This phase II trial tests the effect of the botensilimab in combination with balstilimab in treating patients with stage II/III colorectal adenocarcinoma with detectable circulating tumor (ct) deoxyribonucleic acid (DNA) in the blood. Immunotherapy with monoclonal antibodies, such as botensilimab and balstilimab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Giving botensilimab and balstilimab may be an effective combination to remove any remaining microscopic cancer cells in the bloodstream in patients with stage II/III colorectal adenocarcinoma. In addition, clearing the ctDNA from the blood may serve as an early indicator of treatment response.
Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of botensilimab (AGEN1181) in combination with balstilimab (AGEN2034) in patients < 18 years of age, children are excluded from this study
Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 (or Karnofsky ≥ 60%)
Absolute neutrophil count ≥ 1,000/mcL
Platelets ≥ 100,000/mcL
Patients who are receiving any other investigational agents
History of allergic reactions attributed to compounds of similar chemical or biologic composition to botensilimab (AGEN1181) and balstilimab (AGEN2034)
Patients that are pregnant, breast feeding, or planning to become pregnant while enrolled in the study, up to the end of treatment (EOT) visit, are excluded from this study because botensilimab (AGEN1181) and balstilimab (AGEN2034) are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with botensilimab (AGEN1181) and balstilimab (AGEN2034), breastfeeding should be discontinued if the mother is treated with botensilimab (AGEN1181) and balstilimab (AGEN2034)
Patients with microsatellite instability (MSI-high) or deficient mismatch repair (dMMR) CRC (MMR/MSI testing is required prior to enrollment)
Single group
Balstilimab
Biological/VaccineGiven IV
Biopsy Procedure
Procedure/SurgeryUndergo tumor tissue biopsy
Biospecimen Collection
Procedure/SurgeryUndergo urine and blood sample collection
Botensilimab
Biological/VaccineGiven IV
Radiographic Examination
Procedure/SurgeryUndergo imaging
Circulating tumor deoxyribonucleic acid (ctDNA) clearance
Will be defined as clearance of ctDNA and no radiographic evidence of disease. Will estimate clearance rate and its 95% confidence interval.
ctDNA clearance rate
Will evaluate the proportion of all included patients whose ctDNA converts from positive to negative. The proportion is presented together with 90% exact intervals.
Recurrence-free survival (RFS)
Median RFS and 95% confidence intervals will be estimated using the Kaplan-Meier method.
Overall survival (OS)
Will use Kaplan-Meier methods to evaluate time to event endpoints and will report median OS and its 95% confidence interval.
Incidence and severity of adverse events (AEs)
Severity of AEs will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. toxicity grading scale. Safety will be assessed by descriptive statistics and summarized in tabular format.
Time to ctDNA negative status
Summary statistics for biomarkers and their corresponding changes (or percent changes) from baseline will be tabulated by planned study. The time-course of biomarker measures will be investigated graphically. If an indication of meaningful pattern over time under treatment of botensilimab (AGEN1181) and balstilimab (AGEN2034) is observed, further analyses (e.g., by linear mixed model) may be performed to characterize the relationship.
Duration of ctDNA negative status
Summary statistics for biomarkers and their corresponding changes (or percent changes) from baseline will be tabulated by planned study. The time-course of biomarker measures will be investigated graphically. If an indication of meaningful pattern over time under treatment of botensilimab (AGEN1181) and balstilimab (AGEN2034) is observed, further analyses (e.g., by linear mixed model) may be performed to characterize the relationship.
Overall ctDNA negative rate
Summary statistics for biomarkers and their corresponding changes (or percent changes) from baseline will be tabulated by planned study. The time-course of biomarker measures will be investigated graphically. If an indication of meaningful pattern over time under treatment of botensilimab (AGEN1181) and balstilimab (AGEN2034) is observed, further analyses (e.g., by linear mixed model) may be performed to characterize the relationship.
Lead time from ctDNA detection to radiographic detection
Summary statistics for biomarkers and their corresponding changes (or percent changes) from baseline will be tabulated by planned study. The time-course of biomarker measures will be investigated graphically. If an indication of meaningful pattern over time under treatment of botensilimab (AGEN1181) and balstilimab (AGEN2034) is observed, further analyses (e.g., by linear mixed model) may be performed to characterize the relationship.
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