Botensilimab Plus Balstilimab and Fasting Mimicking Diet Plus Vitamin C for Patients With KRAS-Mutant Metastatic Colorectal Cancer

NCT06336902 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 3C-23-11NCI-2024-01368P30CA014089
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 3

Brief Summary

This phase Ib trial tests the safety, side effects, and effectiveness of botensilimab, and balstilimab in combination with a fasting mimicking diet and high dose vitamin C in treating patients with KRAS-mutant metastatic colorectal cancer. Botensilimab and balstilimab are monoclonal antibodies that may interfere with the ability of tumor cells to grow and spread. KRAS is protein found on some tumor cells that is involved in the growth of tumor cells. KRAS mutant cells have been found to be more sensitive to vitamin C induced growth suppression in the presence of low-sugar (glucose). A fasting mimicking diet, a plant-based, calorie reduced, low-sugar diet alternating with refeeding periods, may positively change the way the body responds to cancer treatment. Vitamin C is a nutrient that the body needs in small amounts to function and stay healthy. It is an antioxidant that that can help prevent cell damage and may block growth and spread of tumor cells. Botensilimab and balstilimab in combination with a fasting mimicking diet and high dose vitamin C may be safe, tolerable and effective in treating patients with KRAS-mutant metastatic colorectal cancer.

Conditions

Metastatic Colorectal Adenocarcinoma; Stage IV Colorectal Cancer AJCC v8

Outcome Measures

Primary Outcomes (2)

• Proportion of patients who adhere to the fast mimicking diet

  Adherence will be defined as the percentage of patients who adhere to the fasting-mimicking diet ≥ 75% of the designated days and receive all doses of study drugs for at least any 2 cycles of therapy during the course of the study. Adherence will be reported overall and by cycle started.

  Up to 30 months

• Incidence of adverse events (AEs)

  The frequency and severity of treatment-related events will be assessed using Common Terminology Criteria for Adverse Events version 5.0. Descriptive statistics will be used to summarize AEs including counts for categorical measures and means for continuous measures. Incidence of AEs will be reported overall and by cycle started.

  Up to 30 months

Secondary Outcomes (3)

• Overall response rate (ORR)

  Up to 30 months

• Progression-free survival (PFS)

  Up to 30 months

• Overall survival (OS)

  Up to 30 months

Study Arms (1)

Treatment (botensilimab, balstilimab, FMD, vitamin C)

EXPERIMENTAL

Patients receive botensilimab IV over 30 minutes on day 1 of each cycle for up to 4 cycles. Patients receive balstilimab IV over 30 minutes and vitamin C IV over 30 minutes on days 1, 15 and 29 of each cycle. Patients undergo a FMD on days -4 to -1 of each cycle. Cycles repeat every 42 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT scans and MRI throughout the study.

Biological: Balstilimab; Procedure: Biospecimen Collection; Biological: Botensilimab; Procedure: Computed Tomography; Other: Dietary Intervention; Procedure: Magnetic Resonance Imaging; Dietary Supplement: Vitamin C

Interventions

Balstilimab BIOLOGICAL

Given IV

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

Treatment (botensilimab, balstilimab, FMD, vitamin C)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

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

Treatment (botensilimab, balstilimab, FMD, vitamin C)

Botensilimab BIOLOGICAL

Given IV

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

Treatment (botensilimab, balstilimab, FMD, vitamin C)

Computed Tomography PROCEDURE

Undergo CT scan

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 (botensilimab, balstilimab, FMD, vitamin C)

Dietary Intervention OTHER

Undergo FMD

Also known as: Dietary Modification, intervention, dietary, Nutrition Intervention, Nutrition Interventions, Nutritional Interventions

Treatment (botensilimab, balstilimab, FMD, vitamin C)

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 (botensilimab, balstilimab, FMD, vitamin C)

Vitamin C DIETARY_SUPPLEMENT

Given IV

Treatment (botensilimab, balstilimab, FMD, vitamin C)

