A Phase 2 interventional study of Balstilimab and Biospecimen Collection in Rectal Adenocarcinoma, Stage IIA Rectal Cancer AJCC v8 and Stage III Rectal Cancer AJCC v8, sponsored by City of Hope Medical Center. Recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-06-29.
Sponsored by City of Hope Medical Center · Phase 2, Interventional, and Treatment
This phase II trial tests how well fluorouracil, oxaliplatin and leucovorin calcium (folinic acid) (FOLFOX) with botensilimab and balstilimab given before surgery (neoadjuvant) works in treating patients with rectal adenocarcinoma that has not spread to other parts of the body (localized). Currently, neoadjuvant therapy for rectal cancer includes chemotherapy and chemoradiation. Despite these aggressive treatments, only about half of patients achieve a complete clinical response. In fact, over half of rectal cancer patients go on to have surgery and often suffer post-surgery complications involving urine and bowel problems. Thus, there has been an increased focus on non-surgical treatments. Chemotherapy drugs, such as fluorouracil, oxaliplatin and leucovorin calcium, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. 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 neoadjuvant FOLFOX with botensilimab and balstilimab may improve the rate of complete response and decrease the need for surgery and radiation therapy in patients with localized rectal adenocarcinoma.
PRIMARY OBJECTIVE:
I. To determine the complete clinical response rate for patients with localized rectal cancer treated with neoadjuvant FOLFOX + botensilimab + balstilimab (FOLFOX-BB).
SECONDARY OBJECTIVES:
I. To evaluate the safety of FOLFOX-BB in patients with localized rectal cancer treated with neoadjuvant FOLFOX + botensilimab + balstilimab (FOLFOX-BB).
II. To estimate 3 year disease free survival rates in patients treated with FOLFOX-BB.
III. To estimate 3 year pelvic recurrence rates in patients with localized rectal cancer treated with neoadjuvant FOLFOX + botensilimab + balstilimab (FOLFOX-BB).
IV. To estimate the duration of response in patients with localized rectal cancer treated with neoadjuvant FOLFOX + botensilimab + balstilimab (FOLFOX-BB).
V. To evaluate 5 year survival rates in patients in patients with localized rectal cancer treated with neoadjuvant FOLFOX + botensilimab + balstilimab (FOLFOX-BB).
EXPLORATORY OBJECTIVES:
I. To examine changes in tumor microenvironment in response to FOLFOX-BB. II. To assess serial blood biomarkers to identify potential correlations with treatment response and outcomes.
OUTLINE:
Patients receive leucovorin calcium intravenously (IV) over 2 hours, oxaliplatin IV over 2 hours, and fluorouracil IV over 46 hours on day 1 of each cycle. Patients also receive botensilimab IV over 60 minutes on day 1 of cycles 1 and 4 and balstilimab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 14 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients with complete clinical response may continue to receive balstilimab alone for an additional 12 cycles. Patients without complete clinical response may receive radiation therapy once daily (QD) on weekdays and capecitabine orally (PO) twice daily (BID) concurrently on days of radiation therapy per standard of care. Additionally, patients undergo blood sample collection, biopsy with endoscopy examination (exam), sigmoidoscopy, digital rectal exam, computed tomography (CT) and magnetic resonance imaging (MRI) throughout the study.
After completion of study treatment, patient are followed at 30 and 90 days, then every 3 months within 1 year of start of treatment, followed by every 6 months for up to 2 years.
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Documented informed consent of the participant and/or legally authorized representative
Agreement to allow the use of archival tissue from diagnostic tumor biopsies
Hemoglobin ≥ 9g/dL
Women of childbearing potential (WOCBP): Negative urine or serum pregnancy test
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
Exclusion Criteria:
Unstable cardiac disease as defined by one of the following:
Patients receive leucovorin calcium IV over 2 hours, oxaliplatin IV over 2 hours, and fluorouracil IV over 46 hours on day 1 of each cycle. Patients also receive botensilimab IV over 60 minutes on day 1 of cycles 1 and 4 and balstilimab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 14 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients with complete clinical response may continue to receive balstilimab alone for an additional 12 cycles. Patients without complete clinical response may receive radiation therapy QD on weekdays and capecitabine PO BID concurrently on days of radiation therapy per standard of care. Additionally, patients undergo blood sample collection, biopsy with endoscopy exam, sigmoidoscopy, digital rectal exam, CT and MRI throughout the study.
