Leronlimab (CCR5 mAb) + TAS-102/Bev shows early ctDNA drops and 100% stable disease in refractory mCRC (CLOVER)

Leronlimab (LRM) is a subcutaneous anti-CCR5 humanized monoclonal antibody being added to the current late-line standard regimen trifluridine/tipiracil (TAS-102) plus bevacizumab in the open-label Phase 2 CLOVER study (NCT06699836) for CCR5+ refractory mCRC. As of abstract drafting, 23/37 (62.2%) screened patients were enrolled; no LRM-related dose-limiting toxicities were seen at 350mg, and 700mg dosing had started, with early efficacy in 6 centrally imaged patients showing stable disease in 6/6 (median tumor-size change -10.2%, range +12.5% to -28.4%) and ctDNA declines by Week 2 (n=11; median -85%, range -9% to -99%). With TAS-102/Bev alone (Phase 3 SUNLIGHT), the benchmark is modest tumor shrinkage/very low ORR but improved survival (mOS 10.8mo vs 7.5mo for TAS-102; mPFS 5.6mo vs 2.4mo), so CLOVER’s early “all-SD” signal is directionally consistent with expected disease control—however, it’s too early (n=6 imaged) to claim additive clinical benefit beyond the TAS-102/Bev backbone, and the PD-L1 increases on CTCs/CAMLs (12/17, 70.6% by Week 5) remain hypothesis-generating.