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A Study of Ivonescimab Combined with Fluorouracil, Folinic Acid, and Oxaliplatin Compared to Bevacizumab for Patients with Metastatic Colorectal Cancer

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What is this trial about?

A plain-language summary of the goals, design and what participants do

This study involves people with metastatic colorectal cancer, which is cancer that started in the colon or rectum and has spread to other parts of the body. The study will test a treatment that combines ivonescimab, an experimental medication also known by the code names AK112 or SMT112, with a chemotherapy regimen called FOLFOX. FOLFOX consists of three medications: fluorouracil, oxaliplatin, and folinic acid. This combination will be compared to another treatment that uses bevacizumab combined with the same FOLFOX chemotherapy. The purpose of the study is to compare how long patients live without their cancer getting worse when treated with ivonescimab plus FOLFOX compared to bevacizumab plus FOLFOX.

Participants in this study will be randomly assigned to receive either ivonescimab or bevacizumab, both given in combination with FOLFOX chemotherapy. The study is designed so that neither the participants nor their doctors will know which treatment is being given, which helps ensure fair comparison of the results. The medications will be given through a vein, which means they are delivered directly into the bloodstream through an intravenous line. During the study, participants will have regular check-ups where doctors will monitor the size of tumors using imaging scans and assess how well the treatment is working. The study will also track any side effects that occur and measure the levels of ivonescimab in the blood at different times.

The study will also collect information about how long participants live overall, how many people respond to treatment, and how long those responses last. Doctors will monitor for any unwanted effects from the medications and check blood tests for abnormal results. For those receiving ivonescimab, the study will also check whether the body develops antibodies against this medication, which could affect how well it works. This study is intended for people who have not yet received treatment for their metastatic colorectal cancer, though previous treatment for earlier stages of the disease is allowed if it was completed more than twelve months before the cancer spread.

The research process

The trial runs in 6 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Treatment assignment

    Upon joining the study, you will be randomly assigned to one of two treatment groups. This process is called randomization and ensures fairness in the study.

    The study is double-blind, which means neither you nor your doctor will know which specific treatment group you are in during the trial.

  2. Step 2

    Treatment administration

    You will receive a combination of medications administered through a vein (intravenous infusion or injection).

    The treatment consists of either ivonescimab or bevacizumab combined with a chemotherapy regimen called mFOLFOX6.

    The mFOLFOX6 regimen includes three medications: oxaliplatin, folinic acid (also known as leucovorin), and fluorouracil (also known as 5-FU).

    All medications will be given directly into your bloodstream through intravenous administration.

  3. Step 3

    Regular tumor assessments

    Throughout the study, your tumors will be measured regularly using imaging scans.

    These measurements will be reviewed by an independent committee of radiologists who are not involved in your direct care.

    The assessments follow standardized criteria called RECIST v1.1, which is a system used to evaluate whether tumors are growing, shrinking, or staying the same size.

    These scans will help determine if the treatment is working for you.

  4. Step 4

    Safety monitoring

    Your health will be closely monitored throughout the study period.

    This includes regular laboratory tests to check your blood and organ function.

    Any side effects or health changes you experience will be recorded and assessed for their severity.

    Blood samples will be taken at specific times to measure the levels of medication in your bloodstream.

  5. Step 5

    Immunogenicity testing

    Blood samples will be collected to check if your body develops antibodies against the study medication.

    Antibodies are proteins your immune system might produce in response to the medication.

    This testing helps understand how your body responds to the treatment over time.

  6. Step 6

    Ongoing treatment period

    You will continue receiving treatment as long as your disease does not progress and you do not experience unacceptable side effects.

    The study is expected to continue until July 2028.

    Your participation duration will depend on how your disease responds to treatment and your overall health condition.

Who can join the trial?

6 criteria

  • You must have metastatic colorectal cancer, which means cancer that started in the colon or rectum and has spread to other parts of the body, and it cannot be removed completely with surgery.
  • Your cancer must be confirmed by examining tissue or cells under a microscope, which is called histological or cytological confirmation.
  • You must have an ECOG performance status score of 0 or 1. This is a scale that measures how well you can perform daily activities, where 0 means you are fully active and 1 means you have some restrictions but can still do light work.
  • You must not have received any previous treatment with medications given through the bloodstream for your metastatic colorectal cancer. If you received such treatment for early-stage disease, more than 12 months must have passed since you finished that treatment before your cancer came back or spread.
  • You must have at least one tumor that can be measured accurately and repeatedly using imaging scans, according to specific measurement rules called RECIST v1.1. Tumors in the brain and tumors that were previously treated with radiation cannot be used for measurement unless they have grown after the radiation treatment.
  • Your tumor must be tested to determine the mutation status of certain genes called BRAF, KRAS, and NRAS. This means doctors need to know if there are specific changes in these genes in your cancer cells, either from previous test results or by testing your tumor tissue.

Who cannot join the trial?