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed microsatellite stable (MSS) metastatic colorectal adenocarcinoma with any KRAS mutation (as determined by a Clinical Laboratory Improvement Act \[CLIA\]-certified lab), including metastases to liver, lung, etc.
• Disease progression, intolerance or contraindication to a fluoropyrimidine, oxaliplatin, irinotecan
• ≥ 18 years of age
• Performance status Eastern Cooperative Oncology Group (ECOG) 0-1
• Estimated life expectancy ≥ 3 months
• Body mass index (BMI) ≥ 18.5
• Absolute neutrophil count ≥ 1,500/mcL
• Hemoglobin ≥ 8.0 g/dL
• Platelets ≥ 75,000/mcL
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (for patients with Gilbert syndrome ≤ 3.0 x ULN)
• Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 3 x ULN
• Creatinine ≤ 1.5 x ULN
• Measurable disease as defined by RECIST 1.1
• No history of prior or current malignancy that requires active treatment
• Female patients of childbearing potential must be willing to use highly effective contraceptive measures starting with the Screening visit through 90 days after last dose of study treatment.

You may not qualify if:

• Patients with a current diagnosis of diabetes mellitus are not eligible for this study.
• Note: Patients with pre-diabetes or previous diabetes or glucose intolerance and who are currently not taking any diabetes medications are eligible
• Patients taking medications that cannot be safely stopped during the fasting periods or which may not be safely taken without food are not eligible for this study
• Received prior systemic cytotoxic chemotherapy, biological therapy, radiotherapy, or major surgery within 3 weeks prior to first dose of study drug. A 1-week washout is permitted for palliative radiation to non-central nervous system (CNS) disease, with approval from the principal investigator
• History of syncope with caloric restriction or another medical comorbidity which would make fasting potentially dangerous
• Current use of oral vitamin C supplements
• Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 3 weeks of first dose of current study drug
• Expected to require any other form of systemic or localized antineoplastic therapy while on trial (including maintenance therapy with another agent, radiation therapy, and/or surgical resection)
• History of anti-PD1 or anti-CTLA4 therapy
• Unresolved toxicity ≥ CTCAE grade 2 except for neuropathy, alopecia
• Untreated brain or leptomeningeal metastases or previously treated CNS metastases with any of the following: residual neurologic deficit; history of seizures; ongoing requirement of steroids, exceeding prednisone 10 mg daily dose
• Patients who have uncontrolled or severe hyponatremia, hypernatremia, syndrome of inappropriate antidiuretic hormone secretion (SIADH), hypokalemia, hyperkalemia, hypomagnesemia, or hypermagnesemia
• Patients who have glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis, or other conditions predisposing patient to hemolysis
• Patients who have a history of oxalate renal calculi
• Major surgery within 4 weeks of first dose of immunotherapy

Sponsors & Collaborators

• University of Southern California: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Saint Jude Medical Center / Providence Medical Foundation

Fullerton, California, 92835, United States

RECRUITING

Los Angeles General Medical Center

Los Angeles, California, 90033, United States

RECRUITING

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

balstilimab; Specimen Handling; Diet Therapy; Magnetic Resonance Spectroscopy; Ascorbic Acid

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Nutrition Therapy; Therapeutics; Spectrum Analysis; Chemistry Techniques, Analytical; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates

Study Officials

• Diana Hanna, MD

  University of Southern California

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Charlean Ketchens, RN

CONTACT

323-865-0451; Charlean.Ketchens@med.usc.edu

Rabia Rehman

CONTACT

323-865-0451; Rabia.Rehman@med.usc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2024
• First Posted: March 29, 2024
• Study Start: January 15, 2025
• Primary Completion (Estimated): January 15, 2027
• Study Completion (Estimated): January 15, 2028
• Last Updated: March 17, 2026

Record last verified: 2025-12

Locations

US (3)