BAL/BOT/agenT-797 in pMMR CRC With Liver Metastases

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