A Phase I Clinical Trial of Ivonescimab and ADG126, Alone, and in Combination With 5-FU/LV or FOLFIRI in MSS Advanced/Metastatic Colorectal Cancer
City of Hope Medical Center
Summary
This phase I trial studies the safety, side effects, and best dose of ADG126, in combination with ivonescimab alone, in combination with ivonescimab, leucovorin, and fluorouracil, or in combination with ivonescimab and leucovorin, fluorouracil, and irinotecan (FOLFIRI regimen) in treating patients with microsatellite stable (MSS) colorectal cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or has spread from where it first started (primary site) to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as ivonescimab and ADG126, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Ivonescimab may also stop or slow the cancer by blocking the growth of new blood vessels necessary for tumor growth. Leucovorin calcium is a type of drug called a folic acid analog, which means it is similar to the vitamin folic acid. It is used in combination with certain chemotherapy drugs to enhance their ability to kill tumor cells or to lessen their harmful side effects. Fluorouracil is a type of chemotherapy called an antimetabolite, which is a drug that mimics a natural chemical and prevents its use in cells. It interferes with the production of a key component of deoxyribonucleic acid (DNA), which prevents the DNA from copying itself. This causes tumor cells and other rapidly dividing cells to die. Fluorouracil also gets incorporated into ribonucleic acid (RNA) and DNA, disrupting critical cell functions. Irinotecan is in a class of antineoplastic medications called topoisomerase I inhibitors. It blocks a certain enzyme needed for cell division and DNA repair and may kill cancer cells. Giving ADG126 with ivonescimab, with or without leucovorin and fluorouracil or FOLFIRI regimen, may be safe in treating patients with MSS advanced/metastatic colorectal cancer.
Description
PRIMARY OBJECTIVES: I. Determine the recommended phase II dose of muzastotug (ADG126) and ivonescimab (Arm A) in advanced/metastatic MSS colorectal cancer without liver metastatic disease. II. Determine the recommended phase II dose of ADG126 and ivonescimab with fluorouracil (5-FU)/leucovorin (LV) (Arm B) in advanced/metastatic MSS colorectal cancer. III. Determine the recommended phase II dose of ADG126 and ivonescimab with leucovorin, fluorouracil, and irinotecan (FOLFIRI) (Arm C) in advanced/metastatic MSS colorectal cancer. SECONDARY OBJECTIVES: I. Describe the safety of giving ADG12…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Documented informed consent of the participant and/or legally authorized representative * Agreement to blood collection for correlative analysis at baseline, 4 weeks, and 8 weeks, and then every subsequent 8 weeks * Age: ≥ 18 years * Eastern Cooperative Oncology Group (ECOG) ≤ 1 * Histologically confirmed advanced/metastatic MSS colorectal cancer. MSS status must have been confirmed by a Clinical Laboratory Improvement Amendments (CLIA) certified assay * Measurable disease by RECIST 1.1 * Fully recovered from the acute, clinically significant, toxic effects (except alope…
Interventions
- ProcedureBiospecimen Collection
Undergo blood sample collection
- ProcedureComputed Tomography
Undergo CT
- DrugFluorouracil
Given IV
- DrugIrinotecan
Given IV
- BiologicalIvonescimab
Given IV
- DrugLeucovorin Calcium
Given IV
- ProcedureMagnetic Resonance Imaging
Undergo MRI
Location
- City of Hope Medical CenterDuarte, California