Phase 2 Trial Of S-531011 With RadScopal In Previously Treated Metastatic Colorectal Cancer

To learn if the experimental drug S-531011 plus RadScopalTM radiation therapy can help to control previously treated metastatic colorectal cancer.

Eligibility Criteria 1. Age ≥18 years 2. Histologically or cytologically confirmed non-MSI-H colorectal adenocarcinoma with metastatic or locally advanced unresectable disease. 3. Anticipated life expectancy greater than 3 months. 4. Prior receipt of fluoropyrimidine, oxaliplatin, and irinotecan as standard-of-care chemotherapy. 5. Presence of measurable disease per RECIST v1.1. 6. Participants must have at least two target lesions amenable to treatment with RadScopalTM XRT, with at least one lesion amenable to HD-XRT (50 Gy in 4 fractions or 30 Gy in 5 fractions) as determined by the treating radiation oncologist. Repeat radiation with LDXRT to previously irradiated sites will be allowed at the discretion of the treating radiation oncologist. 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 8. Adequate organ and marrow function as defined below: * Absolute neutrophil count ≥1,500/mcL * Hemoglobin ≥9 g/dL * Platelets ≥100,000/mcL * AST and ALT ≤3x institutional upper limit (ULN). If liver enzyme abnormalities are due to underlying liver metastases, AST and ALT ≤ 5x institutional ULN Total serum bilirubin \55 years of age * Postmenopausal women (as defined above) and \80% of total liver volume, as assessed by the investigator and/or treating radiation oncologist. 3. Prior XRT to the target lesion(s) selected for HD-XRT. 4. Prior organ or tissue allograft. 5. Presence or history of immunodeficiency that requires chronic use of systemic corticosteroids (≥ 10mg of prednisone equivalent per day) or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. 6. Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease-modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. 7. Any anticancer therapy within the past 4 weeks before enrollment. 8. Extended field radiation within the past 4 weeks or limited field radiation within the past 2 weeks before enrollment. 9. Participants who have not recovered from adverse events due to prior anticancer therapy (i.e. \>grade 2 residual toxicities) with the exception of alopecia and platinum-induced peripheral neuropathy. 10. Active brain metastases, unless adequately treated and participant is neurologically stable (except for residual symptoms of central nervous system treatment) for at least 2 weeks prior to enrollment without corticosteroids or are on a stable or decreasing dose of ≤10 mg daily prednisone (or equivalent). 11. Presence of symptomatic leptomeningeal disease. 12. Clinically significant cardiac, respiratory, or other medical or psychiatric conditions that might interfere with participation in the trial or interfere with the interpretation of trial results, in the opinion of the investigator. 13. Pregnant women are excluded from this study because S-531011 is an agent with the potential for teratogenic or abortifacient effects.