Phase 1b Dose Escalation Study of Intravenous JX-594 in Metastatic, Refractory Colorectal Carcinoma

This is a Phase Ib, open-label, dose-escalation study designed to evaluate the safety and tolerability of Pexa-Vec (JX-594), a vaccinia GM-CSF/thymidine kinase-deactivated virus, administered intravenously in patients with advanced/metastatic colorectal carcinoma (CRC) that is refractory to standard therapy. Vaccinia virus, from which Pexa-Vec is derived, shows a natural selectivity toward cancer relative to normal tissues after intravenous (IV) administration. The study utilizes a sequential dose-escalating design to determine the maximum tolerated dose (MTD) and/or maximum feasible dose (MFD). Patients will receive 4 biweekly treatments of Pexa-Vec administered by IV infusion over 60 minutes on Days 1, 15, 29, and 43. Patients will be sequentially enrolled into one of three dose cohorts: * Cohort 1: 1 × 10\^6 pfu/kg * Cohort 2: 1 × 10\^7 pfu/kg * Cohort 3: 3 × 10\^7 pfu/kg Three patients will be treated at each dose level unless a dose-limiting toxicity (DLT) is observed, at which point the cohort may be expanded. All patients will receive hydration and will be observed in the clinic and/or hospital for a minimum of 24 hours after each infusion. In addition to safety endpoints, secondary objectives include the evaluation of Pexa-Vec pharmacokinetics (PK), pharmacodynamics, immune response, and preliminary anti-tumoral activity. Tumor response assessments will be conducted using CT or MRI on Days 29 and 57 (±2 days) based on Response Evaluation Criteria in Solid Tumors (RECIST).