6 criteria

  • If a certified lab test has shown that your tumor has MSI‑H/dMMR (a genetic change that makes the cancer behave differently), you cannot join the study.
  • If you have a BRAF V600E mutation (a specific gene change) or a DPD deficiency (a condition that can cause problems with certain chemotherapy drugs), you are excluded.
  • If you have already received immunotherapy (treatments that use your immune system) or anti‑angiogenic therapy (drugs that block blood vessels feeding the tumor), including immune checkpoint inhibitors, immune checkpoint agonists, or immune cell therapy, you cannot participate.
  • If cancer has spread to your central nervous system (CNS) (brain or spinal cord) and is causing symptoms—especially if the spots are 1.5 cm or larger, have bleeding (hemorrhagic), you had brain radiation within the last 7 days, may need radiation soon, or you have leptomeningeal disease (cancer in the thin membranes around the brain and spinal cord)—you are excluded.
  • If you have only a few spread sites (oligometastatic disease) that can be completely removed by surgery according to a team’s plan (resectable with a multidisciplinary plan), you cannot join.
  • If you have fluid buildup in the abdomen (ascites) that required a draining procedure (paracentesis) within the past 30 days, you are not eligible.
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Investigated drugs

  • Ivonescimab

    is an investigational medication being studied in this trial. It is given in combination with chemotherapy drugs to treat metastatic colorectal cancer, which is cancer that has spread to other parts of the body. This medication is being tested to see if it can help slow down or stop the growth of cancer cells.

  • Bevacizumab

    is a medication that is already approved and used to treat various types of cancer, including colorectal cancer. It works by blocking the growth of new blood vessels that tumors need to grow. In this study, it is being used as a comparison treatment to see how well the investigational medication works.

  • FOLFOX

    is a combination of chemotherapy drugs that includes fluorouracil (also called 5-FU), oxaliplatin, and leucovorin. This chemotherapy combination is commonly used to treat colorectal cancer. The drugs work together to kill cancer cells or stop them from growing. Both groups in this study will receive this chemotherapy combination along with either the investigational medication or the comparison medication.

What is already known about the treatment

  • Ivonescimab

    Ivonescimab is an investigational medication currently being studied in clinical trials for the treatment of metastatic colorectal cancer, which means cancer that has spread from the colon or rectum to other parts of the body. It is given in combination with a chemotherapy regimen called mFOLFOX6, which includes the drugs fluorouracil, oxaliplatin, and leucovorin, and is administered intravenously through a vein. The medication works at the molecular level by targeting specific proteins on cancer cells and immune cells to help the body's immune system recognize and attack the cancer while also blocking signals that help tumors grow new blood vessels. Ivonescimab belongs to a class of drugs known as immunotherapy agents combined with anti-angiogenic properties, designed to both stimulate the immune response against cancer and prevent tumor blood vessel formation.

  • Bevacizumab

    Bevacizumab is an approved medication widely used in cancer treatment, including metastatic colorectal cancer, and is administered intravenously through a vein in combination with chemotherapy regimens such as mFOLFOX6. It works by blocking a protein called vascular endothelial growth factor (VEGF), which tumors use to create new blood vessels that supply them with nutrients and oxygen needed for growth and spread. By preventing the formation of these new blood vessels, bevacizumab helps slow down or stop tumor growth and is classified as an anti-angiogenic or targeted therapy medication. This medication has been established in medical practice for many years and serves as a standard treatment option for patients with advanced colorectal cancer.

Investigated diseases

Metastatic Colorectal Cancer – Metastatic colorectal cancer is an advanced stage of cancer that begins in the colon or rectum and has spread to distant parts of the body. The disease develops when abnormal cells in the large intestine grow uncontrollably and form tumors. As the cancer progresses, these cells break away from the original tumor and travel through the bloodstream or lymphatic system to other organs. The most common sites where colorectal cancer spreads include the liver, lungs, and distant lymph nodes. In the metastatic stage, the cancer has moved beyond the bowel wall and nearby tissues to affect organs in other parts of the body. This spread of cancer cells significantly changes how the disease behaves and affects the body's normal functions.
Trial detailsLast updated 2 Oct 2026
Age18+ yearsPhasePhase IIITrial ID2025-521587-35-00Protocol codeSMT112-3005Estimated enrolment600 patientsSponsorSummit Therapeutics Inc.

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On this site, “treatment” means an investigational medicine being studied in a clinical trial. Its safety and efficacy for the use being studied have not yet been confirmed, some participants may receive a placebo or a comparator medicine, and taking part does not guarantee any health benefit. The decision to take part is made by the doctor at the research site. This site is for information only and does not replace medical advice.

This service is not affiliated with the European Commission, the EMA, or the official CTIS system. Most information comes from publicly available international clinical-trial registries, supplemented by data from academic sites, national regulators and commercial sponsors. On this site, “treatment” and “therapy” mean a medicine being tested in a clinical trial. Its safety and effectiveness in the use being studied are not yet confirmed, some participants may receive a placebo or a comparator, and taking part does not guarantee a health benefit. The doctor at the research site decides who can take part. This site provides information, not medical advice. Certain content and visual elements on this website have been generated or enhanced using artificial intelligence (AI).