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

Conditions

• Advanced Microsatellite Stable Colorectal Carcinoma
• Metastatic Microsatellite Stable Colorectal Carcinoma
• Stage III Colorectal Cancer AJCC v8
• Stage IV Colorectal Cancer AJCC v8

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Biospecimen Collection — PROCEDURE
  Undergo blood sample collection
• Computed Tomography — PROCEDURE
  Undergo CT
• Fluorouracil — DRUG
  Given IV
• Irinotecan — DRUG
  Given IV
• Ivonescimab — BIOLOGICAL
  Given IV
• Leucovorin Calcium — DRUG
  Given IV
• Magnetic Resonance Imaging — PROCEDURE
  Undergo MRI
• Muzastotug — BIOLOGICAL
  Given IV

Study Details

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.

Key Dates

Start date

Jul 21, 2026

Status verified

Jan 2026

Primary completion

Jul 21, 2027

Completion

Jul 21, 2027

Study Design

Enrollment

30 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: Arm A (muzastotug, ivonescimab)
  Patients receive muzastotug 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 CT or MRI, and collection of blood samples throughout the study.
• Experimental: Arm B (muzastotug, ivonescimab, leucovorin, fluorouracil)
  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.
• Experimental: Arm C (muzastotug, ivonescimab, FOLFIRI)
  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.

Primary Outcome Measure

Incidence of dose limiting toxicities [ Time Frame: Up to 6 weeks or 3 doses of ivonescimab, whichever is longer ]

Locations (1)

Find similar trials in Duarte, CA

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