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
3 other identifiers
interventional
30
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Jul 2026
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 22, 2026
CompletedFirst Posted
Study publicly available on registry
January 23, 2026
CompletedStudy Start
First participant enrolled
July 21, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
July 21, 2027
Study Completion
Last participant's last visit for all outcomes
July 21, 2027
January 23, 2026
January 1, 2026
1 year
January 22, 2026
January 22, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Incidence of dose limiting toxicities
Will be assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, by treatment arm. Descriptive statistics will be used for all safety, efficacy and immunogenicity parameters. Data will be summarized using descriptive statistics (number of subjects, mean, median, standard deviation, minimum, and maximum) for continuous variables and using frequencies and percentages for categorical variables. Differences among groups will be tested using the Fisher's exact test and Kruskal-Wallis test for categorical and continuous variables, respectively.
Up to 6 weeks or 3 doses of ivonescimab, whichever is longer
Secondary Outcomes (6)
Treatment-related adverse event rates
Up to 30 days after completion of study treatment
Objective response rate
From the start of the study treatment and disease progression or death due to any cause prior to receiving another therapy, whichever occurs first, assessed up to 2 years after completion of study treatment
Duration of response
From the time when a response is experienced to progression or death, assessed up to 2 years after completion of study treatment
Progression-free survival
From the start of treatment to disease progression or death from any cause, whichever occurs first, assessed up to 2 years after completion of study treatment
Overall survival
From start of treatment to death due to any cause, assessed up to 2 years after completion of study treatment
- +1 more secondary outcomes
Study Arms (3)
Arm A (muzastotug, ivonescimab)
EXPERIMENTALPatients 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.
Arm B (muzastotug, ivonescimab, leucovorin, fluorouracil)
EXPERIMENTALPatients 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 (muzastotug, ivonescimab, FOLFIRI)
EXPERIMENTALPatients 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.
Interventions
Given IV
Undergo MRI
Given IV
Undergo blood sample collection
Undergo CT
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- 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
- +19 more criteria
You may not qualify if:
- Major surgical procedures or serious trauma within 4 weeks prior to study entry, or plans for major surgical procedures within 4 weeks after the first dose (as determined by the investigator). Minor local procedures (excluding central venous catheterization and port implantation) within 3 days prior to study entry
- Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation
- Chemotherapy, radiation therapy, biological therapy, immunotherapy within 21 days or five half-lives (whichever is shorter for non-radiation therapy) prior to day 1 of protocol therapy
- Strong CYP3A4 inducers/ inhibitors within 14 days prior to day 1 of protocol therapy (Arm C only)
- UGT1A1 inhibitors within 14 days prior to day 1 of protocol therapy (Arm C only)
- Any other anti-cancer therapy is prohibited, including but not limited to antibody-based therapy, retinoids, nitrosourea therapy, mitomycin C, small molecule tyrosine kinase inhibitors, proprietary Chinese medicines with anti-cancer activity, or radiotherapy
- Herbal medications must be cleared by the principal investigator (PI)
- Prior exposure to PD-1 or PD-L1 or CTLA-4 targeting agents
- History of bleeding tendencies or coagulopathy and/or clinically significant bleeding symptoms or risk within 4 weeks prior to study entry, including but not limited to:
- Hemoptysis (defined as coughing up ≥ 0.5 teaspoon of fresh blood or small blood clots) Note: transient hemoptysis associated with diagnostic bronchoscopy is allowed
- Nasal bleeding/epistaxis (bloody nasal discharge is allowed)
- Current use of prophylactic or full-dose anticoagulants or anti-platelet agents for therapeutic purposes that is not stable prior to study entry is not allowed. The use of full-dose anticoagulants is permitted as long as the international normalized ratio (INR) or activated partial thromboplastin time (aPTT) is within therapeutic limits according to the medical standard of the enrolling institution or with the use of factor Xa inhibitors
- Poorly controlled hypertension with repeated systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg after oral antihypertensive therapy
- Active autoimmune or lung disease requiring systemic therapy (eg, with disease modifying drugs, prednisone \> 10 mg daily or equivalent, immunosuppressant therapy) within 2 years prior to study entry, however the following will be allowed:
- Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is permitted.
- +29 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- City of Hope Medical Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
City of Hope Medical Center
Duarte, California, 91010, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Marwan G Fakih
City of Hope Medical Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 22, 2026
First Posted
January 23, 2026
Study Start (Estimated)
July 21, 2026
Primary Completion (Estimated)
July 21, 2027
Study Completion (Estimated)
July 21, 2027
Last Updated
January 23, 2026
Record last verified: 2026-01