Botensilimab and Balstilimab Optimization in Colorectal Cancer (BBOpCo)
This is a single-arm, interventional, pilot clinical trial. Fifteen evaluable patients will have tumor-informed ctDNA testing at baseline and start botensilimab and balstilimab treatment. They will receive botensilimab and balstilimab in 6-week cycles until progression, after which mFOLFOX6 and bevacizumab or panitumumab will be added to the regimen. Subjects will have safety testing at baseline and every two weeks while on study drug. Study treatment with botensilimab and balstilimab, mFOLFOX6, and bevacizumab or panitumumab will be continued until radiographic or clinical progression, toxicity, or patient withdrawal. Subjects will have one safety follow up visit 30 days after the last treatment and will be followed for survival every 12 weeks for up to 2 years.
• Male or female participants who are at least 18 years of age on the day of signing informed consent.
• Histologically confirmed metastatic and/or unresectable colorectal cancer without liver metastasis or known or suspected bone or brain metastases.
• a. Up to 3 patients with peritoneal carcinomatosis will be included. Other than those three, subjects must only have lung, lymph node, and locoregional sites of disease (primary tumor or serosal implant without carcinomatosis).
• Microsatellite stable disease.
• Subject must be willing to provide fresh biopsy of tumor lesion. Those who do not have a tumor lesion that is safe and amenable to biopsy may still be enrolled.
• ECOG performance status of 0 or 1.
• No prior systemic therapy for colon cancer.
• a. Subjects who received systemic therapy in the neoadjuvant or adjuvant setting may be eligible with approval from the principal investigator.
• Measurable disease per RECIST v1.1.
• Female participants must not be pregnant or breastfeeding and meet at least one of the following conditions:
∙ Not a woman of childbearing potential (WOCBP).
‣ A WOCBP must agree to use a reliable method of contraception during the treatment period and for at least 180 days after the last dose of study treatment.
• Male participants must practice effective contraceptive methods during the treatment period, unless documentation of infertility exists.
⁃ Expected to survive \>3 months per investigator assessment.
⁃ The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
⁃ Adequate organ function as defined below. Specimens must have been collected within 7 days prior to the start of study treatment:
∙ Absolute neutrophil count (ANC) ≥1500/µL
‣ Platelets ≥100,000/µL
‣ Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L (without packed red blood cell transfusion within the last 2 weeks)
‣ Creatinine OR measured or calculated creatinine clearance (GFR can be used in place of CrCl) ≤1.5 x ULN OR ≥45 mL/min for participant with creatinine levels \>1.5 x institutional ULN (Creatinine clearance should be calculated per institutional standard.)
‣ Total bilirubin ≤1.5 x ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \> 1.5 x ULN
‣ AST (SGOT) and ALT (SGPT) ≤2.5 x ULN
‣ International normalized ratio (INR) OR prothrombin time (PT) ≤1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
‣ Activated partial thromboplastin time (aPTT) ≤1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants