A Phase 2 Study of Microsatellite Stable Colorectal Cancer (Stage 2 or 3) With Radiographic Occult Molecular Residual Disease Treated With Botensilimab (AGEN1181; Bot) Plus Balstilimab (AGEN2034, Bal) After Established Definitive Therapy (COMBAT Study)
Overview
- Phase
- Phase 2
- Status
- Not yet recruiting
- Enrollment
- 20
- Primary Endpoint
- Circulating tumor deoxyribonucleic acid (ctDNA) clearance
Overview
Brief Summary
This phase II trial tests the effect of the botensilimab in combination with balstilimab in treating patients with stage II/III colorectal adenocarcinoma with detectable circulating tumor (ct) deoxyribonucleic acid (DNA) in the blood. Immunotherapy with monoclonal antibodies, such as botensilimab and balstilimab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Giving botensilimab and balstilimab may be an effective combination to remove any remaining microscopic cancer cells in the bloodstream in patients with stage II/III colorectal adenocarcinoma. In addition, clearing the ctDNA from the blood may serve as an early indicator of treatment response.
Detailed Description
PRIMARY OBJECTIVE:
I. To determine the 6-month circulating tumor DNA (ctDNA) clearance rate following 6 months of therapy with botensilimab (AGEN1181) and balstilimab (AGEN2034) regimen in patients with colorectal cancer (CRC) who present with radiographic occult molecular residual disease (MRD) after completing definitive standard-of-care (SOC) therapy.
SECONDARY OBJECTIVES:
I. To determine the 3-month ctDNA clearance rate following botensilimab (AGEN1181) and balstilimab (AGEN2034) treatment.
II. To determine recurrence-free survival (RFS) at 1-year following 6 months of botensilimab (AGEN1181) and balstilimab (AGEN2034) treatment.
III. To determine overall survival (OS) at 1-year following 6 months of botensilimab (AGEN1181) and balstilimab (AGEN2034) treatment.
IV. To determine the safety and tolerability of botensilimab (AGEN1181) and balstilimab (AGEN2034).
V. To determine if Cancer Immunotherapy Response Classifier (CIRCLE) in archival tumor (using whole exome sequencing [WES]) may predict clinical benefit of botensilimab (AGEN1181) plus balstilimab (AGEN2034) in MRD CRC.
EXPLORATORY OBJECTIVES:
I. To determine changes in profiles of ctDNA (including time to ctDNA negative status, duration of ctDNA negative status, overall ctDNA negative rate, lead time from ctDNA detection to radiographic detection) during and following treatment with botensilimab (AGEN1181) and balstilimab (AGEN2034).
II. To determine baseline characteristics in archival tumor and/or plasma that may predict clinical benefit or lack thereof.
OUTLINE:
Patients receive balstilimab intravenously (IV) over 30 minutes on days 1 and 22 of cycles 1-4 and botensilimab IV over 30 minutes on days 1 of cycles 1 and 2. Treatment repeats every 42 days for up to 4 cycles (6 months) in the absence of disease progression or unacceptable toxicity. Patients also undergo urine and blood sample collection and imaging throughout the study. Additionally, patients may undergo optional tumor tissue biopsy on study.
After completion of study treatment, patients are followed for up to 90 days, every 3 months during the first year, every 4 months during the second year, then every 6 months during the third year unless recurrence of tumor or death occurs.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of botensilimab (AGEN1181) in combination with balstilimab (AGEN2034) in patients \< 18 years of age, children are excluded from this study
- •Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 (or Karnofsky ≥ 60%)
- •Absolute neutrophil count ≥ 1,000/mcL
- •Platelets ≥ 100,000/mcL
- •Total bilirubin ≤ 1.5 x the institutional upper limit of normal (ULN)
- •Patients with documented Gilbert's syndrome may be included if total bilirubin is ≤ 3 x ULN
- •Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 x institutional ULN
- •Creatinine clearance ≥ 40 mL/min
- •Creatinine clearance (Clcr) can either be measured in a 24-hour urine collection or estimated by the Cockcroft-Gault equation
- •Histological confirmation of colorectal cancer (adenocarcinoma) (CRC)
Exclusion Criteria
- •Patients who are receiving any other investigational agents
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to botensilimab (AGEN1181) and balstilimab (AGEN2034)
- •Patients that are pregnant, breast feeding, or planning to become pregnant while enrolled in the study, up to the end of treatment (EOT) visit, are excluded from this study because botensilimab (AGEN1181) and balstilimab (AGEN2034) are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with botensilimab (AGEN1181) and balstilimab (AGEN2034), breastfeeding should be discontinued if the mother is treated with botensilimab (AGEN1181) and balstilimab (AGEN2034)
- •Patients with microsatellite instability (MSI-high) or deficient mismatch repair (dMMR) CRC (MMR/MSI testing is required prior to enrollment)
- •Concurrent treatment with a drug with which the interactions are considered clinically significant by the investigator. Major surgical procedure or significant traumatic injury within 21 days before start of study medication \* Note: If participants received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
- •Systemic therapy with immunosuppressive agents within 7 days or use of any investigational drug within 28 days before the start of trial treatment
- •Prior exposure to any immune checkpoint blockade agent or any other immunomodulatory agent used for antineoplastic therapy for metastatic (m)CRC
- •Receipt of any organ transplantation, including allogeneic stem cell transplantation (exception: transplants that do not require immunosuppression, such as hair transplant)
- •Patients with active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
- •Patients with known severe hypersensitivity reactions to monoclonal antibodies (grade ≥ 3 National Cancer Institute \[NCI\]-Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\] 5.0), any history of anaphylaxis, or recent (within 5 months) history of uncontrolled asthma
Arms & Interventions
Treatment (balstilimab, botensilimab)
Patients receive balstilimab IV over 30 minutes on days 1 and 22 of cycles 1-4 and botensilimab IV over 30 minutes on days 1 of cycles 1 and 2. Treatment repeats every 42 days for up to 4 cycles (6 months) in the absence of disease progression or unacceptable toxicity. Patients also undergo urine and blood sample collection and imaging throughout the study. Additionally, patients may undergo optional tumor tissue biopsy on study.
Intervention: Balstilimab (Biological)
Treatment (balstilimab, botensilimab)
Patients receive balstilimab IV over 30 minutes on days 1 and 22 of cycles 1-4 and botensilimab IV over 30 minutes on days 1 of cycles 1 and 2. Treatment repeats every 42 days for up to 4 cycles (6 months) in the absence of disease progression or unacceptable toxicity. Patients also undergo urine and blood sample collection and imaging throughout the study. Additionally, patients may undergo optional tumor tissue biopsy on study.
Intervention: Biopsy Procedure (Procedure)
Treatment (balstilimab, botensilimab)
Patients receive balstilimab IV over 30 minutes on days 1 and 22 of cycles 1-4 and botensilimab IV over 30 minutes on days 1 of cycles 1 and 2. Treatment repeats every 42 days for up to 4 cycles (6 months) in the absence of disease progression or unacceptable toxicity. Patients also undergo urine and blood sample collection and imaging throughout the study. Additionally, patients may undergo optional tumor tissue biopsy on study.
Intervention: Biospecimen Collection (Procedure)
Treatment (balstilimab, botensilimab)
Patients receive balstilimab IV over 30 minutes on days 1 and 22 of cycles 1-4 and botensilimab IV over 30 minutes on days 1 of cycles 1 and 2. Treatment repeats every 42 days for up to 4 cycles (6 months) in the absence of disease progression or unacceptable toxicity. Patients also undergo urine and blood sample collection and imaging throughout the study. Additionally, patients may undergo optional tumor tissue biopsy on study.
Intervention: Botensilimab (Biological)
Treatment (balstilimab, botensilimab)
Patients receive balstilimab IV over 30 minutes on days 1 and 22 of cycles 1-4 and botensilimab IV over 30 minutes on days 1 of cycles 1 and 2. Treatment repeats every 42 days for up to 4 cycles (6 months) in the absence of disease progression or unacceptable toxicity. Patients also undergo urine and blood sample collection and imaging throughout the study. Additionally, patients may undergo optional tumor tissue biopsy on study.
Intervention: Radiographic Examination (Procedure)
Outcomes
Primary Outcomes
Circulating tumor deoxyribonucleic acid (ctDNA) clearance
Time Frame: Up to 6 months
Will be defined as clearance of ctDNA and no radiographic evidence of disease. Will estimate clearance rate and its 95% confidence interval.
Secondary Outcomes
- ctDNA clearance rate(At 3 months)
- Recurrence-free survival (RFS)(From the start of botensilimab (AGEN1181) and balstilimab (AGEN2034) to recurrence of tumor or death, whichever occurred first, assessed up to 3 years)
- Overall survival (OS)(From the first dose of study treatment to the date of death from any cause, assessed up to 3 years)
- Incidence and severity of adverse events (AEs)(Up to 90 days after last dose of study treatment)
- Determination if Cancer Immunotherapy Response Classifier may predict benefit(Up to 3 years)