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

ConditionsAdvanced Microsatellite Stable Colorectal CarcinomaMetastatic Microsatellite Stable Colorectal CarcinomaStage III Colorectal Cancer AJCC v8Stage IV Colorectal Cancer AJCC v8
Trial statusNot yet recruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorCity of Hope Medical Center

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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)

Trial design

Design model

Sequential

Treatments tested in this trial

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

  • Computed Tomography

    Procedure/Surgery

    Undergo CT

  • Fluorouracil

    Drug

    Given IV

  • Irinotecan

    Drug

    Given IV

  • Ivonescimab

    Biological/Vaccine

    Given IV

  • Leucovorin Calcium

    Drug

    Given IV

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI

  • Muzastotug

    Biological/Vaccine

    Given IV

Treatment groups

30 Participants
are divided into 3 treatment groups
Group A: Arm A (muzastotug, ivonescimab)Experimental treatment 5 interventions
Group B: Arm B (muzastotug, ivonescimab, leucovorin, fluorouracil)Experimental treatment 7 interventions
Group C: Arm C (muzastotug, ivonescimab, FOLFIRI)Experimental treatment 8 interventions

Trial outcomes

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.

Time frame
Up to 6 weeks or 3 doses of ivonescimab, whichever is longer

Secondary outcomes

1

Treatment-related adverse event rates

Will be assessed by NCI CTCAE version 5.0, delineated by grade and attribution, 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.

Time frame
Up to 30 days after completion of study treatment
2

Objective response rate

Defined as rate of participants achieving confirmed complete response (CR) or partial response (PR), as assessed by the investigator using Response Evaluation Criteria in Solid Tumors 1.1. The point estimate and 95% confidence intervals will be provided using the Clopper-Pearson methods. Logistic regression modeling of responders (CR or PR) and non-responders will be used to estimate the level of association of treatment and objective response.

Time frame
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
3

Duration of response

Survival distributions will be estimated using the Kaplan-Meier (KM) method. Survival curves will be compared between groups using the log-rank test. Median and landmark time-point estimates will be based on the KM estimates. The average hazard ratios (HR) will be estimated using a Cox proportional-hazards model. An assessment of the proportional-hazards assumption will be performed, and an assessment of the time-dependent HR will be done.

Time frame
From the time when a response is experienced to progression or death, assessed up to 2 years after completion of study treatment
4

Progression-free survival

Survival distributions will be estimated using the KM method. Survival curves will be compared between groups using the log-rank test. Median and landmark time-point estimates will be based on the KM estimates. The average HR will be estimated using a Cox proportional-hazards model. An assessment of the proportional-hazards assumption will be performed, and an assessment of the time-dependent HR will be done.

Time frame
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

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

City of Hope Medical Center

Lead sponsor

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: