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Study of ONO-4578 and nivolumab with drug combination for first-line treatment in patients with PD-L1 positive advanced colorectal cancer

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What is this trial about?

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

This clinical trial focuses on patients with PD-L1 positive advanced colorectal cancer. The study evaluates a new combination treatment approach that includes several medications: ONO-4578 (taken as tablets), Opdivo (nivolumab), bevacizumab, and a chemotherapy combination called mFOLFOX6 which consists of oxaliplatin, fluorouracil, and leucovorin.

The purpose of this research is to determine if two different dose levels of ONO-4578 given together with Opdivo and standard treatment (mFOLFOX6 plus bevacizumab) are safe and effective compared to the usual standard treatment alone. The medications will be given in different ways - some as tablets taken by mouth and others through an intravenous infusion into a vein.

During the study, participants will be randomly assigned to receive either the new combination treatment or the standard treatment. The study team will monitor how well the treatment works and track any side effects that may occur. Participants will have regular check-ups, including physical examinations and various medical tests to evaluate their response to treatment and ensure their safety throughout the study period.

The research process

The trial runs in 4 steps – from screening to follow-up. Each step says what happens and what the team monitors.

Step 1
Initial treatment phase
You will receive a combination of medications through different methods of administration:
- ONO-4578 as film-coated tablets taken by mouth
- Opdivo (nivolumab) given through intravenous infusion
- mFOLFOX6 regimen consisting of:
• Calcium folinate through intravenous infusion
• Oxaliplatin through intravenous infusion
• Fluorouracil through intravenous infusion
- Bevacizumab given through intravenous infusion
Step 2
Regular assessments
Throughout the study, you will undergo regular evaluations including:
- Physical examinations
- Laboratory tests to check blood, chemistry, and urine values
- Heart monitoring through ECG (electrocardiogram)
- Imaging scans to measure tumor response
Step 3
Response monitoring
Your response to treatment will be evaluated through:
- Regular imaging scans to measure tumor size
- Assessment of any changes in your cancer
- Monitoring of side effects
Independent experts will review your imaging results to evaluate how the treatment is working
Step 4
Safety monitoring
Throughout the study, you will be monitored for:
- Side effects and serious health events
- Any needed adjustments to medication doses
- Changes in laboratory test results
Your doctor may adjust or stop treatment based on how your body responds

Who can join the trial?

14 criteria

Age 18 years or older
Must be able and willing to provide informed consent and follow all study requirements
Diagnosed with advanced colorectal cancer that cannot be treated with surgery
Must have ECOG Performance Status of 0-1 (meaning able to carry out light daily activities with minimal or no assistance)
Must have test results available showing:
- Microsatellite stability or mismatch repair status
- BRAF mutation status in tumor
- PD-L1 positive status (Combined Positive Score of 1 or higher)
- No previous systemic treatment for advanced colorectal cancer
- Must have at least one measurable tumor that can be seen on imaging scans
- Must have adequate tumor tissue sample available for testing that has not been previously treated with radiation
- Must have adequate:
  - Bone marrow function
  - Kidney function
  - Liver function
  - Must agree to use effective birth control methods during the study (both male and female participants)

Who cannot join the trial?

14 criteria

Age below 18 years or above 75 years
History of autoimmune diseases (conditions where the body's immune system attacks healthy cells)
Previous treatment with immunotherapy (medications that help your immune system fight cancer)
Active or untreated brain metastases (cancer that has spread to the brain)
Significant heart conditions including uncontrolled hypertension (high blood pressure)
Active infections requiring systemic treatment (medications that affect the whole body)
Known HIV, hepatitis B, or hepatitis C infection
Other active cancers requiring treatment
Pregnancy or breastfeeding
Severe kidney or liver problems
Known allergies to study medications
Participation in other clinical trials within the past 30 days
Mental conditions that could interfere with study compliance
Any condition that, in the investigator's opinion, makes the patient unsuitable for the study

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Verified sites

All sites with verified contact details – recruitment status may not be available; ask directly

Verified
ASST Grande Ospedale Metropolitano Niguarda
Milan, Italy
Responsive
Istituto Europeo Di Oncologia S.r.l.
Milan, Italy
Responsive
Istituto Oncologico Veneto
Padua, Italy

Trial locations

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Investigated drugs

ONO-4578
is an investigational medication being studied for the treatment of colorectal cancer. It is being tested in combination with other medications as a first-line treatment for specific types of advanced colorectal cancer.
Opdivo
(nivolumab) is an immunotherapy medication that helps the body's immune system attack cancer cells. It works by blocking a protein that prevents the immune system from attacking cancer cells.
mFOLFOX6
is a combination chemotherapy regimen that includes several medications working together to fight cancer cells. It is commonly used as a standard treatment for colorectal cancer.
Bevacizumab
is a targeted therapy that works by blocking the formation of new blood vessels that feed tumors. This helps prevent tumor growth by cutting off their blood supply.

What is already known about the treatment

ONO-4578
An investigational drug being studied in combination with Opdivo (nivolumab) and standard chemotherapy for the treatment of PD-L1 positive advanced colorectal cancer. The medication is currently in Phase 2 clinical trials to evaluate its safety and efficacy at different dose levels. It is being tested as a first-line treatment option in combination with mFOLFOX6 and bevacizumab for patients with non-MSI-H/dMMR colorectal cancer.
Opdivo
A prescription immunotherapy medication administered via intravenous infusion that works by helping the immune system fight cancer cells. It belongs to a class of drugs called PD-1 inhibitors and is approved for treating various types of cancer, including specific cases of colorectal cancer. The medication works by blocking the PD-1 pathway, which helps activate T-cells to detect and destroy cancer cells more effectively.
Bevacizumab
An intravenous medication that belongs to a class of drugs called angiogenesis inhibitors, which work by blocking the formation of new blood vessels that feed tumors. It is commonly used in combination with chemotherapy for treating various types of cancer, including colorectal cancer, by preventing tumor growth and spread through its anti-angiogenic mechanism of action.
mFOLFOX6
A combination chemotherapy regimen that includes multiple drugs (fluorouracil, leucovorin, and oxaliplatin) administered intravenously to treat colorectal cancer. This standard-of-care treatment works by interfering with cancer cell division and growth through various mechanisms, including DNA damage and synthesis disruption, making it an established first-line therapy option for advanced colorectal cancer.

Investigated diseases

PD-L1 Positive Advanced Colorectal Cancer - A type of bowel cancer that has spread beyond its original location and shows specific protein markers called PD-L1 on the surface of cancer cells. The disease begins in the large intestine (colon) or rectum and develops from small growths called polyps that become cancerous over time. As it advances, the cancer grows through the layers of the intestinal wall and can spread to nearby lymph nodes and other organs. The presence of PD-L1 proteins on cancer cells makes this particular type distinct from other forms of colorectal cancer. The disease typically develops gradually, often starting with no symptoms and progressing to changes in bowel habits, abdominal discomfort, and unexplained weight loss.