A Pilot Study of Botensilimab and Balstilimab and SBRT in Non-MSI-H or pMMR Colorectal Cancer With Liver Metastasis
This is a single-arm pilot feasibility study evaluating the combination of Botensilimab and Balstilimab with Radiation Therapy (RT) in Non-Microsatellite Instability High (MSI-H) or Proficient Mismatch Repair (pMMR) chemorefractory colorectal cancer (CRC) with liver metastasis.
• Participants must have histologically or cytologically confirmed adenocarcinoma of colorectal origin.
• MSS or pMMR status confirmed by IHC or PCR.
• Must have at least 1 measurable (≥ 1 cm) previously unirradiated hepatic lesion amenable to ablative RT and meeting dose constraints. A maximum of 5 hepatic lesions are allowed provided all are amenable to ablative RT and meet dose constraints. Must have at least 1 other unirradiated measurable (≥ 1cm) extrahepatic lesion, outside of RT field. Patients should ideally have a second unirradiated lesion, outside of RT field, that would be amenable for paired biopsies.
• Must have received or confirmed intolerance to 5-FU, Oxaliplatin, and Irinotecan (in any combination).
• Age ≥18 years
• ECOG performance status ≤ 1
• Life expectancy of greater than 3 months.
• Participants must meet the following organ and marrow function as defined below:
‣ Absolute Neutrophil Count (ANC) ≥ 1500 /mcL
⁃ White Blood Cells (WBC) ≥ 2000 /mcL
⁃ Platelets (PLT) ≥ 100,000 /mcL
⁃ Hemoglobin (HGB) ≥ 8 g/dL without transfusion within 2 weeks of measurement
⁃ AST and ALT ≤ 2.5 x ULN
⁃ Total Bilirubin ≤ 1.5 x ULN OR \< 3 mg/dL for participants with Gilbert Syndrome
⁃ Creatinine Clearance ≥ 40 mL/min if calculated using Cockcroft-Gault formula
• The effects of radiation on the developing human fetus are known to be teratogenic and the safety of Botensilimab and Balstilimab in pregnant women and their fetuses has not been established.
⁃ -Woman of childbearing potential (WOCBP) and men with WOCBP partners must agree to use highly effective contraceptive measures starting at screening through 5 months (180 days) after the last dose of balstilimab and/or botensilimab.
• WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG).
• Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• Ability to understand and the willingness to sign a written informed consent document.