FOLFOX, Botensilimab, and Balstilimab for the Treatment of Localized Rectal Cancer Before Surgery

NCT06780787 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 24589NCI-2025-00072P30CA033572
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Rectal Adenocarcinoma; Stage IIA Rectal Cancer AJCC v8; Stage III Rectal Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• 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

  At 3 months after treatment

Secondary Outcomes (7)

• Overall response rate (ORR)

  Up to 5 years

• Incidence of adverse events (AE) and serious adverse events (SAE)

  Up to 90 days post-treatment

• Disease free survival (DFS)

  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)

  From the date of study enrollment until objective tumor progression or death, assessed up to 5 years

• Pelvic recurrence rate

  At 3 years after treatment

Study Arms (1)

Treatment (FOLFOX, botensilimab, balstilimab)

EXPERIMENTAL

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

Interventions

Balstilimab BIOLOGICAL

Given IV

Also known as: AGEN 2034, AGEN-2034, AGEN2034

Treatment (FOLFOX, botensilimab, balstilimab)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (FOLFOX, botensilimab, balstilimab)

Botensilimab BIOLOGICAL

Given IV

Also known as: AGEN 1181, AGEN-1181, AGEN1181, Anti-CTLA-4 Monoclonal Antibody AGEN1181

Treatment (FOLFOX, botensilimab, balstilimab)

Capecitabine DRUG

Given PO

Also known as: Ro 09-1978/000, Xeloda

Treatment (FOLFOX, botensilimab, balstilimab)

Computed Tomography PROCEDURE

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

Treatment (FOLFOX, botensilimab, balstilimab)

Digital Rectal Examination PROCEDURE

Undergo digital rectal exam

Also known as: DRE

Treatment (FOLFOX, botensilimab, balstilimab)

Endoscopic Biopsy PROCEDURE

Undergo biopsy with endoscopic exam

Also known as: Endoscopy and Biopsy

Treatment (FOLFOX, botensilimab, balstilimab)

Fluorouracil DRUG

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

Treatment (FOLFOX, botensilimab, balstilimab)

Leucovorin Calcium DRUG

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

Treatment (FOLFOX, botensilimab, balstilimab)

Magnetic Resonance Imaging PROCEDURE

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

Treatment (FOLFOX, botensilimab, balstilimab)

Oxaliplatin DRUG

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

Treatment (FOLFOX, botensilimab, balstilimab)

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Treatment (FOLFOX, botensilimab, balstilimab)

Sigmoidoscopy PROCEDURE

Undergo sigmoidoscopy

Also known as: Proctosigmoidoscopy

Treatment (FOLFOX, botensilimab, balstilimab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• Assent, when appropriate, will be obtained per institutional guidelines
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies
• If unavailable, exceptions may be granted with study principal investigator (PI) approval
• Age: ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) ≤ 1
• Histologically confirmed adenocarcinoma of the rectum
• Rectal involvement defined as involvement of the rectum within 12 cm proximal from anal verge
• Radial margin of at least 3mm from the mesorectal fascia, with no threatened circumferential tumor margin based on MRI. No more than 4 lymph nodes (LN) with short axis \> 1 cm
• T3N0, or TxN1 or TxN2 clinical stage based on MRI staging
• No evidence of distant metastatic disease based on imaging studies including CT chest and CT or MRI of abdomen and pelvis
• Absolute neutrophil count (ANC) ≥ 1,500/mm\^3
• Without bone marrow involvement: Platelets ≥ 100,000/mm\^3
• Hemoglobin ≥ 9g/dL
• NOTE: Red blood cell transfusions are not permitted within 14 days of hemoglobin assessment

You may not qualify if:

• Any treatment for rectal cancer prior to enrollment that includes (but not limited to) chemotherapy, radiation, and/or biological therapy
• Any prior immunotherapy
• 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
• Surgical intervention within 4 weeks prior to study treatment, except for minor procedures such as port placement or biopsies
• Concurrent malignancy other than the diagnosis of rectal cancer, with the exception of curatively resected non-melanoma skin cancer, cervical cancer in situ, prostate cancer Gleason 6 or below that is localized to the prostate, or any other curatively resected cancer from which the patient remains in remission for at least 2 years without treatment
• Unstable cardiac disease as defined by one of the following:
• Cardiac events such as myocardial infarction (MI) within the past 6 months
• NYHA (New York Heart Association) heart failure class III-IV
• Uncontrolled atrial fibrillation
• 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 of acute thrombotic venous events in the last 30 days before enrollment. If within 30 days, the patient should be on anticoagulants and without symptoms

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

balstilimab; Specimen Handling; Capecitabine; Endoscopic Mucosal Resection; Endoscopy; Biopsy; Fluorouracil; dehydroftorafur; Leucovorin; Magnetic Resonance Spectroscopy; Oxaliplatin; Radiotherapy; Radiation; Sigmoidoscopy

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Endoscopy, Gastrointestinal; Endoscopy, Digestive System; Diagnostic Techniques, Digestive System; Diagnostic Techniques, Surgical; Digestive System Surgical Procedures; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures; Cytodiagnosis; Cytological Techniques; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Spectrum Analysis; Chemistry Techniques, Analytical; Coordination Complexes; Organic Chemicals; Therapeutics; Physical Phenomena; Colonoscopy

Study Officials

• Marwan Fakih

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2025
• First Posted: January 17, 2025
• Study Start: May 20, 2025
• Primary Completion (Estimated): November 5, 2027
• Study Completion (Estimated): November 5, 2027
• Last Updated: June 26, 2025

Record last verified: 2025-06

Locations

US (1)