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Metastatic Colon AdenocarcinomaPhase 1/2NCT05627635

FOLFOX and Bevacizumab in Combination With Botensilimab and Balstilimab (3B-FOLFOX) for the Treatment of Microsatellite Stable (MSS) Metastatic Colorectal Cancer

A Phase 1/2 study testing Balstilimab, Bevacizumab and Biospecimen Collection in people with Metastatic Colon Adenocarcinoma and Metastatic Colorectal Adenocarcinoma, run by City of Hope Medical Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Balstilimab, Bevacizumab and Biospecimen Collection
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
3 May 2023to 16 Jun 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 31Show fewer
  • 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
  • 4 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
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) (within 7 days prior to day 1 of protocol therapy)
  • Aspartate aminotransferase (AST) =< 2.5 x ULN, unless presence of liver metastases for which =< 5 x ULN is allowed (within 7 days prior to day 1 of protocol therapy)
  • Alanine aminotransferase (ALT) =< 2.5 x ULN, unless presence of liver metastases for which =< 5 x ULN is allowed (within 7 days prior to day 1 of protocol therapy)
  • Creatinine clearance >= 40 ml/min (within 7 days prior to day 1 of protocol therapy)
  • Alkaline phosphatase =< 3 x ULN (within 7 days prior to day 1 of protocol therapy)
  • Hemoglobin >= 9 g/dl (within 7 days prior to day 1 of protocol therapy)
  • Absolute neutrophil count (ANC) >= 1500/ul (within 7 days prior to day 1 of protocol therapy)
  • Platelets >= 100,000/mm^3 (within 7 days prior to day 1 of protocol therapy)
  • Albumin >= 3.0 g/dl (within 7 days prior to day 1 of protocol therapy)
  • Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (within 7 days prior to day 1 of protocol therapy)
  • If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Females of non-childbearing potential defined as:
  • >= 50 years of age and has not had menses for greater than 1 year
  • Amenorrheic for >= 2 years without a hysterectomy and bilateral oophorectomy and a follicle-stimulating hormone value in the postmenopausal range upon pre-study (screening) evaluation
  • Status is post-hysterectomy, bilateral oophorectomy, or tubal ligation
  • Women patients of reproductive potential must use effective contraception while receiving oxaliplatin and for 9 months after the final dose. Men with female partners of reproductive potential must use effective contraception while receiving oxaliplatin and for 6 months after the final dose. 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 90 days after the last dose of balstilimab and/or botensilimab

Who cannot join

  • 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
Show all 28Show fewer
  • 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:
  • Treated brain metastases require a) surgical resection, or b) stereotactic radiosurgery. These patients must be off steroids >= 10 days prior to randomization for the purpose of managing their brain metastases. Repeat brain imaging following surgical resection or stereotactic radiosurgery at least 4 weeks from treatment should document lack of progression
  • Concurrent malignancy (present during screening) requiring treatment or history of prior malignancy active within 2 years prior to the first dose of study treatment, i.e., patients with a history of prior malignancy are eligible if treatment was completed at least 2 years before the first dose of study treatment and the patient has no evidence of disease. Patients with history of prior early-stage basal/squamous cell skin cancer, low-risk prostate cancer eligible for active surveillance or noninvasive or in situ cancers who have undergone definitive treatment at any time are also eligible
  • Any evidence of current interstitial lung disease (ILD) or pneumonitis or a prior history of ILD or non-infectious pneumonitis requiring high-dose glucocorticoids
  • Psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
  • History or current evidence of any condition, co-morbidity, therapy, any active infections, or laboratory abnormality 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
  • Known previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within 10 days for mild or asymptomatic infections or 20 days for severe/critical illness prior to cycle 1 day 1 (C1D1)
  • Uncontrolled infection with human Immunodeficiency virus (HIV). Patients on stable highly active antiretroviral therapy (HAART) with undetectable viral load and normal CD4 counts for at least 6 months prior to study entry are eligible. Serological testing for HIV at screening is not required
  • Known to be positive for hepatitis B virus (HBV) surface antigen, or any other positive test for HBV indicating acute or chronic infection. Patients who are receiving or who have received anti-HBV therapy and have undetectable HBV deoxyribonucleic acid (DNA) for at least 6 months prior to study entry 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 provided they are virus-free by PCR for at least 6 months prior to study entry. Serological testing for HCV at screening is not required
  • Grade 2 or above neuropathy at the time of enrollment
  • Dependence on total parenteral nutrition or intravenous hydration
  • 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)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • City of Hope Medical Center

