Preliminary results of a phase 2 study of leronlimab in combination with TAS-102 and bevacizumab in previously treated metastatic colorectal cancer

Background: CCR5 promotes recruitment of immunosuppressive myeloid populations and contributes to immune evasion in metastatic colorectal cancer (mCRC). Leronlimab is a humanized monoclonal antibody targeting CCR5 with immune-activating effects. TAS-102 plus bevacizumab is a standard regimen in refractory mCRC. This study evaluates the safety of leronlimab in combination with TAS-102/bevacizumab and if this combination enhances objective response rates via immune activation. Methods: This ongoing multicenter Phase 2 trial will enroll up to 60 previously treated mCRC patients. Leronlimab will be initially dosed 350 mg SC QW with TAS-102/bevacizumab at standard doses. CCR5 expression and PD-L1 CPS is assessed by immunohistochemistry on tumor samples at baseline. PD-L1 and CCR5 is assessed in circulating tumor cells (CTCs) and cancer associated macrophage-like cells (CAMLs) from blood samples. Results: Among all pre-screened patients with evaluable archival samples, 33/33 (100%) demonstrated CCR5 expression. As of 11/17/ 2025, 10 patients have been enrolled across 6 sites, with preliminary baseline and biomarker data in Table 1. At the City of Hope site, 4/4 patients (with data) had clinical and/or biomarker responses, i.e. declines in CEA, CA19-9, and/or ctDNA, despite refractory liver-metastatic disease. Serial kinetics showed an increase in PD-L1 on CTCs and CAMLs after 1 week on treatment, while the number of CAMLs and CTCs lowered in responders. Leronlimab has been well tolerated, with no unexpected safety signals. This preliminary trial report, which is enrolling ahead of pace, reflects a high unmet need in mCRC disease. Conclusions: Leronlimab combined with TAS-102 and bevacizumab is feasible, showing promising early biomarker and clinical activity in heavily pretreated mCRC. Universal CCR5 positivity supports CCR5 as a potential therapeutic target. Updated outcomes and correlative data will be presented. Table Parameter Result Ethnicity (N=10) Hispanic n=1; Non-Hispanic n=9 Sex (N=10) Male n=6; Female n=4 Mean age (N=10) 54.3 years Mean weight (N=10) 100.2 kg CTCs at baseline: median (range)* 0 (0-2) CAMLs at baseline: median (range)* 47 (1-67) CTCs at follow-up: median (range)* 0 (0-4) CAMLs at follow-up: median (range)* 31 (1-87) PD-L1 increase in CAMLs or CTCs* 60% (n=3/5) * 5 patients with both baseline and Week 1 data