Trial Title:
Botensilimab, Balstilimab and Regorafenib for the Treatment of Patients with Microsatellite Stable Metastatic Colorectal Cancer Who Have Progressed on Prior Chemotherapy
NCT ID:
NCT05672316
Condition:
Advanced Colorectal Adenocarcinoma
Advanced Microsatellite Stable Colorectal Carcinoma
Metastatic Colorectal Adenocarcinoma
Metastatic Microsatellite Stable Colorectal Carcinoma
Stage III Colorectal Cancer AJCC V8
Stage IV Colorectal Cancer AJCC V8
Conditions: Official terms:
Carcinoma
Colorectal Neoplasms
Adenocarcinoma
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Balstilimab
Description:
Given IV
Arm group label:
Treatment (botensilimab, balstilimab and regorafenib)
Other name:
AGEN 2034
Other name:
AGEN-2034
Other name:
AGEN2034
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo collection of blood
Arm group label:
Treatment (botensilimab, balstilimab and regorafenib)
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:
Treatment (botensilimab, balstilimab and regorafenib)
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 CT
Arm group label:
Treatment (botensilimab, balstilimab and regorafenib)
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:
Regorafenib
Description:
Given PO
Arm group label:
Treatment (botensilimab, balstilimab and regorafenib)
Other name:
BAY 73-4506
Other name:
Regorafenib Anhydrous
Summary:
This phase I/II trial tests how well botensilimab, balstilimab, and regorafenib works in
treating patients with microsatellite stable colorectal cancer that has spread from where
it first started (primary site) to other places in the body (metastatic) or that may have
spread from where it first started to nearby tissue, lymph nodes, or distant parts of the
body (advanced) and who have progressed on prior chemotherapy. Immunotherapy with
monoclonal antibodies, such as botensilimab and balstilimab, may help the body's immune
system attack the cancer, and may interfere with the ability of tumor cells to grow and
spread. Regorafenib binds to and inhibits growth factor receptors, which may inhibit the
growth of new blood vessels that tumors need to grow. Giving botensilimab, balstilimab,
and regorafenib in combination may work better in treating patients with metastatic
colorectal cancer than giving these drugs alone.
Detailed description:
PRIMARY OBJECTIVES:
I. To identify the recommended phase 2 dose (RP2D) of botensilimab, balstilimab, and
regorafenib (BBR) in patients with chemotherapy-resistant microsatellite stable (MSS)
metastatic colorectal cancer (MSS mCRC). (Phase I) II. To estimate the overall response
rate (ORR) of botensilimab, balstilimab, and regorafenib in patients with
chemotherapy-resistant MSS mCRC, with and without liver metastatic disease. (Phase II)
SECONDARY OBJECTIVES:
I. Describe the safety of botensilimab, balstilimab, and regorafenib at all evaluable
dose levels. (Phase I) II. Describe the efficacy of BBR in terms of ORR, progression free
survival (PFS) and overall survival (OS). (Phase I) III. To evaluate the
safety/feasibility of botensilimab, balstilimab, and regorafenib through the assessment
of adverse events. (Phase II) IV. Estimate the PFS, OS and duration of response (DOR).
(Phase II)
CORRELATIVE OBJECTIVES:
I. Evaluate potential circulating biomarkers of response, resistance, activity, and
toxicity. (Phase I/II) II. Correlate baseline molecular biomarkers (RAS, BRAF, TMB, and
PD-L1 if available), with overall outcome. (Phase I/II)
OUTLINE: This is a phase I, dose-escalation study of botensilimab followed by a phase II
study.
Patients receive botensilimab intravenously (IV), balstilimab IV, and regorafenib orally
(PO) on study. Patients also undergo computed tomography (CT) and collection of blood
throughout the 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
- Able to swallow and absorb oral tablets
- Histological or cytological confirmed advanced, metastatic, or progressive
proficient mismatch repair (pMMR)/MSS adenocarcinoma of colon or rectum
- Microsatellite status should be performed per local standard of practice (e.g.,
immunohistochemistry [IHC] and/or polymerase chain reaction [PCR], or
next-generation sequencing). Only participants with pMMR/MSS mCRC are eligible
- Patients should have measurable metastatic disease as per Response Evaluation
Criteria in Solid Tumors (RECIST) 1.1 guidelines
- Known extended RAS and BRAF status as per local standard of practice. TMB and PD-L1
status will be collected when available but not mandated for enrollment
- Patients must have progressed following exposure to all of the following agents:
- Fluoropyrimidines (capecitabine or 5-FU)
- Irinotecan
- Oxaliplatin
- Anti-EGFR therapy if RAS and BRAF wild type with left colon primary
- Patients must have evidence of progression on or after the last treatment received
and within 6 months prior to study enrollment
- Patients who were intolerant to prior systemic chemotherapy regimens are
eligible if there is documented evidence of clinically significant intolerance
despite adequate supportive measures
- Adjuvant/neoadjuvant chemotherapy can be considered as one line of chemotherapy
for advanced/metastatic disease if the participant had disease recurrence
within 6 months of completion
- For patients with liver metastatic disease, patients must have no more than 5
hepatic metastases at the time of enrollment
- Patients without liver metastatic disease should be either with no history of liver
metastatic disease or with history of resected or ablated liver metastases without
evidence of disease recurrence in the liver for at least 6 months before enrollment
- Total bilirubin =< 1.5 x upper limit of normal (ULN) (to be performed within 7 days
prior to day 1 of protocol therapy unless otherwise stated)
- Aspartate aminotransferase (AST) =< 2.5 x ULN, unless presence of liver metastases
for which =< 5 x ULN is allowed (to be performed within 7 days prior to day 1 of
protocol therapy unless otherwise stated)
- Alanine aminotransferase (ALT) =< 2.5 x ULN, unless presence of liver metastases for
which =< 5 x ULN is allowed (to be performed within 7 days prior to day 1 of
protocol therapy unless otherwise stated)
- Serum creatinine =< 1.5 x ULN or creatinine clearance >= 40 mL/min (measured or
calculated using the Cockcroft-Gault formula) (to be performed within 7 days prior
to day 1 of protocol therapy unless otherwise stated)
- White blood cell (WBC) >= 2000/ul (to be performed within 7 days prior to day 1 of
protocol therapy unless otherwise stated)
- Hemoglobin >= 9 g/dl (to be performed within 7 days prior to day 1 of protocol
therapy unless otherwise stated)
- Absolute neutrophil count (ANC) >= 1500/ul (to be performed within 7 days prior to
day 1 of protocol therapy unless otherwise stated)
- Platelets >= 75,000/mm^3 (to be performed within 7 days prior to day 1 of protocol
therapy unless otherwise stated)
- Albumin >= 3.0 g/dl (to be performed within 7 days prior to day 1 of protocol
therapy unless otherwise stated)
- Women of childbearing potential (WOCBP): negative urine or serum pregnancy test. If
the urine test is positive or cannot be confirmed as negative, a serum pregnancy
test will be required (to be performed within 7 days prior to day 1 of protocol
therapy unless otherwise stated)
- Agreement by females and males of childbearing potential to use an effective method
of birth control or abstain from sexual activity for the course of the study through
at least 120 days after the last dose of protocol therapy
- 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
Exclusion Criteria:
- Prior immunotherapy with PD-1 or PD-L1 or CTLA-4 targeting agents
- 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
- 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 non-colorectal second malignancy (present during screening) requiring
treatment or history of a non-colorectal second primary metastatic malignancy within
2 years prior to the first dose of study treatment. 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 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
- 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
Start date:
May 11, 2023
Completion date:
October 27, 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/NCT05672316
