FOLFOX and Bevacizumab in Combination With Botensilimab and Balstilimab (3B-FOLFOX) for the Treatment of Microsatellite Stable (MSS) Metastatic Colorectal Cancer
A Phase I/II Clinical Trial of FOLFOX Bevacizumab Plus Botensilimab and Balstilimab (3B-FOLFOX) in Patients With MSS Metastatic Colorectal Cancer
3 other identifiers
interventional
20
1 country
1
Brief Summary
This phase I/II trial tests the safety, side effects, best dose, and efficacy of FOLFOX and bevacizumab in combination with botensilimab and balstilimab (3B-FOLFOX) in treating patients with microsatellite stable (MSS) colorectal cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Chemotherapy drugs, such as FOLFOX, 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. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Balstilimab and botensilimab are in a class of medications called monoclonal antibodies. They bind to proteins, called PD-L1 and CTLA-4, which is found on some types of tumor cells. These PD-1 and CTLA-4 proteins are known to affect the body's defense mechanism to identify and fight against tumor cells. The combination of these drugs may lead to improved disease control and outcomes in patients with MSS metastatic colorectal cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started May 2023
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 17, 2022
CompletedFirst Posted
Study publicly available on registry
November 25, 2022
CompletedStudy Start
First participant enrolled
May 3, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 23, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 23, 2026
November 10, 2025
November 1, 2025
3.1 years
November 17, 2022
November 6, 2025
Conditions
Outcome Measures
Primary Outcomes (2)
Incidence of adverse events (phase I)
Toxicity, graded according to the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. A dose limiting toxicity is a toxicity that occurs in the first 6 weeks of treatment with 3B-FOLFOX and that is attributed at least as possibly related to the study drugs
Up to 6 weeks
Overall response (phase II)
As assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Will examine the proportion of the liver metastasis among the 60 enrolled patients and carry out subgroup analysis for overall response for patients with and without liver metastasis.
Up to 5 years
Secondary Outcomes (8)
Overall response (phase I)
Up to 5 years
Progression-free survival (PFS) (phase I)
Time to disease progression/ relapse or death as a result of any cause, assessed up to 5 years
Overall survival (OS) (phase I)
Time to death as a result of any cause, assessed up to 5 years
PFS (phase II)
Time to disease progression or death as a result of any cause, assessed up to 5 years
OS (phase II)
Time to death as a result of any cause, assessed up to 5 years
- +3 more secondary outcomes
Study Arms (3)
Phase I (3B-FOLFOX)
EXPERIMENTALPatients receive FOLFOX, bevacizumab, balstilimab, and botensilimab IV on study. Patients undergo an x-ray, CT scan, PET scan, and/or MRI throughout the trial. Patients also undergo blood sample collection during screening and on study.
Phase II, Arm I (3B-FOLFOX)
EXPERIMENTALPatients receive FOLFOX, bevacizumab and balstilimab IV with botensilimab IV at a lower dose on study. Patients undergo an x-ray, CT scan, PET scan, and/or MRI throughout the trial. Patients also undergo blood sample collection during screening and on study.
Phase II, Arm II (3B-FOLFOX)
EXPERIMENTALPatients receive FOLFOX, bevacizumab and balstilimab IV with botensilimab IV at a higher dose on study. Patients undergo an x-ray, CT scan, PET scan, and/or MRI throughout the trial. Patients also undergo blood sample collection during screening and on study.
Interventions
Given IV
Given IV
Undergo a blood sample collection
Given IV
Undergo a CT scan
Given IV
Given IV
Undergo MRI
Given IV
Undergo a PET scan
Undergo an x-ray
Eligibility Criteria
You may qualify if:
- Documented informed consent of the participant and/or legally authorized representative
- Assent, when appropriate, will be obtained per institutional guidelines
- Age: \>= 18 years
- Eastern Cooperative Oncology Group (ECOG) =\< 1
- Life expectancy \>= 3 months
- Patients should have a pathologically proven diagnosis of colorectal adenocarcinoma
- Histological or cytological confirmed microsatellite stable (MSS) adenocarcinoma of colon or rectum. Microsatellite status should be performed per local standard of practice (immunohistochemistry \[IHC\] and or polymerase chain reaction \[PCR\], or next-generation sequencing, the presence of POLE mutations will be collected if available through next-generation sequencing)
- Patients should have measurable metastatic disease as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines
- Patients should not have a history of perforations or fistulas
- For the safety cohorts (phase I): Metastatic colorectal cancer with 0 to 2 prior lines of therapy prior to enrollment on study and without prior progression within 3 months from last dose of oxaliplatin, in the event of prior oxaliplatin exposure. Evidence of radiographic progression after last treatment before enrollment should be documented
- Patients with prior FOLFOX therapy should not have required dose modifications and should not have experienced unacceptable toxicities
- Patients with other prior 5-FU-based therapies should not have required prior fluorouracil (5-FU) dose modifications below 2400 mg/m\^2 every 2 weeks
- No prior oxaliplatin hypersensitivity
- weeks should have elapsed from last prior chemotherapy and initiation of study treatment
- For the efficacy cohorts (phase II): No prior treatment for metastatic disease. If prior FOLFOX adjuvant therapy was administered, there should be no evidence of disease relapse within the first 12 months after completion of adjuvant therapy
- +16 more criteria
You may not qualify if:
- 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
- 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
- Uncontrolled hypertension, defined as systolic blood pressure (SBP) \>150, diastolic blood pressure (DBP) \> 90
- 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
- Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction within 12 months of enrollment, unstable angina, congestive heart failure (New York Heart Association class \>= III), or serious uncontrolled cardiac arrhythmia requiring medication
- Obstructive bowel symptoms related to unresected primary or carcinomatosis
- Any persistent toxicities (Common Terminology Criteria for Adverse Events \[CTCAE\] grade \>= 2) from prior cancer therapy, excluding endocrinopathies stable on medication, stable neuropathy that is grade 1 or less, and alopecia
- Non-healing wounds
- Symptomatic active bleeding
- Grade \>= 2 proteinuria as demonstrated by \>= 2+ protein and \>= 1.0 g of protein with 24-hour urine collection (patients found to have \>= 2+ protein on dipstick urinalysis must have 24-hour urine collection and demonstrate \< 1 g of protein in 24 hours in order to be eligible for the study)
- Active brain metastases or leptomeningeal metastases with the following exceptions:
- +13 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- City of Hope Medical Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
City of Hope Medical Center
Duarte, California, 91010, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Marwan G Fakih
City of Hope Medical Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 17, 2022
First Posted
November 25, 2022
Study Start
May 3, 2023
Primary Completion (Estimated)
June 23, 2026
Study Completion (Estimated)
June 23, 2026
Last Updated
November 10, 2025
Record last verified: 2025-11