CompletedPhase IIIInterventional

A randomized, open-label phase 3 study of amivantamab + FOLFIRI versus cetuximab/bevacizumab + FOLFIRI in participants with KRAS/NRAS and BRAF wildtype recurrent, unresectable or metastatic colorectal cancer who have received prior chemotherapy

This phase 3 trial is studying a new treatment for adults with advanced bowel (colorectal) cancer that has spread or cannot be removed by surgery. It is designed for people whose cancer has started growing again after their first round of chemotherapy. The trial focuses on people whose tumours have normal (unmutated or 'wild-type') KRAS, NRAS, and BRAF genes. Participants are randomly put into one of two groups. One group receives a new targeted medicine called amivantamab (given as an injection under the skin) along with standard FOLFIRI chemotherapy. The other group receives standard targeted drugs (cetuximab or bevacizumab) plus FOLFIRI chemotherapy through a drip. The main goal is to find out if amivantamab helps patients live longer without their cancer worsening compared to existing treatments. The trial drug and extra tests are free, and travel costs are reimbursed.

At a glance

Status

Completed

Phase

Phase III

Sponsor

Janssen-Cilag International NV

Enrolment target

700

Start

26 Nov 2024

Estimated completion

13 Oct 2026

Recurrent, unresectable or metastatic colorectal cancer

What is this study about?

Bowel cancer, also called colorectal cancer, affects the large bowel or rectum. In some cases, cancer cells spread to other organs or return after initial treatment. When surgery cannot remove the cancer, doctors often rely on chemotherapy alongside targeted medicines. Targeted medicines are designed to find and block specific proteins that cancer cells need to survive and multiply. Over time, however, bowel cancer can become resistant to these treatments, which is why researchers are searching for new, more effective options.

This trial focuses on people with a specific genetic profile known as 'wild-type' bowel cancer. This simply means that certain genes in the cancer cells—called KRAS, NRAS, and BRAF—do not carry specific mutations. Knowing this genetic profile helps doctors choose treatments that have the highest chance of working.

The study tests a new targeted drug called amivantamab. Amivantamab is designed to attach to two different growth signals on cancer cells and switch them off, which may slow down or stop the tumour from growing. Researchers are comparing amivantamab given with chemotherapy against standard targeted treatments (cetuximab or bevacizumab) given with the same chemotherapy. This will help doctors learn whether amivantamab can offer patients longer disease control and a better quality of life.

Key takeaways

Compares a new targeted drug (amivantamab) to standard targeted therapies alongside chemotherapy.
Aimed at adults with advanced bowel cancer that has grown after one line of chemotherapy.
Requires your tumour to have normal (wild-type) KRAS, NRAS, and BRAF genes.
Participants are assigned to a treatment group by chance (randomisation).
All trial medicines and tests are provided for free, and travel costs are reimbursed.

Who may be eligible?

This trial is for adults aged 18 and older who have bowel cancer that has spread to other parts of the body (metastatic) or cannot be removed with surgery. To qualify, you must have already had one prior course of chemotherapy for your advanced bowel cancer, and scans must show that the cancer has started growing or returned since that treatment.

Your tumour must also be confirmed as 'wild-type' for KRAS, NRAS, and BRAF genes through genetic testing of a tumour sample. In addition, you need to be in reasonably good general health—able to walk around and carry out light daily tasks—and have adequate kidney, liver, and bone marrow function based on routine blood tests.

You cannot join the trial if you are pregnant or breastfeeding. Both men and women taking part must agree to use effective contraception during the study and for six months after treatment ends to avoid potential harm to an unborn baby.

Could this study suit you?

Answer these quick questions to see if you may be eligible. This is a guide only — the research team makes the final call.

You are aged 18 or older.
You have advanced bowel cancer that cannot be removed by surgery.
Your cancer has grown or returned after your first chemotherapy treatment.
Your tumour has tested negative for KRAS, NRAS, and BRAF mutations (wild-type).
You are well enough to carry out everyday activities.
You agree to use reliable contraception during and shortly after the trial.

Answer every question to see your result.

What does participation involve?

Taking part starts with a screening period of up to 28 days to check your general health through blood tests, scans, and physical examinations. If you are eligible, a computer will assign you by chance to one of two treatment groups. One group receives amivantamab as an injection under the skin plus FOLFIRI chemotherapy through a drip into a vein. The other group receives either cetuximab or bevacizumab plus FOLFIRI chemotherapy through a drip.

You will attend regular hospital appointments for your treatments, blood tests, and health questionnaires. CT or MRI scans will be carried out periodically to see how your tumour is responding. You will continue treatment as long as it is helping you and side effects remain manageable. After finishing treatment, the study team will keep in touch to check on your health. The total study runs for around 2 years and 9 months, and reasonable travel and parking costs will be paid back to you.

Potential risks and benefits

Taking part may help control your bowel cancer and could help future patients by improving medical knowledge, but direct health benefits cannot be guaranteed. Like all cancer treatments, the medicines in this trial can cause side effects. Common risks include skin rashes, tiredness, diarrhoea, feeling sick, reduced blood cell counts, and mild allergic reactions during or after the injections. Less common but serious risks include lung inflammation or heart complications. Your medical team will monitor you closely at every visit to manage any symptoms quickly. Taking part is completely your choice, and you can withdraw from the study at any time without it affecting your standard NHS care.

Locations (7)

St. Bartholomews Hospital
City only
London, England
University College Hospital
Approximate
London, England
Castle Hill Hospital
Approximate
Cottingham, England
The Royal Marsden Hospital
Approximate
London, England
Mount Vernon Cancer Centre
City only
Northwood, England
Birmingham Heartlands Hospital
Unverified
Birmingham, England
St. James's University Hospital
Unverified
Leeds, England

Common questions

What does 'wild-type' mean?

It means your cancer cells have normal, unmutated versions of specific genes (KRAS, NRAS, and BRAF). Doctors test for this because it helps predict which targeted therapies are most likely to work.

Can I choose which treatment group I join?

No. A computer randomly decides whether you receive the new drug amivantamab or standard targeted treatment. This random selection is essential to make sure the study results are fair and accurate.

Will taking part in this trial cost me anything?

No. The trial medication, clinic visits, and all study-related tests are provided free of charge. The study sponsor will also reimburse reasonable travel and parking expenses.

How is the trial drug amivantamab given?

Amivantamab is given as a simple injection under the skin, whereas the chemotherapy and standard targeted medicines are given via a drip into a vein.

Can I leave the study if I change my mind?

Yes. You have the right to leave the trial at any point, for any reason. Your regular hospital team will continue to provide you with the best available standard treatment.

How to find out more

Study Team

Participate-In-This-Study@its.jnj.com - Official trial record

Always speak to your GP or specialist before deciding to take part in a study.