Biological: Balstilimab · Procedure: Biospecimen Collection · Biological: Botensilimab · Drug: Capecitabine · Procedure: Computed Tomography · Procedure: Digital Rectal Examination · Procedure: Endoscopic Biopsy · Drug: Fluorouracil · Drug: Leucovorin Calcium · Procedure: Magnetic Resonance Imaging · Drug: Oxaliplatin · Radiation: Radiation Therapy · Procedure: Sigmoidoscopy
Given IV
Also known as: AGEN 2034, AGEN-2034, AGEN2034
Undergo blood sample collection
Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection
Given IV
Also known as: AGEN 1181, AGEN-1181, AGEN1181, Anti-CTLA-4 Monoclonal Antibody AGEN1181
Given PO
Also known as: Ro 09-1978/000, Xeloda
Undergo CT
Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography
Undergo digital rectal exam
Also known as: DRE
Undergo biopsy with endoscopic exam
Also known as: Endoscopy and Biopsy
Given IV
Also known as: 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-Fu, 5FU, AccuSite, Carac, Fluoro Uracil, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Ribofluor, Ro 2-9757, Ro-2-9757
Given IV
Also known as: Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate, Calcium Leucovorin, Calfolex, Calinat, Cehafolin, Citofolin, Citrec, Citrovorum Factor, Cromatonbic Folinico, Dalisol, Disintox, Divical, Ecofol, Emovis, Factor, Citrovorum, Flynoken A, Folaren, Folaxin, FOLI-cell, Foliben, Folidan, Folidar, Folinac, Folinate Calcium, folinic acid, Folinic Acid Calcium Salt Pentahydrate, Folinoral, Folinvit, Foliplus, Folix, Imo, Lederfolat, Lederfolin, Leucosar, leucovorin, Rescufolin, Rescuvolin, Tonofolin, Wellcovorin
Undergo MRI
Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI
Given IV
Also known as: 1-OHP, Ai Heng, Aiheng, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, Elplat, JM 83, JM-83, JM83, Oxalatoplatin, Oxalatoplatinum, RP 54780, RP-54780, RP54780, SR 96669, SR-96669, SR96669
Undergo radiation therapy
Also known as: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation
Undergo sigmoidoscopy
Also known as: Proctosigmoidoscopy
Complete clinical response (cCR) rate
Data will be summarized using descriptive statistics for continuous variables and frequencies and percentages will be used for categorical variables. Univariate logistic regression was used to estimate odds ratios (OR) and 90% confidence interval (CI) for cCR
Time frame: At 3 months after treatment
Overall response rate (ORR)
ORR is calculated as the number of patients with complete response (per Response Evaluation Criteria in Solid Tumors version \[v\] 1.1) divided by the total number of treated/evaluable subjects. Data will be summarized using descriptive statistics for continuous variables and frequencies and percentages will be used for categorical variables. Univariate logistic regression was used to estimate OR and 90% CI. Cox proportional hazards models were used to estimate hazard ratios (HR) with 95% CI.
Time frame: Up to 5 years
Incidence of adverse events (AE) and serious adverse events (SAE)
AE and SAE will be described and graded at all dose levels using Common Terminology Criteria in Adverse Events v 5.0. Data will be summarized using descriptive statistics for continuous variables and frequencies and percentages will be used for categorical variables.
Time frame: Up to 90 days post-treatment
Disease free survival (DFS)
Data will be summarized using descriptive statistics for continuous variables and frequencies and percentages will be used for categorical variables. Univariate logistic regression was used to estimate OR and 90% CI. Cox proportional hazards models were used to estimate HR with 95% CI. DFS distributions will be estimated using the Kaplan-Meier method.
Time frame: From the date of study enrollment until the recurrence of disease or death, whichever occurs first, assessed at 3 years post-treatment
Progression-free survival (PFS)
Data will be summarized using descriptive statistics for continuous variables and frequencies and percentages will be used for categorical variables. PFS distributions will be estimated using the Kaplan-Meier method. Kaplan-Meier method was used to plot PFS curves, and the log-rank test was applied to compare the distribution between groups. Cox proportional hazards models were used to estimate HR with 95% CI.
Time frame: From the date of study enrollment until objective tumor progression or death, assessed up to 5 years
Pelvic recurrence rate
Data will be summarized using descriptive statistics for continuous variables and frequencies and percentages will be used for categorical variables.
Time frame: At 3 years after treatment
Duration of response (DOR)
Data will be summarized using descriptive statistics for continuous variables and frequencies and percentages will be used for categorical variables. DOR distributions will be estimated using the Kaplan-Meier method.
Time frame: From treatment response to progression or death, assessed up to 3 years
Overall survival (OS)
Data will be summarized using descriptive statistics for continuous variables and frequencies and percentages will be used for categorical variables. OS distributions will be estimated using the Kaplan-Meier method. Kaplan-Meier method was used to plot OS curves, and the log-rank test was applied to compare the distribution between groups. Cox proportional hazards models were used to estimate HR with 95% CI.
Time frame: From the date of study enrollment to the date of death, assessed up to 5 years post-treatment
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