A Study of Botensilimab and Balstilimab for Colorectal Cancer With ctDNA+ After Surgery and Chemotherapy

Exclusion Criteria

• •Presence of metastatic or recurrent disease.
• •Known DNA polymerase epsilon (POLE) or DNA polymerase delta (POLD) activating mutation.
• •R1 (microscopic residual tumor) or R2 resection (macroscopic residual tumor at resection margin).
• •Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• •Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• •1. Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., dexamethasone containing antiemetic regimen or steroids as CT scan contrast premedication) may be enrolled.
• •2. The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed.
• •Hypersensitivity to botensilimab or balstilimab or any of its excipients.
• •Chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent
• •a. Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• •History of, or any evidence of active, non-infectious pneumonitis.
• •Active infection requiring systemic therapy.
• •Current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• •Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• •Pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 90 days after the last dose of trial treatment.
• •Prior therapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 agent.
• •Active autoimmune disease or history of autoimmune disease that required systemic treatment within 2 years of the start of study treatment (i.e., with use of disease-modifying agents or immunosuppressive drugs). The following are exceptions:
• •1. Subjects with vitiligo or alopecia
• •2. Subjects with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement or psoriasis not requiring systemic treatment
• •Known active TB (Bacillus tuberculosis).
• •Uncontrolled infection with human immunodeficiency virus (HIV). Patients on stable highly active antiretroviral therapy with undetectable viral load and normal CD4 counts for at least 6 months prior to study entry are eligible. Serological testing for HIV at screening is not required
• •Known to be positive for hepatitis B virus (HBV) surface antigen, or any other positive test for HBV indicating acute or chronic infection. Patients who are receiving or who have received anti-HBV therapy and have undetectable HBV DNA prior to study entry are eligible. Serological testing for HBV at screening is not required.
• •Known active hepatitis C virus (HCV) as determined by positive serology and confirmed by polymerase chain reaction (PCR). Patients on or who have received antiretroviral therapy are eligible provided they are virus-free by PCR for at least 6 months prior to study entry. Serological testing for HCV at screening is not required.
• •Received a live vaccine within 30 days of planned start of study therapy