Trial Title:
FOLFOX and Bevacizumab in Combination With Botensilimab and Balstilimab (3B-FOLFOX) for the Treatment of Microsatellite Stable (MSS) Metastatic Colorectal Cancer
NCT ID:
NCT05627635
Condition:
Metastatic Colon Adenocarcinoma
Metastatic Colorectal Adenocarcinoma
Metastatic Microsatellite Stable Colorectal Carcinoma
Metastatic Rectal Adenocarcinoma
Stage IV Colon Cancer AJCC v8
Stage IV Colorectal Cancer AJCC v8
Stage IV Rectal Cancer AJCC v8
Conditions: Official terms:
Colorectal Neoplasms
Adenocarcinoma
Colonic Neoplasms
Calcium, Dietary
Leucovorin
Folic Acid
Bevacizumab
Antineoplastic Agents, Immunological
Oxaliplatin
Fluorouracil
Endothelial Growth Factors
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunoglobulin G
Calcium
Levoleucovorin
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Balstilimab
Description:
Given IV
Arm group label:
Phase I (3B-FOLFOX)
Arm group label:
Phase II, Arm I (3B-FOLFOX)
Arm group label:
Phase II, Arm II (3B-FOLFOX)
Other name:
AGEN 2034
Other name:
AGEN-2034
Other name:
AGEN2034
Intervention type:
Biological
Intervention name:
Bevacizumab
Description:
Given IV
Arm group label:
Phase I (3B-FOLFOX)
Arm group label:
Phase II, Arm I (3B-FOLFOX)
Arm group label:
Phase II, Arm II (3B-FOLFOX)
Other name:
ABP 215
Other name:
Anti-VEGF
Other name:
Anti-VEGF Humanized Monoclonal Antibody
Other name:
Anti-VEGF Monoclonal Antibody SIBP04
Other name:
Anti-VEGF rhuMAb
Other name:
Avastin
Other name:
Bevacizumab awwb
Other name:
Bevacizumab Biosimilar ABP 215
Other name:
Bevacizumab Biosimilar BEVZ92
Other name:
Bevacizumab Biosimilar BI 695502
Other name:
Bevacizumab Biosimilar CBT 124
Other name:
Bevacizumab Biosimilar CT-P16
Other name:
Bevacizumab Biosimilar FKB238
Other name:
Bevacizumab Biosimilar GB-222
Other name:
Bevacizumab Biosimilar HD204
Other name:
Bevacizumab Biosimilar HLX04
Other name:
Bevacizumab Biosimilar IBI305
Other name:
Bevacizumab Biosimilar LY01008
Other name:
Bevacizumab Biosimilar MIL60
Other name:
Bevacizumab Biosimilar Mvasi
Other name:
Bevacizumab Biosimilar MYL-1402O
Other name:
Bevacizumab Biosimilar QL 1101
Other name:
Bevacizumab Biosimilar RPH-001
Other name:
Bevacizumab Biosimilar SCT501
Other name:
Bevacizumab Biosimilar Zirabev
Other name:
Bevacizumab-awwb
Other name:
Bevacizumab-bvzr
Other name:
BP102
Other name:
BP102 Biosimilar
Other name:
HD204
Other name:
Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer
Other name:
Mvasi
Other name:
MYL-1402O
Other name:
Recombinant Humanized Anti-VEGF Monoclonal Antibody
Other name:
rhuMab-VEGF
Other name:
SCT501
Other name:
SIBP 04
Other name:
SIBP-04
Other name:
SIBP04
Other name:
Zirabev
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo a blood sample collection
Arm group label:
Phase I (3B-FOLFOX)
Arm group label:
Phase II, Arm I (3B-FOLFOX)
Arm group label:
Phase II, Arm II (3B-FOLFOX)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Biological
Intervention name:
Botensilimab
Description:
Given IV
Arm group label:
Phase I (3B-FOLFOX)
Arm group label:
Phase II, Arm I (3B-FOLFOX)
Arm group label:
Phase II, Arm II (3B-FOLFOX)
Other name:
AGEN 1181
Other name:
AGEN-1181
Other name:
AGEN1181
Other name:
Anti-CTLA-4 Monoclonal Antibody AGEN1181
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo a CT scan
Arm group label:
Phase I (3B-FOLFOX)
Arm group label:
Phase II, Arm I (3B-FOLFOX)
Arm group label:
Phase II, Arm II (3B-FOLFOX)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized Tomography
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Drug
Intervention name:
Fluorouracil
Description:
Given IV
Arm group label:
Phase I (3B-FOLFOX)
Arm group label:
Phase II, Arm I (3B-FOLFOX)
Arm group label:
Phase II, Arm II (3B-FOLFOX)
Other name:
5 Fluorouracil
Other name:
5 Fluorouracilum
Other name:
5 FU
Other name:
5-Fluoro-2,4(1H, 3H)-pyrimidinedione
Other name:
5-Fluorouracil
Other name:
5-Fluracil
Other name:
5-Fu
Other name:
5FU
Other name:
AccuSite
Other name:
Carac
Other name:
Fluoro Uracil
Other name:
Fluouracil
Other name:
Flurablastin
Other name:
Fluracedyl
