A trial of durvalumab, oleclumab and monalizumab for non small cell lung cancer (PACIFIC-9) (2024)

This trial is looking at adding oleclumab or monalizumab to durvalumab for non small cell lung cancer.

It is for people whose cancer:

• has spread into nearby tissues and it isn’t possible to remove with surgery (stage 3 lung cancer) and
• hasn’t got worse following chemoradiotherapy

Chemoradiotherapy is a combination of chemotherapy and radiotherapy. It is a standard treatment for non small cell lung cancer(NSCLC). After chemoradiotherapy you might have durvalumab.

Durvalumab is an immunotherapy. It works by stimulating the immune system to fight cancer. This can slow down or stop the growth of the cancer. It is a standard treatment for some people after chemoradiotherapy for NSCLC.

Oleclumab and monalizumab are also immunotherapies. They work in slightly different ways. They also help the immune systemto recognise and attack cancer cells.

Doctors are looking at ways to improve treatment for non small cell lung cancer after chemoradiotherapy. In this trial you have one of the following:

• durvalumab and oleclumab
• durvalumab and monalizumab
• durvalumab and a dummy drug (placebo )

The main aims of the trial are to:

• find out if adding oleclumab or monalizumab to durvalumab improves treatment
• learn more about the side effects
• look for substances called biomarkers
• find out how treatment affects quality of life

The following bullet points are a summary of the entry conditions for this trial. Talk to your doctor or the trial team if you are unsure about any of these. They will be able to advise you.

Who can take part

You may be able to join this trial if all of the following apply. You:

• have cancer that has grown into nearby tissues or lymph nodes and you can’t have surgery to remove it (stage 3 lung cancer)
• are having or have had chemotherapy and radiotherapy together (chemoradiotherapy)
• have had at least 2 cycles of chemoradiotherapy which included a platinum drug alongside certain other chemotherapy drugs. Your doctor will know this.
• have had a certain dose of radiotherapy using either intensity modulated radiotherapy (IMRT or 3D conformal radiotherapy) . You doctor will know this.
• had a PET-CT scan within 3 months of starting chemoradiotherapy
• have a sample of cancer tissue (biopsy) available for the trial team to do some tests on
• have cancer with certain gene changes (mutations) in the lung cancer cells. The trial team test for these.
• are active but might not be able to do heavy physical work (performance status 0 or 1)
• weigh at least 40kg
• have satisfactory blood test results
• are willing to use reliable contraception during the trial and for a period after
• are able to give informed consent
• are at least 18 years old

Who can’t take part

Cancer related
You cannot join this trial if any of these apply. You:

• have a mix of small cell and non small cell lung cancer
• are going to have surgery as part of your routine treatment. For example you have a Pancoast tumours.
• have cancer spread to the tissues around the brain (leptomeningeal carcinomatosis)
• have cancer that has grown into major blood arteries such as the artery that supplies the lung or the heart
• have cancer that has the gene changes (mutations ) EGFR or ALK. Your doctor will know this.
• had chemotherapy before radiotherapy rather than having them at the same time for stage 3 non small cell lung cancer
• have cancer that got worse during chemoradiotherapy that included a platinum drug
• have or are having treatment for stage 3 NSCLC that included an immunotherapy, an experimental drug, radiotherapy or a type of drug called a monoclonal antibody
• have had durvalumab, monalizumab, or oleclumab in the past
• took part in a trial looking at durvalumab, monalizumab, or oleclumab even if you didn’t have these treatments
• still have moderate to severe side effects from chemoradiotherapy
• have had previous treatment with some types of immunotherapy. You doctor will know which ones these are.
• have ongoing side effects from an immunotherapy that is caused by the immune system
• are taking part in another trial unless it doesn’t involve a treatment or you took part in a clinical trial in the last 3 months
• have had another cancer that has got worse or needed treatment in the past 5 years unless it has a low chance of coming back. You can join if it was successfully treated non melanoma skin cancer , very early melanoma skin cancer, carcinoma in situ or very early cancers that can be treated with the aim to cure.

Medical conditions
You cannot join this trial if any of these apply. You:

• have had a heart attack in the last 6 months or a significant heart problem that needs treatment. The trial team check if you have a heart condition before you join the trial.
• have had a stroke or mini stroke in the last 6 months
• have had a lung clot in the last 6 months or a clot somewhere else in the body in the last 3 months
• have an abnormal heart rhythm
• have high blood pressure that isn’t well controlled with medication
• have a bleeding problem
• have lung damage or inflammation of the lungs
• have an active hepatitis B infection, hepatitis C infection, HIV, active tuberculosis or any other serious infection that needs treatment
• have a serious long term problem with your digestive system or any condition that causes diarrhoea
• have an autoimmune disease . You can still take part if you have certain autoimmune diseases. Your doctor can tell you about this.
• have a problem with how your immune system works
• have had a bone marrow or stem cell transplant with someone else’s cells (allogeneic transplant )
• might need to have another treatment for cancer
• are having or have had treatment for non small cancer that includes radiotherapy, chemotherapy or monoclonal antibody or an experimental treatment
• have had an immunotherapy in the past
• have medication that damps down the immune system within 14 days of starting durvalumab. You can join if you had low dose steroids.
• have had major surgery or a bad injury within 4 weeks of starting trial treatment or you might need major surgery while you are having trial treatment
• have any other medical condition or mental health problem that the trial team think could affect you taking part

Other
You cannot join this trial if any of these apply. You:

• have had a live vaccination within 30 days of the starting trial treatment
• are allergic to durvalumab, oleclumab or monalizumab or anything they contain
• are pregnant or breastfeeding

This phase 3 trial is taking place worldwide. The team need 999 people to have treatment in the trial with 44 people from the UK.

