AuthorisedTherapeutic confirmatory (Phase III)Interventional

A Randomized, Open-label, Phase 3 Trial of Petosemtamab in Combination With mFOLFOX6 or FOLFIRI Versus Cetuximab in Combination With mFOLFOX6 or FOLFIRI as First-line Treatment for Participants With RAS and BRAF Wild-type, Unresectable or Metastatic, Left-sided Colorectal Cancer.

This clinical trial is looking at a new treatment combination for people newly diagnosed with advanced bowel (colorectal) cancer. It focuses on cancer that started on the left side of the large bowel, has spread or cannot be removed by surgery, and does not have mutations in the RAS or BRAF genes. Participants will receive standard chemotherapy (either mFOLFOX6 or FOLFIRI) along with one of two targeted drugs: the new drug petosemtamab, or the current standard drug cetuximab. Targeted drugs work by finding and attacking specific parts of cancer cells. The main aim of the study is to see if petosemtamab keeps the cancer from growing for longer and shrinks tumours more effectively than cetuximab. Doctors will also track side effects and ask participants about their daily wellbeing and quality of life.

At a glance

Status

Authorised

Phase

Therapeutic confirmatory (Phase III)

Sponsor

Genmab A/S

Enrolment target

Start

19 Oct 2026

Colorectal Cancer

What is this study about?

Bowel cancer, also called colorectal cancer, starts in the large intestine. When the cancer cannot be removed by surgery or has spread to other organs (known as metastatic cancer), doctors usually recommend drug treatments to control it. The position where the tumour first started can change how it behaves. Cancers that start on the left side of the bowel often respond particularly well to certain targeted medicines, as long as the tumour cells do not carry specific gene changes called RAS or BRAF mutations.

Currently, the standard first treatment for this type of bowel cancer is chemotherapy combined with a targeted drug called cetuximab. While this treatment can work well, doctors are looking for ways to control the cancer for longer and help people live better, fuller lives. This trial investigates a new targeted drug called petosemtamab to see if it works better than cetuximab.

Petosemtamab is designed to attach to two different proteins found on cancer cells, aiming to block cancer growth and help the body's immune system fight the tumour. By comparing petosemtamab directly against cetuximab—with both given alongside standard chemotherapy—researchers hope to find out if this new medicine provides a more powerful first-line treatment for patients.

Key takeaways

A phase 3 trial comparing a new targeted medicine (petosemtamab) with standard targeted therapy (cetuximab).
All participants receive standard chemotherapy alongside their targeted drug; no one receives a placebo.
Open to adults with newly diagnosed, advanced bowel cancer that started on the left side.
Tumours must be tested to confirm they do not have RAS or BRAF gene mutations.
Taking part involves regular hospital visits for drip infusions, blood tests, and scans.
Participation is entirely voluntary and you can stop at any time.

Who may be eligible?

This study is open to adults aged 18 and over who have been diagnosed with bowel cancer that started on the left side of the colon or rectum. To be suitable, the cancer must be advanced, meaning it cannot be completely removed with surgery or has spread to other parts of the body.

Your tumour will need to be tested for certain genetic markers. You can only join if your cancer is 'RAS and BRAF wild-type', which simply means the cancer cells do not have specific faults or mutations in the RAS and BRAF genes. In addition, you must not have had any previous systemic treatment (such as chemotherapy) for this advanced stage of cancer.

Because every person's health is different, the trial doctors will also check your overall fitness, blood test results, and organ function to make sure it is safe for you to take part.

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.

I am 18 years of age or older.
I have been diagnosed with advanced bowel cancer that cannot be removed by surgery or has spread.
My cancer started on the left side of my bowel (colon or rectum).
I have not yet started chemotherapy or drug treatment for this advanced stage of cancer.
My doctor has confirmed (or can test) that my tumour is RAS and BRAF wild-type.

Answer every question to see your result.

What does participation involve?

Taking part in this study means visiting a hospital clinic regularly for treatment and monitoring. Because it is a randomised trial, a computer will assign you by chance to receive either petosemtamab plus chemotherapy, or cetuximab plus chemotherapy. Both groups receive active, proven chemotherapy.

All treatments are given directly into a vein through a drip (intravenous infusion). During your hospital visits, you will have regular safety checks, including blood tests, physical examinations, and heart checks. You will also have regular imaging scans, such as CT or MRI scans, to see how the tumour is responding to the medicine.

You will be asked to fill in short questionnaires about how you are feeling and any symptoms or side effects you notice. Treatment usually continues for as long as it is helping to keep your cancer under control and you are not troubled by difficult side effects. After finishing treatment, the medical team will keep in touch to monitor your health.

Potential risks and benefits

The possible benefit of taking part is that the new drug combination may help shrink your tumour or keep it stable for longer than standard treatment, though this cannot be guaranteed. You will also receive very close medical care and frequent check-ups. However, all cancer treatments carry a risk of side effects. Both the chemotherapy and targeted medicines can cause problems such as skin rashes, tiredness, nausea, diarrhoea, or a drop in blood cell counts. There is also a chance the new treatment causes unexpected side effects. Taking part is completely your choice, and you can change your mind and leave the trial at any time without your regular NHS care being affected.

Locations (1)

Some site locations are approximate. We're improving this — please verify with the trial team before travelling.

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Unverified
Spain

Common questions

What does 'open-label' and 'randomised' mean?

Randomised means a computer places you into a treatment group by chance, like flipping a coin. Open-label means both you and your doctor will know which treatment you are receiving.

What does 'RAS and BRAF wild-type' mean?

'Wild-type' is a medical term meaning normal or unchanged. It means your tumour does not have specific faults in the RAS or BRAF genes, making it more likely to respond to these targeted drugs.

Will I receive a placebo (dummy medicine)?

No. There is no dummy pill or placebo in this trial. Everyone who takes part receives active standard chemotherapy combined with an active targeted drug.

How long will I be in the trial?

You can usually stay on the trial treatment for as long as it continues to control the cancer and any side effects remain manageable. The medical team will follow your progress over several months or years.

Do I have to pay to take part?

No, you do not have to pay for the trial treatments or the extra tests. In many cases, help with travel expenses to hospital visits may also be available.