Immune Response Activation for the Treatment of Unresectable Metastatic Colorectal Cancer or CEA Positive Metastatic Breast Cancer

PRIMARY OBJECTIVE: I. Identify the maximum tolerated dose (MTD) and recommend phase 2 dose (RP2D) and characterize toxicities associated with administration of the M5A-IL2 after fractionated SBRT. SECONDARY OBJECTIVES: I. Describe the therapeutic response to treatment of irradiated and unirradiated tumors per Criteria in Solid Tumors version 1.1 (RECIST v 1.1) guidelines. II. Describe AEs by M5A-IL2 dose level, per Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0. III. Describe the pharmacokinetics of M5A-IL2. IV. Describe the frequency of auto-antibody formation, overall and by dose of M5A-IL2. EXPLORATORY OBJECTIVE: I. If medically feasible, tumors targeted for SBRT will be biopsied pre-SBRT and 1-2 weeks post 3rd dose of M5A-IL2. OUTLINE: This is a dose-escalation study of M5A-ICK. Patients undergo SOC SBRT over 3 fractions on days 1, 3, and 5, followed by M5A-ICK subcutaneously (SC) on days 8, 9, and 10 once daily for a single cycle on study. Patients undergo computed tomography (CT) or positron emission tomography (PET)/CT as well as blood sample collection throughout the trial. Patients may undergo magnetic resonance imaging or bone scan as clinically indicated on the trial. Additionally, patients may optionally undergo tissue biopsy during screening and on study. After completion of study treatment, patients are followed-up at 3 months.