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Not Yet RecruitingNCT07363408

Ivonescimab and ADG126, Alone, and in Combination With Leucovorin and Fluorouracil or FOLFIRI Regimen for the Treatment of Microsatellite Stable Advanced/Metastatic Colorectal Cancer

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

Status
Not Yet Recruiting
Phase
Phase 1
Study type
Interventional
Enrollment
30 (estimated)
Sponsor
City of Hope Medical Center · Academic / Other
Sex
All
Age
18 Years
Healthy volunteers
Not accepted

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.

Detailed 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 ADG126 with ivonescimab, and in combination with 5-FU/LV, and in combination with FOLFIRI in MSS advanced/metastatic colorectal cancer. II. Describe the overall response rate (ORR) as evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for the three treatment arms individually. III. Describe the duration of response (DoR), progression free survival (PFS), and overall survival (OS) of each of the three treatment arms. IV. Assess ADG126 pharmacokinetics (PK) through sparse sampling at different doses of ADG126 on study and in combination with ivonescimab, 5-FU/LV, or FOLFIRI. EXPLORATORY OBJECTIVE: I. Explore the dynamics of immune cells in relation to clinical outcome by treatment arm, which include the data from immunophenotyping, cytokine analysis and ribonucleic acid (RNA) sequencing of peripheral blood and buffy coat at baseline, 4 weeks, and 8 weeks, and every subsequent 8 weeks until progression. OUTLINE: This is a dose-escalation study of muzastotug in combination with ivonescimab, leucovorin, fluorouracil, and irinotecan. Patients are assigned to 1 of 3 arms. ARM A: Patients receive muzastotug intravenously (IV) over 60-90 minutes on day 1 of each cycle and ivonescimab IV over 60 minutes on days 1, 15, and 29 of each cycle. Cycles repeat every 6 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI), and collection of blood samples throughout the study. ARM B: Patients receive muzastotug IV over 60-90 minutes on day 1 of each cycle, ivonescimab IV over 60 minutes on days 1, 15, and 29 of each cycle, leucovorin IV over 2 hours on days 1, 15, and 29 of each cycle, and fluorouracil IV continuously over 46 hours on days 1, 15, and 29 of each cycle. Cycles repeat every 6 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI, and collection of blood samples throughout the study. ARM C: Patients receive muzastotug IV over 60-90 minutes on day 1 of each cycle, ivonescimab IV over 60 minutes on days 1, 15, and 29 of each cycle, leucovorin IV over 2 hours on days 1, 15, and 29 of each cycle, fluorouracil IV continuously over 46 hours on days 1, 15, and 29 of each cycle, and irinotecan IV over 90 minutes on day 1 of each cycle. Cycles repeat every 6 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI, and collection of blood samples throughout the study. After completion of study treatment, patients are followed for 30 days, every 3 months until disease progression (if applicable) for 2 years and/or after disease progression periodically for survival.

Conditions

Interventions

TypeNameDescription
PROCEDUREBiospecimen CollectionUndergo blood sample collection
PROCEDUREComputed TomographyUndergo CT
DRUGFluorouracilGiven IV
DRUGIrinotecanGiven IV
BIOLOGICALIvonescimabGiven IV
DRUGLeucovorin CalciumGiven IV
PROCEDUREMagnetic Resonance ImagingUndergo MRI
BIOLOGICALMuzastotugGiven IV

Timeline

Start date
2026-07-21
Primary completion
2027-07-21
Completion
2027-07-21
First posted
2026-01-23
Last updated
2026-01-23

Locations

1 site across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT07363408. Inclusion in this directory is not an endorsement.