A trial looking at a vaccine, chemotherapy and an immunotherapy for non small cell lung cancer

Cancer type:

Lung cancer

Non small cell lung cancer

Secondary cancers

Status:

Open

This trial is looking at 2 vaccines with standard treatment for non small cell lung cancer that has spread from where it started.

Cancer Research UK supports this trial.

More about this trial

One of the standard treatments Open a glossary item for non small cell lung cancer (NSCLC) is chemotherapy and immunotherapy . The chemotherapy can be either:

The immunotherapy can be pembrolizumab.

In this trial researchers are looking at the ChAdOx1-MAGEA3-NYESO vaccine and the MAGE-A3 vaccine.

MAGE-A3 and NYESO-1 are proteins found on some cancer cells. Not everyone has them and not every cancer type has these proteins.

The vaccines contain harmless parts of the MAGE-A3 and NYESO-1 proteins. The vaccines work by helping the immune system Open a glossary item find the proteins. The immune system recognizes them as something foreign in the body and attacks them.

Laboratory studies Open a glossary item have shown that the vaccines help the immune system recognize and attack cancer cells with these proteins.

Researchers want to find out if this happens when people with cancer have the vaccines.

There are 2 parts to this trial. In the first part a small number of people have the vaccines with the standard treatment. The team want to find out how safe it is to give them with standard treatment.

In the second part you either have:

standard treatment by itself
standard treatment and the vaccines

The aims of this trial are to find out:

how safe it is to have the vaccines with standard treatment
how acceptable it is
how well the vaccines work with standard treatment
what happens in the body after having the vaccines
more about the side effects

Who can enter

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 squamous cell non small cell lung cancer (NSCLC) that is over 5 cm across, has spread to lymph nodes or nearby organs (stage 3B or 3C). Or your cancer has spread to both lungs or another part of the body (stage 4). You can also join if you have a non squamous NSCLC that is stage 3B or stage 4.
are to have pembrolizumab and chemotherapy but you have not started treatment yet
have an area of cancer that the doctor can measure
have a tissue sample that shows less than half (50%) of the cancer cells have the protein PD-L1 and has a protein (biomarker ) called MAGE-3A
are fit and active but might not be able to do heavy physical work (performance status 0 or 1)
have satisfactory blood test results
are willing to use 2 types of contraception during treatment and for a time after if you or your partner could become pregnant
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 had chemotherapy and or radiotherapy for your NSCLC unless it was completed 6 months before your diagnosis of cancer spread
have already had an immunotherapy
have or had another cancer apart from successfully treated non melanoma skin cancer , early cancer (non muscle invasive) of the bladder or a carcinoma in situ
have cancer spread to the brain, spinal cord or tissue surrounding the brain. You might be able to join if it is treated, has not got worse and doesn’t need treatment.

Medical conditions

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

have major chest surgery or tummy (abdominal) surgery and have not recovered fully
have a heart trace (ECG ) that shows your heart rhythm isn’t normal. Your doctor will test for this and tell you the results.
have an active infection or similar disease that affects your whole body
have HIV, hepatitis B or hepatitis C
have an auto immune disease apart from certain ones. Your doctor will know which ones these are.
have had the AstraZeneca COVID-19 vaccine (also called Vaxzevria) within 6 weeks of starting treatment
have an immune system that isn’t working well or you are taking medication that damps down the immune system. This is apart from a small daily dose of steroids.
have had a stem cell transplant from a donor (allogeneic transplant) within the past 5 years. You might be able to join if your transplant was more than 5 years ago and you have no symptoms of graft versus host disease (GvHD).
have a history of having a low count of a blood cells called platelets after having heparin (This is HITT or HIT type 2.)
are taking part or going to take part in another clinical trial that uses an experimental drug
have any other medical condition or mental health problem that could affect you taking part

Other

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

are allergic to an immunotherapy, any ChAdOx1 or MAV vaccines or any of their ingredients
have a severe allergy to eggs or to another vaccine
have a live vaccine within in 4 weeks of joining the trial. The COVID-19 vaccines aren’t live vaccines. But you can’t have these vaccines within a certain time before and after the trial vaccine. Your doctor will know how long this is.

Trial design

This is a phase 1/2 trial. There are 2 parts to this trial.

