Active not recruitingPHASE2INTERVENTIONAL

A Study of Encorafenib Plus Cetuximab Taken Together With Pembrolizumab Compared to Pembrolizumab Alone in People With Previously Untreated Metastatic Colorectal Cancer

This study is for people with advanced bowel cancer that has spread to other parts of the body (metastatic colorectal cancer). The cancer must have certain genetic features: it needs to show a tendency to mutate quickly (called 'genetic hypermutability' or 'dMMR') and have an abnormal gene called 'BRAF'. Participants should not have received any previous treatment for their advanced cancer. The study aims to find out if giving three medicines together (encorafenib, cetuximab, and pembrolizumab) works better than giving pembrolizumab alone. Pembrolizumab is given as a drip into a vein at the clinic. Half the participants will also take encorafenib as a tablet at home and receive cetuximab as a drip at the clinic. Researchers will closely monitor all participants.

At a glance

Status

Active not recruiting

Phase

PHASE2

Sponsor

Pfizer

Enrolment target

107

Start

11 Jul 2022

Estimated completion

26 Jan 2027

Metastatic Colorectal Cancer

What is this study about?

This research study is looking into new ways to treat advanced bowel cancer (metastatic colorectal cancer). 'Metastatic' means the cancer has spread from where it started to other parts of your body. Doctors are particularly interested in bowel cancers that have two specific features: they have a gene fault called 'BRAF', and they also show a high number of genetic changes, sometimes called 'genetic hypermutability' or 'dMMR'.

For patients who haven't had treatment for their advanced cancer yet, this study wants to see how well a combination of three medicines works. These medicines are called encorafenib, cetuximab, and pembrolizumab. Scientists believe that by combining these powerful cancer drugs, they might be able to create a more effective treatment than using pembrolizumab on its own.

The main goal is to understand the effects of these medicines, especially how safe and effective the three-drug combination is. This kind of research helps doctors find better treatments for bowel cancer in the future and offers new options for patients with these specific types of cancer.

Key takeaways

This study is for advanced bowel cancer that has spread (metastatic).
It focuses on cancers with a specific gene change (BRAF V600E) and a high number of genetic changes (dMMR/MSI-H).
It compares a new combination of three drugs with pembrolizumab alone.
Participants must not have had previous treatment for their advanced cancer.
All participants receive pembrolizumab by drip; some also get encorafenib (tablet) and cetuximab (drip).

Who may be eligible?

To join this study, you would need to have bowel cancer that has spread (stage IV). Your cancer cells must also show a 'BRAF V600E' gene change and a high tendency for genetic changes (called MSI-H or dMMR). It's important that you haven't had any other treatments for this advanced cancer yet. You also need to be generally well enough to take part, as assessed by your doctor, and your body organs should be working properly. The study is open to both men and women, aged 16 or older.

There are also some reasons why you might not be able to join. For example, if your bowel cancer has a different type of gene change called 'RAS mutant', or if doctors don't know your RAS status, you wouldn't be eligible. You also can't have active cancer that has spread to your brain or the fluid around it. If you have certain other serious health problems, such as some heart conditions, or if you've recently had specific vaccines, you might not be able to participate. Also, if you've previously taken similar types of cancer drugs (like certain BRAF inhibitors, EGFR inhibitors, or immune checkpoint inhibitors), you wouldn't be able to join this study.

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.

Do I have bowel cancer that has spread to other parts of my body?
Has my cancer been tested and confirmed to have the 'BRAF V600E' gene change?
Has my cancer been tested and confirmed to have many genetic changes (MSI-H/dMMR)?
Have I received any other treatments for my advanced bowel cancer yet?
Am I generally well enough to take part in a study, as my doctor would assess?

Answer every question to see your result.

What does participation involve?

If you join this study, you will receive pembrolizumab as a drip directly into a vein (this is called an IV infusion) at the study clinic. This will happen regularly. You will be assigned to one of two groups: either you will receive pembrolizumab alone, or you will receive pembrolizumab along with two other medicines. If you are in the second group, you will take encorafenib as a tablet by mouth at home every day, and you will also receive cetuximab as an IV infusion at the study clinic.

Throughout the study, you will have regular visits to the clinic so the study team can check how you are doing, monitor any side effects, and make sure the treatment is working. These visits will involve various tests and assessments, which your study team will explain in detail. The total duration of your participation will depend on how you respond to the treatment and the study plan, which your doctor will discuss with you.

Potential risks and benefits

Taking part in a clinical trial like this could offer potential benefits, such as receiving new treatments for your cancer before they are widely available. However, there are also potential risks, as the effects of these new combinations are still being studied, and you might experience side effects. Your care team will explain all known side effects and monitor you closely. It's important to remember that you are free to leave the study at any time, for any reason, without it affecting your usual medical care.

Locations (59)

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

Mayo Clinic Building - Phoenix
Verified postcode
Phoenix, United States
Mayo Clinic Hospital
Verified postcode
Phoenix, United States
Mayo Clinic
Verified postcode
Scottsdale, United States
Mount Sinai Cancer Center
Verified postcode
Miami Beach, United States
The West Clinic, PLLC dba West Cancer Center
Verified postcode
Germantown, United States
MD Anderson Cancer Center
Verified postcode
Houston, United States
Austin Health
Verified postcode
Heidelberg, Australia
Peter MacCallum Cancer Centre
Verified postcode
Melbourne, Australia
Royal Melbourne Hospital
Verified postcode
Parkville, Australia
Imelda General Hospital
Verified postcode
Bonheiden, Belgium
Institut Jules Bordet
Verified postcode
Anderlecht, Belgium
Cliniques universitaires Saint-Luc
Verified postcode
Brussels, Belgium

Common questions

What is 'metastatic colorectal cancer'?

This means bowel cancer that has spread from where it started to other parts of your body, like the liver or lungs.

What does 'BRAF gene' mean?

BRAF is a gene, and sometimes it can have a change or 'mutation' (like BRAF V600E) that makes cancer cells grow. This study is for cancers with this specific change.

What is 'dMMR' or 'genetic hypermutability'?

This describes cancer cells that have a problem repairing their DNA, which leads to many genetic changes. This can sometimes make them respond better to certain treatments.

What are the medicines used in this study?

The medicines are encorafenib (a tablet), cetuximab (given by drip), and pembrolizumab (given by drip). Some people will get all three, others just pembrolizumab.

Will I know if I'm getting the new combination or just pembrolizumab?

The study design means some participants will receive the triple combination and others will receive pembrolizumab alone. Your study doctor will explain which group you are in.