It is a randomised trial. There are 3 treatment groups with about 333 people in each group. Neither you nor your doctor can choose which group you are in. Nor will you know which group you are in. Your doctor can find this out if necessary.

You have one of the following:

• durvalumab and oleclumab (group 1)
• durvalumab and monalizumab (group 2)
• durvalumab and a dummy drug (placebo ) (group 3)

You have all your treatment as a drip into a vein. It takes about an hour to have each drug.

You have treatment in cycles. Each 4 week period is a cycle of treatment . The first day of each treatment cycle is called day 1. For the first 2 months only, you have:

• durvalumab on day 1
• oleclumab, monalizumab or the dummy drug on day 15

After that you have all your treatment on day 1 of each treatment cycle. You have this once every 4 weeks for up to one year. This is for as long as it is working and the side effects aren’t too bad.

You stop treatment if your cancer gets worse. Your doctor will talk to you about other treatment options.

Samples for research
The trial team ask you to give some extra blood samples. Where possible you have these at the same time as your routine blood tests.

They might ask you to give an extra sample of tissue if your cancer gets worse.

The researchers plan to use the samples to:

• look at substances called biomarkers to help work out why treatment might work for some people and not for others
• look at genes in your cancer cells to learn more about NSCLC
• measure small amounts of cancer cells that may be in the bloodstream. This is called circulating tumour DNA or ctDNA.
• see what happens to trial treatments in the body

You can say no to giving the extra tissue sample if your cancer gets worse. It won’t affect you taking part in the rest of the trial.

Quality of life
The trial team ask you to fill out a questionnaire:

• before you start treatment
• at set times during treatment

You do this on a phone or an electronic device. The questionnaire asks about side effects and how you’ve been feeling. This is called a quality of life study.

You see the doctor and have tests before you can take part. These include:

• blood tests
• a physical examination
• heart trace (ECG )
• a check of your lungs (lung function tests )
• CT scan or MRI scan

You see the doctor before each treatment to see how you are and for blood tests.

At home the team ask you to check your levels of oxygen in the blood. They provide you with a small device to do this. They’ll let you know when and how often to do this.

Scans
You have a scan every:

• 8 weeks for 48 weeks and then
• every 3 months until year 5 and then
• every 6 months until year 6

You stop having these trial scans if your cancer gets worse. If this happens, you will also have one more scan a few months later. Your doctor can tell you more about this.

Follow up
After you finish treatment you see the doctor for a check up one month later. And then you see them:

• at month 2 and at
• month 3

The team then contact you every 2 months to see how you are getting on. They check if you have started another cancer treatment.

The trial team monitor you during treatment and afterwards. Contact your advice line or tell your doctor or nurse if any side effects are bad or not getting better.

The combination of durvalumab and monalizumab is a new treatment. The combination of durvalumab and oleclumab is also a new treatment. So there may be possible side effects we don’t know about yet.

Not many people have had oleclumab. The most common side effects of durvalumab and oleclumab we know about so far include:

• fatigue (tiredness)
• itchy skin or skin rash
• diarrhoea
• lack of energy

The most common side effects of oleclumab alone include:

• fatigue (tiredness)
• a drop in the number of red blood cells causing an increased risk of tiredness or shortness of breath (anaemia )
• feeling sick

Other possible side effects of oleclumab include:

• skin rash, fever and pain in joints
• an allergic reaction
• worsening of heart problems or blood clots in the legs
• a restriction of blood supply to the body if you have had drugs that stop the growth of blood vessels. Symptoms could include chest pain and tummy pain.
• cramps, aches, tingling and burning in the legs
• blood clots
• a reaction that can happen while you are having oleclumab. This is called an infusion reaction. Signs include a high temperature (fever), chills, shortness of breath, feeling sick (nausea) and changes in blood pressure.

The possible side effects of monalizumab we know about so far include:

• a reaction that can happen while you are having monalizumab. This is called an infusion reaction. Signs include a high temperature (fever), chills, shortness of breath, feeling sick (nausea) and changes in blood pressure.
• having a flu-like or allergic reaction soon after or within a few hours of treatment
• an inflammatory condition which can damage the kidneys, joints or blood vessels in the skin

Symptoms of an allergic reaction include flushing, skin rash, fever, chills or shortness of breath. Severe reactions can cause breathing problems, low blood pressure and heart problems. This needs urgent treatment.

The team keep a close eye on you during treatment and afterwards. They will treat any problems straight away.

We have more information about durvalumab and its side effects.

Your doctor will talk to you about all the possible side effects of treatment before you join the trial.

Belfast

Bristol

Dundee

Edinburgh

London

Middlesbrough

Poole

Torquay

Truro

Wolverhampton