AuthorisedTherapeutic exploratory (Phase II)Interventional

EORTC-2456-LCG-BTG: A randomized phase II study evaluating upfront SRT to all brain metastases followed by ivonescimab plus chemotherapy versus upfront ivonescimab plus chemotherapy in patients with asymptomatic active brain metastases from NSCLC.

When non-small cell lung cancer spreads to the brain, doctors want to know the best timing for different treatments. Sometimes brain spots are found on routine scans before they cause symptoms like headaches or dizziness. This Phase II trial is studying adults with lung cancer who have brain spots that are not currently causing symptoms. Participants are placed into one of two groups by chance. One group receives stereotactic radiotherapy (precise, targeted radiation) to the brain spots first, followed by chemotherapy and a new cancer drug called ivonescimab. The other group starts chemotherapy and ivonescimab straight away, without immediate brain radiation. Ivonescimab works by helping the immune system fight cancer and blocking the blood supply tumours need to grow. The main goal is to find out which approach keeps the brain free from cancer growth for longer.

At a glance

Status

Authorised

Phase

Therapeutic exploratory (Phase II)

Sponsor

European Organisation For Research And Treatment Of Cancer

Enrolment target

Start

19 Oct 2026

Non-small cell lung cancer

What is this study about?

Non-small cell lung cancer can sometimes spread to other organs, including the brain. These secondary growths are called brain metastases. Thanks to modern brain scans, doctors often find these small spots early, before they cause noticeable problems such as headaches, weakness, or confusion. When these spots cause no symptoms, doctors must decide whether to treat the brain immediately with radiation or start with whole-body drug treatments.

This trial investigates a specialised treatment called stereotactic radiotherapy (SRT). SRT delivers high doses of radiation directly to brain tumours with pinpoint accuracy, protecting the surrounding healthy brain tissue. The study also uses standard chemotherapy alongside an investigational drug called ivonescimab. Ivonescimab is a dual-action medicine designed to boost the body's immune system against cancer while also cutting off the blood vessels that feed tumour growth.

In this study, researchers are comparing two treatment pathways. Half of the patients receive pinpoint radiotherapy to their brain spots first, followed by ivonescimab and chemotherapy. The other half start ivonescimab and chemotherapy right away, saving radiotherapy for later if the brain spots begin to grow.

By comparing these two groups, researchers hope to discover which approach keeps brain tumours under control for longer, delays the need for further brain treatments, and offers patients the best possible quality of life.

Key takeaways

The trial tests whether targeted brain radiation before drug treatment works better than starting drugs right away.
It is for adults with non-small cell lung cancer and brain spots that do not cause symptoms.
Drug treatment includes standard chemotherapy combined with a new medicine called ivonescimab.
Participants have regular brain scans and check-ups to track their response and safety.
Taking part is voluntary, and you can withdraw at any point without losing standard NHS care.

Who may be eligible?

This trial is designed for adults aged 18 or over who have been diagnosed with non-small cell lung cancer that has spread to the brain. To take part, the spots in your brain must be 'asymptomatic'—meaning they were found on scans but are not currently causing symptoms like seizures, severe headaches, or limb weakness.

You will need to be well enough to carry out everyday activities and have blood tests showing that your kidneys, liver, and bone marrow are working safely.

You may not be eligible if your brain tumours are causing symptoms that require high-dose steroid treatment or immediate brain surgery, or if you have previously had radiation to these specific brain spots. Your hospital cancer team can look at your scan results and medical history to check if this study is suitable for you.

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 aged 18 or older.
I have been diagnosed with non-small cell lung cancer.
Scans show the cancer has spread to my brain.
I do not have symptoms from the brain spots (such as severe headaches, seizures, or confusion).
I am well enough to attend regular hospital appointments for infusions and scans.

Answer every question to see your result.

What does participation involve?

If you decide to join, you will be randomly assigned by a computer to one of two treatment groups. If you are in the first group, you will have pinpoint radiotherapy (SRT) over one or a few outpatient sessions, followed by regular infusions of ivonescimab and chemotherapy. If you are in the second group, you will start ivonescimab and chemotherapy infusions right away. Chemotherapy and ivonescimab are given through a drip into a vein, usually once every three weeks at the hospital. Throughout the trial, you will attend regular clinic visits for blood tests, physical checks, and brain MRI scans every few months to monitor your health and see how the tumours are responding. You can expect to stay on study treatment for as long as it helps you and the side effects remain manageable.

Potential risks and benefits

Taking part may help keep your cancer under control, and you will be monitored very closely by a specialist hospital team. The findings could also help future patients with lung cancer. However, there is no guarantee this treatment will work better than standard care. You may experience side effects from chemotherapy (such as tiredness, nausea, hair thinning, or increased risk of infection), radiotherapy (such as fatigue, headaches, or rarely, swelling in brain tissue), or ivonescimab (such as immune-related inflammation). You are free to leave the trial at any time without giving a reason, and your regular NHS medical care will not be 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
Netherlands

Common questions

What does 'asymptomatic brain metastases' mean?

It means cancer has spread to the brain, but the tumours are small or located where they do not cause problems like headaches, dizziness, or seizures.

Can I choose which treatment group I join?

No. A computer randomly selects your group to make sure the trial is fair and the results are scientifically reliable.

What is stereotactic radiotherapy (SRT)?

SRT is a non-surgical treatment that focuses precise beams of radiation directly at brain tumours, causing minimal damage to healthy surrounding brain tissue.

How is ivonescimab given?

Ivonescimab is given as an intravenous infusion (a drip into a vein) at the hospital alongside standard chemotherapy.

Will taking part cost me anything?

The trial drugs and study-related tests are provided free of charge, although you may need to travel to the hospital more frequently for scans and check-ups.