Not Yet RecruitingPhase 1

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

United States30 participantsStarted 2026-07-21

Plain-language 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.

Who can participate

Age range18 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

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 alopecia) to ≤ grade 1 to prior anti-cancer therapy * ARM A ONLY: Patients should not have evidence of hepatic metastatic disease * ARM A ONLY: Patients should have progressed following irinotecan, oxaliplatin, fluoropyrimidine, and an anti-EGFR if clinically indicated * ARM B ONLY: Patient is eligible for maintenance 5-FU/LV or 5-FU/LV bevacizumab * ARM B ONLY: No history of significant toxicity to 5-FU/LV that required dose reduction in infusional 5-FU dosing * ARM C ONLY: Patient is eligible for FOLFIRI chemotherapy * ARM C ONLY: No history of significant toxicity to 5-FU/LV or irinotecan that required dose reduction in infusional 5-FU dosing or irinotecan * ARM C ONLY: No prior progression on prior irinotecan and no prior dose reduction on irinotecan due to toxicity * Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L * NOTE: no blood transfusions or growth factor therapy used within 7 da…

What they're measuring

Incidence of dose limiting toxicities

Timeframe: Up to 6 weeks or 3 doses of ivonescimab, whichever is longer

Trial details

NCT IDNCT07363408

SponsorCity of Hope Medical Center

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2027-07-21