Testing the Combination of Anti-Cancer Drugs, Botensilimab (AGEN1181) and Balstilimab (AGEN2034), After Standard Treatment for Colorectal Cancer, Combat Trial

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

Total bilirubin ≤ 1.5 x the institutional upper limit of normal (ULN)

* Patients with documented Gilbert's syndrome may be included if total bilirubin is ≤ 3 x ULN

Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 x institutional ULN

Creatinine clearance ≥ 40 mL/min

* Creatinine clearance (Clcr) can either be measured in a 24-hour urine collection or estimated by the Cockcroft-Gault equation

Histological confirmation of colorectal cancer (adenocarcinoma) (CRC)

Post-R0 resection of stages II and III CRC and all planned adjuvant therapies have been completed. Patients with rectal cancer who have completed total neoadjuvant therapy and have complete clinical response (cCR) and are on wait-and-watch approach will be permitted as long as they have no radiographic and endoscopic evidence of disease recurrence at the time of enrollment

No evidence of radiographic disease within 28 days (before or after) of a positive ctDNA assay

Evident MRD as defined by positive ctDNA (Signatera™ MRD) assay. MRD status will be confirmed with the Signatera™ assay prior to initiation of study therapy. MRD positivity is defined based on testing performed after completion of planned standard treatment (e.g., surgery or chemotherapy), provided assessments occur at least 3 weeks post-surgery (if no adjuvant therapy is planned) and at least 3 weeks after last chemotherapy (if adjuvant therapy is given) to avoid transient false positives. The window from MRD positivity to first dose should be no more than 90 days

Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated

Patients 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

The effects of botensilimab (AGEN1181) and balstilimab (AGEN2034) on the developing human fetus are unknown. Women of child-bearing potential \[refer to MD Anderson (MDA) Policy CLN 1114\] must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for at least 4 months after the last dose. This includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following:

* Postmenopausal (no menses in greater than or equal to 12 consecutive months)

* History of hysterectomy or bilateral salpingo-oophorectomy

* Ovarian failure (follicle stimulating hormone and estradiol in menopausal range, who have received whole pelvic radiation therapy)

* History of bilateral tubal ligation or another surgical sterilization procedure.)

* Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), intrauterine device (IUD), tubal ligation or hysterectomy, subject/partner post vasectomy, implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately

* Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of administration. In addition, women of childbearing age should not donate egg(s) and men should not donate sperm for the duration of study participation and 6 months after completion of the last dose of botensilimab (AGEN1181) and balstilimab (AGEN2034).

Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants

What this study is about