An Investigational CLDN6-Targeted Bispecific T-Cell Engager for Solid Tumors

1. Executive Summary

ARC-101 is an investigational bispecific T-cell engaging (TCE) antibody developed by Third Arc Bio Inc., currently undergoing Phase 1 clinical evaluation for the treatment of Claudin 6 (CLDN6)-positive solid tumors.[1] The molecule is designed to dually target CLDN6, an oncofetal antigen predominantly expressed on tumor cells, and the CD3 epsilon (CD3ε) component of the T-cell receptor complex on T-lymphocytes.[3] This engagement aims to redirect cytotoxic T-cells to mediate the lysis of CLDN6-expressing cancer cells. Preclinical studies have highlighted ARC-101's high specificity for CLDN6, potent cytolytic activity, a long pharmacokinetic half-life, and optimal biophysical properties, positioning it as a potential best-in-class therapeutic agent.[1]

The selection of CLDN6 as a target is based on its highly restricted expression profile, being largely absent in normal adult tissues but frequently re-expressed in various malignancies, including ovarian and testicular cancers.[3] This differential expression is anticipated to provide a favorable therapeutic window. The ongoing first-in-human Phase 1 clinical trial (NCT06672185; ARC101-P1-101) is evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of ARC-101 in patients with advanced CLDN6-expressing solid tumors.[2]