Other name:
Fluracil
Other name:
Fluril
Other name:
Fluroblastin
Other name:
Ribofluor
Other name:
Ro 2-9757
Other name:
Ro-2-9757
Intervention type:
Drug
Intervention name:
Leucovorin Calcium
Description:
Given IV
Arm group label:
Phase I (3B-FOLFOX)
Arm group label:
Phase II, Arm I (3B-FOLFOX)
Arm group label:
Phase II, Arm II (3B-FOLFOX)
Other name:
Adinepar
Other name:
Calcifolin
Other name:
Calcium (6S)-Folinate
Other name:
Calcium Folinate
Other name:
Calcium Leucovorin
Other name:
Calfolex
Other name:
Calinat
Other name:
Cehafolin
Other name:
Citofolin
Other name:
Citrec
Other name:
Citrovorum Factor
Other name:
Cromatonbic Folinico
Other name:
Dalisol
Other name:
Disintox
Other name:
Divical
Other name:
Ecofol
Other name:
Emovis
Other name:
Factor, Citrovorum
Other name:
Flynoken A
Other name:
Folaren
Other name:
Folaxin
Other name:
FOLI-cell
Other name:
Foliben
Other name:
Folidan
Other name:
Folidar
Other name:
Folinac
Other name:
Folinate Calcium
Other name:
folinic acid
Other name:
Folinic Acid Calcium Salt Pentahydrate
Other name:
Folinoral
Other name:
Folinvit
Other name:
Foliplus
Other name:
Folix
Other name:
Imo
Other name:
Lederfolat
Other name:
Lederfolin
Other name:
Leucosar
Other name:
leucovorin
Other name:
Rescufolin
Other name:
Rescuvolin
Other name:
Tonofolin
Other name:
Wellcovorin
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Phase I (3B-FOLFOX)
Arm group label:
Phase II, Arm I (3B-FOLFOX)
Arm group label:
Phase II, Arm II (3B-FOLFOX)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Intervention type:
Drug
Intervention name:
Oxaliplatin
Description:
Given IV
Arm group label:
Phase I (3B-FOLFOX)
Arm group label:
Phase II, Arm I (3B-FOLFOX)
Arm group label:
Phase II, Arm II (3B-FOLFOX)
Other name:
1-OHP
Other name:
Ai Heng
Other name:
Aiheng
Other name:
Dacotin
Other name:
Dacplat
Other name:
Diaminocyclohexane Oxalatoplatinum
Other name:
Eloxatin
Other name:
Eloxatine
Other name:
JM-83
Other name:
Oxalatoplatin
Other name:
Oxalatoplatinum
Other name:
RP 54780
Other name:
RP-54780
Other name:
SR-96669
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo a PET scan
Arm group label:
Phase I (3B-FOLFOX)
Arm group label:
Phase II, Arm I (3B-FOLFOX)
Arm group label:
Phase II, Arm II (3B-FOLFOX)
Other name:
Medical Imaging, Positron Emission Tomography
Other name:
PET
Other name:
PET Scan
Other name:
Positron Emission Tomography Scan
Other name:
Positron-Emission Tomography
Other name:
proton magnetic resonance spectroscopic imaging
Other name:
PT
Intervention type:
Procedure
Intervention name:
X-Ray Imaging
Description:
Undergo an x-ray
Arm group label:
Phase I (3B-FOLFOX)
Arm group label:
Phase II, Arm I (3B-FOLFOX)
Arm group label:
Phase II, Arm II (3B-FOLFOX)
Other name:
Conventional X-Ray
Other name:
Diagnostic Radiology
Other name:
Medical Imaging, X-Ray
Other name:
Radiographic Imaging
Other name:
Radiography
Other name:
RG
Other name:
Static X-Ray
Other name:
X-Ray
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.
Detailed description:
PRIMARY OBJECTIVES:
I. 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:
I. 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:
I. 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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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
- 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
Exclusion Criteria:
- 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:
- 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)
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
City of Hope Medical Center
Address:
City:
Duarte
Zip:
91010
Country:
United States
Status:
Recruiting
Contact:
Last name:
Marwan G. Fakih
Phone:
626-256-4673
Email:
mfakih@coh.org
Investigator:
Last name:
Marwan G. Fakih
Email:
Principal Investigator
Start date:
May 3, 2023
Completion date:
October 7, 2025
Lead sponsor:
Agency:
City of Hope Medical Center
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
City of Hope Medical Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05627635