    Duarte, California, 91010

Other trials in United States

About this study

Official title: A Phase I/II Clinical Trial of FOLFOX Bevacizumab Plus Botensilimab and Balstilimab (3B-FOLFOX) in Patients With MSS Metastatic Colorectal Cancer

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the safety and tolerability of leucovorin calcium, fluorouracil, oxaliplatin (FOLFOX) bevacizumab, balstilimab and botensilimab at each dose level in order to inform the recommended phase 2 dose (RP2D). (Phase I) II. To assess the overall response rate of FOLFOX bevacizumab, balstilimab at 240 mg and botensilimab at 25 mg and 75 mg (depending on dose level). (Phase II)

SECONDARY OBJECTIVES:

  1. To assess the overall response rate, progression-free survival (PFS), and overall survival (OS) of FOLFOX bevacizumab, balstilimab at 240 mg and botensilimab at 25 mg and 75 mg (depending on dose level). (Phase I) II. To estimate the median PFS and median OS associated with FOLFOX bevacizumab, balstilimab at 240 mg and botensilimab at 25 mg and 75 mg botensilimab (depending on dose level). (Phase II) III. To estimate the duration of response associated with FOLFOX bevacizumab, balstilimab at 240 mg and botensilimab at 25 mg botensilimab and 75 mg (depending on dose level). (Phase II) IV. To evaluate the safety/feasibility of FOLFOX bevacizumab, botensilimab, and balstilimab, through the assessment of adverse events. (Phase II) V. To describe the rate of secondary resection in all arms of treatment and summarize their outcome in terms of disease relapse post-surgery. (Phase II)

CORRELATIVE OBJECTIVE:

  1. Evaluate potential circulating biomarkers of response, resistance, activity, and toxicity.

OUTLINE: This is a phase I, dose-escalation study of botensilimab followed by a randomized phase II study.

PHASE I: Patients receive FOLFOX, bevacizumab, balstilimab, and botensilimab intravenously (IV) on study. Patients undergo an x-ray, computed tomography (CT) scan, positron emission tomography (PET) scan, and/or magnetic resonance imaging (MRI) throughout the trial. Patients also undergo blood sample collection during screening and on study.

PHASE II: Patients are randomized to 1 of 2 arms.

ARM I: Patients 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.

ARM II: Patients 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.

Being tested
Balstilimab, Bevacizumab, Biospecimen Collection, Botensilimab, Computed Tomography
Medical subject headings
Colonic Neoplasms, Rectal Neoplasms, Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BalstilimabBiological

    Also called AGEN 2034, AGEN-2034, AGEN2034

    Given IV

  • BevacizumabBiological

    Also called ABP 215, Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF Monoclonal Antibody SIBP04

    Given IV

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo a blood sample collection

  • BotensilimabBiological

    Also called AGEN 1181, AGEN-1181, AGEN1181, Anti-CTLA-4 Monoclonal Antibody AGEN1181

    Given IV

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo a CT scan

  • FluorouracilDrug

    Also called 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione

    Given IV

  • Leucovorin CalciumDrug

    Also called Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate

    Given IV

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR

    Undergo MRI

  • OxaliplatinDrug

    Also called 1-OHP, Ai Heng, Aiheng, Dacotin

    Given IV

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan

    Undergo a PET scan

  • X-Ray ImagingProcedure or surgery

    Also called Conventional X-Ray, Diagnostic Radiology, Medical Imaging, X-Ray, Radiographic Imaging

