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