New triple therapy takes on 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: * Adults ≥18 years of age with histologically confirmed metastatic colorectal cancer with liver metastases, including evidence of active liver disease if previously treated locally * At least one measurable lesion per RECIST v1.1, with ≥1 target lesion in the liver * Tumor confirmed as microsatellite stable (MSS)/proficient mismatch repair (pMMR) per a FDA-approved assay (Caris MI Cancer Seek®, FoundationOne® CDx, or Tempus xT CDx). * Received ≥1 prior line of systemic therapy including fluorouracil, oxaliplatin, and irinotecan (not necessarily in combination), and prior EGFR inhibitor or bevacizumab if eligible, unless contraindicated * ECOG performance status 0-1 and life expectancy ≥12 weeks * Adequate organ and marrow function: * ANC ≥1.5 × 10⁹/L * Platelets ≥100 × 10⁹/L * Hemoglobin ≥ 9 g/dL * AST/ALT ≤2.5 × ULN * Total bilirubin ≤1.5 × ULN * Creatinine clearance ≥ 40 mL/min, as measured or calculated per local institutional standards. * Albumin ≥3 g/dL * PT/PTT ≤1.5 × ULN * Willing and able to provide written informed consent * Negative pregnancy test for women of childbearing potential * Agreement to use effective contraception during study participation Exclusion Criteria: * Tumor is dMMR/MSI-high * Prior treatment with PD-1, PD-L1, CTLA-4 inhibitors, or other immunotherapy agents * Evidence of bowel obstruction, impending obstruction, or recent obstruction (within 3 months) * Refractory ascites requiring frequent paracentesis or recent escalation of diuretics * Clinically significant cardiovascular disease (e.g., recent myocardial infarction or stroke, unstable angina, NYHA class ≥III heart failure, uncontrolled arrhythmias) or QTc \>480 ms * Active or untreated brain metastases or leptomeningeal disease * Concurrent malignancy requiring treatment or active within 2 years (with protocol-specified exceptions) * Receipt of prior anti-cancer therapy within protocol-defined washout periods, including: * Cytotoxic, targeted therapy or other investigational therapy within 3 weeks. * Monoclonal antibodies, antibody-drug conjugates, radioimmunoconjugates, or similar therapy, within 4 weeks, or 5 half-lives, whichever is shorter. * Small molecules/tyrosine kinase inhibitors within 2 weeks or less than 5 circulating half-lives of investigational drug. * Known hypersensitivity to study drugs or excipients * History of or active interstitial lung disease or pneumonitis requiring systemic steroids * Prior allogeneic transplant (organ, stem cell, or bone marrow) * Active or recent autoimmune disease requiring systemic treatment * Requirement for systemic corticosteroids (\>10 mg prednisone equivalent) or other immunosuppressive therapy within defined windows * Active infection, including HIV, HTLV, HBV, HCV, or other infections requiring systemic therapy * Recent SARS-CoV-2 infection within protocol-defined timeframe * Uncontrolled hypertension, significant proteinuria (UPCR ≥1 g/g), or other clinically significant uncontrolled medical conditions * Non-healing wounds, active bleeding, or uncontrolled thyroid dysfunction * Psychiatric or substance use disorders that may interfere with study participation * Receipt of live or attenuated vaccines within 30 days prior to treatment and while participating in the study * Pregnant or breastfeeding women, or those planning pregnancy during the study