Radiation plus drug cocktail targets tough colorectal cancer

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Age 18 to 75 years (inclusive). Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. Histologically or cytologically confirmed colorectal cancer with unresectable metastatic or recurrent lesions. Has received at least first- and second-line systemic anti-tumor therapy for metastatic colorectal cancer (chemotherapy regimens may include fluoropyrimidines, oxaliplatin, irinotecan, with or without targeted agents such as bevacizumab or cetuximab) and has progressed after second-line therapy. Has evaluable lung or liver metastases amenable to stereotactic body radiotherapy (SBRT). Has at least one measurable lesion according to RECIST v1.1. Female patients of childbearing potential must have a negative urine or serum pregnancy test within ≤7 days before first dose of study drug. All fertile patients must agree to use highly effective contraception during the study and for ≥120 days after the last dose. Willing and able to provide written informed consent. Exclusion Criteria: * Laboratory abnormalities: absolute neutrophil count \<1.5×10⁹/L, platelet count \<100×10⁹/L, hemoglobin \<9 g/dL; total bilirubin \>1.5× upper limit of normal (ULN) (\>2.5× ULN for patients with liver metastases); AST/ALT \>2.5× ULN (\>5× ULN for patients with liver metastases); serum creatinine \>1.5× ULN or creatinine clearance \<60 mL/min; APTT or PT \>1.5× ULN; albumin \<30 g/L; clinically significant electrolyte abnormalities. Transfusion or growth factor support within 2 weeks before enrollment to meet eligibility is not permitted. Prior evidence of deficient mismatch repair (dMMR), microsatellite instability-high (MSI-H), or BRAF mutation by histology or ctDNA testing. Prior immunotherapy (anti-PD-1, anti-PD-L1, anti-CTLA-4, or any cellular immunotherapy). Active or history of autoimmune disease that may relapse. Requires systemic corticosteroids (\>10 mg/day prednisone equivalent) or other immunosuppressive drugs within 14 days before first dose of study drug (exceptions allowed for low-dose steroids, topical/inhaled steroids, or short-term prophylaxis). History of interstitial lung disease, non-infectious pneumonitis, pulmonary fibrosis, acute lung disease, or poorly controlled systemic disease (e.g., diabetes, hypertension). Clinically uncontrolled diarrhea. Severe chronic or active infection requiring systemic antimicrobial therapy, including tuberculosis. Brain or leptomeningeal metastases. Clinically significant pleural effusion, pericardial effusion, or ascites requiring repeated drainage within 2 weeks before first dose. Presence of clinically detectable second primary malignancy or other malignancy within the past 5 years (except adequately treated basal cell carcinoma of the skin or cervical carcinoma in situ). Poorly controlled diabetes or electrolyte disturbances despite standard medical management. Known HIV infection. Untreated chronic hepatitis B (HBV DNA \>500 IU/mL) or detectable hepatitis C virus (HCV) RNA. Inactive HBsAg carriers, treated and stable hepatitis B (HBV DNA ≤500 IU/mL), and cured hepatitis C are allowed. Major surgery within ≤28 days before first dose. Prior allogeneic stem cell or organ transplantation. Uncontrolled hypertension (systolic ≥140 mmHg or diastolic \>90 mmHg on monotherapy). Active gastrointestinal diseases (e.g., duodenal ulcer, ulcerative colitis, intestinal obstruction) or history of intestinal perforation/fistula not fully healed after surgery. History of arterial or deep vein thrombosis within 6 months before enrollment, or bleeding tendency/bleeding history within 2 months before enrollment regardless of severity. Stroke or transient ischemic attack within 12 months before enrollment; non-healing skin wound, surgical site, trauma, severe mucosal ulcer, or fracture; acute myocardial infarction, severe/unstable angina, or coronary artery bypass graft within 6 months; New York Heart Association (NYHA) class ≥2 heart failure. Severe hypersensitivity to other monoclonal antibodies, trifluridine/tipiracil, or any excipient. Received systemic chemotherapy within 28 days before first dose, or immunotherapy/hormonal therapy/targeted therapy/investigational therapy within 14 days or 5 half-lives (whichever is shorter). Received Chinese herbal medicine or proprietary Chinese medicine for cancer control within 14 days before first dose. Toxicities from prior anticancer therapy not recovered to baseline or stable level (except alopecia, neuropathy, and specific laboratory abnormalities deemed not a safety risk). Received live vaccine within 4 weeks before first dose. Any clinical or laboratory abnormality or compliance issue that, in the investigator's judgment, makes the patient unsuitable for the study. Severe psychological or mental abnormalities.