Phase 2 S-531011 CCR8-directed monoclonal antibody plus RadScopal radiation in MSS mCRC.

This Phase 2 MD Anderson Cancer Center study tests whether S-531011 (a CCR8-directed monoclonal antibody designed to modulate CCR8+ immune cells in the tumor microenvironment) can work better when paired with RadScopalTM high-dose radiation therapy (HD-XRT) in previously treated, unresectable locally advanced/metastatic colorectal adenocarcinoma that is non–MSI-high (i.e., typical MSS disease). The trial uses an investigational/expansion-style treatment group in which patients receive IV S-531011 plus localized radiation intended to drive systemic immune effects (“abscopal” concept) beyond the irradiated lesion. The scientific angle is combining a targeted immunomodulator (anti-CCR8) with radiation as an in situ “immune primer” to potentially overcome the well-known checkpoint-resistant biology of MSS metastatic CRC. Today’s care after progression is sequential systemic options such as chemotherapy re-challenge, anti-VEGF therapy, EGFR antibodies for RAS/RAF wild-type left-sided tumors, and later-line agents like regorafenib or trifluridine/tipiracil, with immunotherapy mainly benefiting the MSI-high minority.