    Undergo an x-ray

Study groups in NCT05627635
Study groupRoleWhat they receive
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.
Receives: Biological: Balstilimab; Biological: Bevacizumab; Procedure: Biospecimen Collection; Biological: Botensilimab; Procedure: Computed Tomography; Drug: Fluorouracil; Drug: Leucovorin Calcium; Procedure: Magnetic Resonance Imaging; Drug: Oxaliplatin; Procedure: Positron Emission Tomography; Procedure: X-Ray Imaging
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.
Receives: Biological: Balstilimab; Biological: Bevacizumab; Procedure: Biospecimen Collection; Biological: Botensilimab; Procedure: Computed Tomography; Drug: Fluorouracil; Drug: Leucovorin Calcium; Procedure: Magnetic Resonance Imaging; Drug: Oxaliplatin; Procedure: Positron Emission Tomography; Procedure: X-Ray Imaging
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.
Receives: Biological: Balstilimab; Biological: Bevacizumab; Procedure: Biospecimen Collection; Biological: Botensilimab; Procedure: Computed Tomography; Drug: Fluorouracil; Drug: Leucovorin Calcium; Procedure: Magnetic Resonance Imaging; Drug: Oxaliplatin; Procedure: Positron Emission Tomography; Procedure: X-Ray Imaging

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Up to 6 weeks

  2. 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.

    Measured: Up to 5 years

Secondary outcomes (8)

  1. Overall response (phase I)

    Assessed by RECIST 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.

    Measured: Up to 5 years

  2. Progression-free survival (PFS) (phase I)

    Kaplan-Meier curve will be used to assess the PFS. Median survival and the 95% confidence interval (CI) will be reported. The effect of the higher botensilimab dose (75mg versus [vs] 25mg) will be estimated by the hazard ratio (HR) in a Cox proportional hazard model with and without adjustment for clinically relevant covariates. Will examine the proportion of the liver metastasis among the 60 enrolled patients and carry out subgroup analysis for PFS for patients with and without liver metastasis.

    Measured: Time to disease progression/ relapse or death as a result of any cause, assessed up to 5 years

  3. Overall survival (OS) (phase I)

    Kaplan-Meier curve will be used to assess the OS. Median survival and the 95% CI will be reported. The effect of the higher botensilimab dose (75mg vs 25mg) will be estimated by the HR in a Cox proportional hazard model with and without adjustment for clinically relevant covariates. We will examine the proportion of the liver metastasis among the 60 enrolled patients and carry out subgroup analysis for OS for patients with and without liver metastasis.

    Measured: Time to death as a result of any cause, assessed up to 5 years

  4. PFS (phase II)

    Kaplan-Meier curve will be used to assess the PFS. Median survival and the 95% CI will be reported. The effect of the higher botensilimab dose (75mg vs 25mg) will be estimated by the HR in a Cox proportional hazard model with and without adjustment for clinically relevant covariates. Will examine the proportion of the liver metastasis among the 60 enrolled patients and carry out subgroup analysis for PFS for patients with and without liver metastasis.

    Measured: Time to disease progression or death as a result of any cause, assessed up to 5 years

  5. OS (phase II)

    Kaplan-Meier curve will be used to assess the OS. Median survival and the 95% CI will be reported. The effect of the higher botensilimab dose (75mg vs 25mg) will be estimated by the HR in a Cox proportional hazard model with and without adjustment for clinically relevant covariates. We will examine the proportion of the liver metastasis among the 60 enrolled patients and carry out subgroup analysis for OS for patients with and without liver metastasis.

    Measured: Time to death as a result of any cause, assessed up to 5 years

  6. Duration of response (phase II)

    Measured: Time to progression or death, starting at the time when a response is experienced, assessed up to 5 years

  7. Incidence of adverse events (phase II)

    Toxicity, graded according to the NCI-CTCAE v5.0.

    Measured: Up to 5 years

  8. Surgical resection (phase II)

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Nov 2022
  2. Study start3 May 2023
  3. Primary completion16 Jun 2027 (estimated)
  4. Study completion16 Jun 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05627635
Sponsor's protocol ID
22251
Other IDs
NCI-2022-09458, 22251, P30CA033572
Status last verified
Aug 2026
First submitted
17 Nov 2022
Last updated
1 Sep 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Balstilimab, Bevacizumab and Biospecimen Collection in people with Metastatic Colon Adenocarcinoma and Metastatic Colorectal Adenocarcinoma, run by City of Hope Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 31 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 1 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events (phase I) (time frame: Up to 6 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05627635.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2026.

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