Neoadjuvant Botensilimab and Balstilimab for the Treatment of Advanced Resectable Colorectal Cancer NEST3

Recruiting now · Phase 2

Conditions studied: Advanced Colon Adenocarcinoma, Advanced Colorectal Adenocarcinoma, Advanced Rectal Adenocarcinoma, Stage IIB Colon Cancer AJCC v8, Stage IIB Rectal Cancer AJCC v8, Stage IIC Colon Cancer AJCC v8, Stage IIC Rectal Cancer AJCC v8, Stage IIIA Colon Cancer AJCC v8, Stage IIIA Rectal Cancer AJCC v8, Stage IIIB Colon Cancer AJCC v8, Stage IIIB Rectal Cancer AJCC v8, Stage IIIC Colon Cancer AJCC v8, Stage IIIC Rectal Cancer AJCC v8

In brief

This phase II trial tests how well giving botensilimab and balstilimab prior or to surgery (neoadjuvent) works for the treatment of colorectal cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and that can be removed by surgery (resectable) colorectal cancer. Immunotherapy with monoclonal antibodies, such as botensilimab and balstilimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving botensilimab and balstilimab before surgery may make the tumor smaller. Giving neoadjuvant botensilimab and balstilimab may be effective for the treatment of advanced resectable colorectal cancer.

Key facts

Study ID: NCT07595874
Run by: City of Hope Medical Center
People needed: 100
Starts: 2026-12-27
Expected to finish: 2027-05-27
Last updated by the study team: 2026-07-01

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Documented informed consent of the participant and Legally Authorized Representative (when applicable)
Assent, when appropriate, will be obtained and documented for adults lacking capacity per institutional guidelines
Agreement to allow the use of tissue from past and future surgery and standard of care biopsies
Age: ≥ 18 years
Eastern Cooperative Oncology Group (ECOG) ≤ 2
Histologically confirmed or cytologically confirmed colorectal adenocarcinoma. Patients with high grade dysplasia on histology plus unequivocal endoscopic or radiological evidence of invasive cancer are eligible.
Patients diagnosed with rectal cancer who will be treated like colon cancer with curative-intent surgery first and no radiation are also eligible, including:
Upper rectum or rectosigmoid considered as non-rectal and not undergoing neoadjuvant treatment
The tumor component should not extend to less 12 cm from the anal verge.
Any patient with rectal cancer for whom radiotherapy is not advised is included in this protocol (i.e., excluding rectal adenocarcinomas warranting treatment with chemoradiation)
Microsatellite stability by mismatch repair by immunohistochemistry, polymerase chain reaction and/or other Clinical Laboratory Improvement Amendments (CLIA) certified next generation sequencing. Only patients with mismatch repair proficient or microsatellite stable (pMMR/MSS) tumors are allowed to enroll in the study
Candidate for and planning a curative resection. Must have surgeon identified
T4, N+ (American Joint Committee on Cancer [AJCC] TNM staging criteria), or both by central radiographic assessment.
Note: Patients with T3N0 stage IIA are excluded. Stage IIB, IIC, IIIA, IIIB, and IIIC are included. Patients with stage IV disease are excluded
Absolute neutrophil count (ANC) ≥ 1,500/mm\^3
Platelets ≥ 75,000/mm\^3
NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment
Hemoglobin ≥ 8 g/dL
NOTE: Red blood cell transfusions are permitted. Patients should not have active clinically significant bleeding requiring regular transfusions. Iron infusions are also allowed
Total bilirubin ≤ 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease, in which case the liver function tests must meet the other eligibility in the protocol)
Aspartate aminotransferase (AST) ≤ 3.0 x ULN
Alanine aminotransferase (ALT) ≤ 3.0 x ULN
Creatinine clearance of ≥ 40 mL/min per the Cockcroft-Gault formula
Women of childbearing potential (WOCBP): negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
Agreement by females and males of childbearing potential* to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 9 months for women, and at least 6 months for men, after the last dose of oxaliplatin therapy. If patients discontinue oxaliplatin more than 9 months (females) or 6 months (males) before discontinuation of balstilimab and/or botensilimab, females and males of childbearing potential must use an effective method of birth control or abstain from sexual activity for the course of the study through at least 120 days after the last dose of balstilimab and/or botensilimab.

You may not qualify if…

Any treatment for colorectal cancer prior to enrollment that includes (but not limited to) chemotherapy, surgery, radiation, immunotherapy and/or biological therapy.
Note: Surgical intervention e.g. a diverting ostomy to relieve an obstruction from colorectal cancer, those patients will be allowed to enter the study as long as no distant metastatic disease
Patients with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) within 14 days or another immunosuppressive medication within 30 days of the first dose of study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease
Prior allogeneic organ transplantation
Herbal medications that require a prescription or are anti-cancer
Other active malignancy. 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. Please note: patients with more than 1 colorectal cancer tumor at diagnosis (as long as no stage IV disease) are allowed to participate. Pathologic response to each of the tumors will be examined
Active acute colonic obstruction. Patients whose obstruction is relieved by a successful defunctioning stoma are allowed once recovered to a fitness level consistent with the other eligibility criteria
Clinically significant uncontrolled illness
Females only: Pregnant or breastfeeding
Prior allergic reaction or hypersensitivity to any of the study drug components
Active autoimmune disease or history of autoimmune disease that required systemic treatment within 2 years before starting treatment, i.e., with use of disease-modifying agents or immunosuppressive drugs (excluding hypothyroidism, vitiligo, and psoriasis that is controlled with topical management)
History or current evidence of any condition, co-morbidity, therapy, that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator
Uncontrolled infection with human Immunodeficiency virus (HIV). Patients on stable highly active antiretroviral therapy (HAART) are eligible. Serological testing for HIV at screening is not required
Uncontrolled infection with hepatitis B virus. Patients who are receiving or who have received anti-HBV therapy 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. Serological testing for HCV at screening is not required
Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Where it is running

CTCA at Western Regional Medical Center — Goodyear, Arizona, United States (enrolling)
City of Hope Corona — Corona, California, United States (enrolling)
City of Hope Medical Center — Duarte, California, United States (enrolling)
City of Hope Seacliff — Huntington Beach, California, United States (enrolling)
City of Hope at Irvine Lennar — Irvine, California, United States (enrolling)
City of Hope at Long Beach Elm — Long Beach, California, United States (enrolling)
City of Hope South Pasadena — South Pasadena, California, United States (enrolling)
City of Hope Upland — Upland, California, United States (enrolling)
City of Hope Atlanta Cancer Center — Newnan, Georgia, United States (enrolling)
City of Hope at Illinois Chicago Downtown — Chicago, Illinois, United States (enrolling)
City of Hope at Chicago — Zion, Illinois, United States (enrolling)

Full record on ClinicalTrials.gov

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