CCR5 Targeting Leronlimab in Combination With Hepatic Arterial Infusion Floxuridine and Systemic Therapy for the Treatment of Colorectal Cancer Liver Metastases, CHAMP Trial

PRIMARY OBJECTIVE: I. To evaluate the feasibility of administering four planned cycles of combined standard-of-care systemic therapy, hepatic arterial infusion (HAI) floxuridine (FUDR), and leronlimab as reflected by relative dose intensity in the study population. SECONDARY OBJECTIVES: I. To characterize the safety profile of the combined regimen. II. To evaluate the anti-tumor activity of leronlimab administered subcutaneously alongside HAI pump and systemic therapy in patients with colorectal cancer with liver metastases, as assessed by 1 year and 2 year progression-free survival (PFS) and median progression free-survival. III. To evaluate liver-specific disease control with leronlimab plus HAI pump and systemic therapy. IV. To evaluate the anti-tumor activity of Leronlimab administered subcutaneously alongside HAI pump and systemic therapy in patients with colorectal cancer with liver metastases, as assessed by changes in circulating tumor deoxyribonucleic acid (DNA) (ctDNA) and ctDNA clearance. EXPLORATORY OBJECTIVES: I. To characterize baseline and on-treatment tissue and circulatory biomarkers of immune evasion and metastatic potential, including PD-L1 expression, immune genomic and phenotypic biomarkers, and circulating tumor cells. II. To assess liver damage and healing associated with leronlimab plus HAI pump and systemic therapy. III. To evaluate standard-of-care imaging findings and liver parenchyma for evidence of liver damage and disease progression. OUTLINE: Patients receive leronlimab subcutaneously (SC) weekly with SOC systemic therapy for up to 6 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo surgical resection with HAI pump placement. Starting 4 weeks after surgery, patients receive floxuridine continuously via HAI pump every 14 days of each cycle and resume leronlimab SC weekly in combination with SOC systemic therapy of each cycle. Cycles repeat every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and computed tomography (CT) and/or magnetic resonance imaging (MRI) throughout the study. Additionally, patients may optionally undergo biopsy on study. After completion of study treatment, patients are followed up at 30 days and then for up to 24 months.