In the first part the team need up to 6 people to join. All have the vaccines with the standard treatment. They are monitored for any side effects. This is to make sure it is safe to give the vaccines with chemotherapy and pembrolizumab.

For the second part the team need 80 people to join. This part is a randomised trial. A computer puts you into 1 of 2 groups. Neither you nor your doctor can choose which group you are in. The groups are:

standard treatment and the vaccines
standard treatment

17225-randomisation_002.png

Standard treatment
This is either:

pembrolizumab, pemetrexed and cisplatin or carboplatin
or pembrolizumab, paclitaxel and carboplatin

Your doctor will talk to about which is best treatment for you.

Pembrolizumab, pemetrexed and cisplatin or carboplatin
You have pembrolizumab, pemetrexed and cisplatin or carboplatin as a drip into a vein. You have them every 3 weeks. This is a cycle of treatment Open a glossary item .

After 4 cycles of treatment you then have either:

pembrolizumab every 3 weeks for about 2 years (35 cycles) or
pembrolizumab and pemetrexed every 3 weeks for about 2 years (35 cycles) or
a higher dose of pembrolizumab every 5 weeks for 2 years

Pembrolizumab, paclitaxel and carboplatin
You have pembrolizumab, paclitaxel and carboplatin as a drip into a vein. You have them on the same day every 3 weeks. This is a cycle of treatment. You have 4 cycles of treatment.

You then have pembrolizumab:

at the same dose every 3 weeks for about 2 years (35 cycles) or
at a higher dose every 6 weeks for up to 2 years

Vaccines
You have the vaccines as an injection into a muscle. You have them in the muscle at the top of the arm, top of the leg or the buttocks. You have them in the same muscle all the time unless it becomes sore or there is a reaction.

You have the first vaccine just before you have your 3rd cycle of treatment (9 weeks). You then have the second vaccine before you have the 4th cycle of treatment (12 weeks).

If you continue with the standard treatment you might have the first vaccine again before the 8th cycle of treatment. And the second vaccine before the 9th cycle of treatment.

Patient diary cards
You have a diary cards to complete every day. The team explains how to use them. You record details about:

the injection site
your general wellbeing

You must bring the cards with you when you attend your hospital appointments.

Samples for research
The team take extra blood samples during the trial. Where possible they take these when you have your routine bloods done.

Researchers use these samples to find out:

how well the vaccines are working
why the treatment might work better for some people

Hospital visits

You see the doctor to have tests before taking part. These tests include:

•   a physical examination Open a glossary item
•   blood tests
•   CT scan or an MRI scan
•   urine test
•   heart trace (ECG )

Everyone sees the doctor at regular times during treatment. This is for blood tests and to see how you are. You also have another CT scan or MRI scan.

Before your 10th cycle of treatment (between 30 and 60 weeks) you see the doctor. This is for blood tests and to see how you are. This is your last visit for the trial.

If you have side effects caused by the vaccines you see the doctor every month until the side effects are gone. Where possible these will be at the same time you have your routine appointments.

Side effects

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.

This is the first time the ChAdOx1-MAGEA3-NYESO vaccine and MVA-MAGE3 vaccine are being used in humans. There might be side effects we don’t know about yet. Based on similar vaccines and laboratory studies the possible side effects might include:

a reaction at the injection site such as redness, itching, swelling, feeling warm and a rash
tiredness and lack of energy (fatigue)
flu-like symptoms
joint and muscle pain
a drop in blood cells causing an increased risk of infection, bruising, bleeding and shortness of breath
an allergic reaction
changes to how well your heart works
feeling sick

Pembrolizumab and the vaccines can affect the immune system. They may cause inflammation in different parts of the body. This can cause serious side effects. These side effects could happen during treatment, or some months after treatment has finished. Rarely, these side effects could be life threatening.

If you have any of these side effects tell your doctor or nurse as soon as possible. You should tell them that you are on or have been on an immunotherapy.

We have information about:

•   pembrolizumab
•   paclitaxel and carboplatin
•   pemetrexed and cisplatin
•   pemetrexed and carboplatin

Your doctor or a member of the trial team will talk to you about the possible side effects of the treatments before you agree to take part in the trial.