TPS277 Background: Effective treatment for patients with metastatic colorectal cancer (mCRC) who have progressed on first-line therapy remains a significant unmet clinical need. BOLD-100 is a novel, first-in-class ruthenium-based anticancer therapeutic that has a unique, multimodal mechanism of action to kill cancer cells. Unlike traditional chemotherapy drugs that often target a single pathway, BOLD-100 works in several ways to overcome drug resistance and induce cell death, making it particularly effective when used in combination with other anticancer therapies. Data from the initial Phase 1/2 study of BOLD-100 plus FOLFOX (NCT04421820) indicated promising antitumor activity and well tolerated safety profile in patients with refractory mCRC (O'Kane, G. M. , et al. Annals of Oncology 35 (2024): S22. ). In addition, there was an unexpected reduction in oxaliplatin-induced peripheral neuropathy (OIPN) even in previously treated oxaliplatin patients. The efficacy and safety profile of this combination boosts its potential clinical benefit (Kumar, Ashish, et al. Abstract LB432: Cancer Research 85. 8Supplement₂ (2025) ). Herein, we describe a phase 2 study comparing BOLD-100 plus FOLFOX with standard of care (FOLFOX) for the 2L treatment of patients with mCRC. Methods: BOLD-100-001 (NCT04421820) is a prospective, open-label, randomized global phase 2 study in patients with metastatic adenocarcinoma of the colon/rectum with measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1. 1, ECOG performance status 0–1 and BRAF wildtype tumor status. Patients must have received only 1 prior line of treatment in the metastatic setting. Prior oxaliplatin is permitted if: 1) received in the adjuvant setting; 2) received in first line setting with no progression on treatment or within 3 months of oxaliplatin treatment cessation. Concurrent treatment with monoclonal antibody therapy (anti-EGFR, anti-VEGF, or anti-HER2) is not allowed. Patients will be randomized 1: 1: 1 to one of three cohorts: BOLD-100 at 500 mg/m² plus FOLFOX (Cohort 1), BOLD-100 at 625 mg/m² plus FOLFOX (Cohort 2), or FOLFOX alone (Cohort 3) and stratified by tumor sidedness (left vs right), KRAS mutation status (wild-type vs mutant), and geographical region (South Korea vs other). Primary objectives are to evaluate progression-free survival (PFS), overall survival (OS), and overall response rate (ORR) by RECIST v1. 1. Secondary safety objectives include evaluations of adverse event data, vital signs, and clinical laboratory testing. Exploratory objectives include assessment of duration of response (DOR), changes in biomarkers, and health-related quality of life and neuropathy-related quality of life per EORTC-QLQ-30 and EORTC-QLQ-CIPN20 scores. 120 patients are expected to be enrolled. Enrollment is ongoing at sites in Canada, South Korea and Europe. Clinical trial information: NCT04421820.
O'Kane et al. (Sat,) studied this question.