A trial of defactinib and pembrolizumab for people with solid tumours (FAK-PD1)

Cancer type:

All cancer types
Lung cancer
Mesothelioma
Non small cell lung cancer
Pancreatic cancer

Status:

Open

Phase:

Phase 1/2

This trial is for people with solid tumours that have spread or continued to grow despite other treatments (advanced cancer). A solid tumour Open a glossary item is any type of cancer apart from those of the blood or lymphatic system such as:

  • leukaemia Open a glossary item
  • lymphoma Open a glossary item
  • myeloma Open a glossary item

Cancer Research UK supports this trial. 

More about this trial

Defactinib is a new drug that blocks substances (proteins) in the body called focal adhesion kinase (FAK). Drugs that can block these proteins are called FAK inhibitors.

We know from previous research that some cancer cells use these proteins to hide from the immune system Open a glossary item. Doctors think that blocking FAK might help other treatments, such as pembrolizumab, work better.

Pembrolizumab (Keytruda) is a targeted cancer drug (biological therapy) called monoclonal antibody. It helps the immune system to attack the cancer and stop it from growing.

Pembrolizumab is already used to treat certain types of cancer, but this is the first time defactinib and pembrolizumab will be given together.

This trial is in 2 parts (phases). In part 1 the researchers want to find the best dose of defactinib and to see if it is safe to have it with pembrolizumab.

Once researchers find the best dose, part 2 opens. In this part they are collecting information on how defactinib works and the effect it has in the body. Part 2 is for people with:

The main aims of this trial are to:

  • learn about the side effects of defactinib and pembrolizumab when given together
  • find the highest safe dose of defactinib which can be given with pembrolizumab 
  • find out how well defactinib and pembrolizumab work as a treatment
  • look for certain substances (biomarkers Open a glossary item) that can help to tell how well treatments work 

Who can enter

The following bullet points list 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.

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

  • Have at least 1 area of cancer that can be seen and measured on a scan and that has got worse after the last cancer treatment  
  • Have had all suitable treatments (standard treatment Open a glossary item) for your cancer or your doctor thinks pembrolizumab is a suitable treatment
  • Have a tissue sample of your cancer available that was taken either when you were diagnosed or during treatments (archival tissue sample) 
  • Are well enough to carry out your normal activities, apart from heavy physical work (performance status of 0 or 1) and this hasn’t change in the past 2 weeks
  • Have satisfactory blood tests results
  • Are able to swallow and absorb tablets   
  • Are at least 18 years old
  • Are willing to use reliable contraception during treatment and for 4 months afterwards if there is any possibility you or your partner could become pregnant

You may be able to join the 1st part of the trial if you have a solid tumour (not a leukaemia, myeloma or lymphoma) that has spread or continued to grow despite treatments.

You may be able to join the 2nd part of the trial if 1 of the following also apply. You:

  • Have adenocarcinoma of the pancreas
  • Have non small cell lung cancer (NSCLC) and you are happy to have new samples of tissue taken
  • Have mesothelioma that started in the sheets of tissue that cover the lungs (pleural mesothelioma) or in the tissue lining the inside of the tummy (peritoneal mesothelioma), and you are happy to have new samples of tissue taken

You cannot join this trial if any of these apply:

Cancer related

  • Your cancer has spread to your brain unless you have had treatment, it hasn’t got worse in the past 4 weeks and you are no longer taking steroids
  • You have had cancer treatment that reached your whole body (systemic) in the last month (6 weeks if you had the drug mitomycin C or chemotherapy from a group of drugs called nitrosoureas Open a glossary item)    
  • You have moderate or severe side effects from previous treatment apart from hair loss
  • You have had another cancer in the past 5 years apart from successfully treated early cancer (such as carcinoma in situ Open a glossary item of the cervix or non-melanoma skin cancer, or prostate cancer that has been stable for more than a year)

Medical conditions

  • You have taken part in another clinical trial in the past 4 weeks  
  • You are sensitive to defactinib, pembrolizumab or anything they contain
  • You have heart problems such as high blood pressure (hypertension) that isn’t controlled or you have had a heart attack
  • You have taken drugs that damp down your immune system such as steroids in the past 2 weeks, unless it was a very small amount or it was to replace something that the body makes such as cortisol   
  • You have or have had an autoimmune disease Open a glossary item that needed systemic treatment in the past 2 years, apart from treatment to replace something the body makes
  • You have lung problems such as interstitial lung disease or inflammation of the lung (pneumonitis)
  • You have a serious infection that isn’t controlled by medication
  • You have tuberculosis 
  • You have HIV
  • You have hepatitis B or hepatitis C
  • You have had a live vaccine Open a glossary item in the last month
  • You have any other serious medical condition that the trial team think could affect you taking part

Other

  • You are pregnant or breastfeeding 

Trial design

This is a phase 1/2 trial. The researchers need up to 59 people to take part.

This trial has 2 parts:

  • part 1 – doctors need around 12 people with a solid tumour to join this part
  • part 2 – doctors needs around 47 people with non small cell lung cancer (NSCLC), mesothelioma or pancreatic cancer to take part

Everyone has defactinib and pembrolizumab. The dose of defactinib you have depends on when you join the trial.

Part 1
The first few people taking part have a lower dose of defactinib and the normal dose of pembrolizumab. If they don’t have any serious side effects, the next few people have the normal dose of defactinib and pembrolizumab.

You take defactinib tablets twice a day, every day. And you have pembrolizumab as a drip into a vein every 3 weeks. It takes about 30 minutes each time.

You continue to have treatment for as long as it is helping you and the side effects aren’t too bad. You can have treatment for up to 2 years.

You may be able to continue to have defactinib and pembrolizumab after 2 years. This is called re-treatment. Your doctor can tell you more about this.

Part 2
This part of the trial is randomised for some people taking part. People with NSCLC and mesothelioma are put into 1 of the following treatment groups by computer:

  • defactinib and pembrolizumab
  • defactinib for 2 weeks and then defactinib and pembrolizumab

Neither you nor your doctor are able to decide which group you are in.

FAK-PD1 trial diagram

People with pancreatic cancer have defactinib and pembrolizumab.

You have the best dose of defactinib found in part 1. You have it as tablets that you take twice a day. And you have pembrolizumab as drip into a vein every 3 weeks.

You continue to have treatment for as long as it is helping you and the side effects aren’t too bad. You can have treatment for up to 2 years.

After 2 years you may be able to continue having treatment (re-treatment). Your doctor can tell you more about this.

Blood tests
You have extra blood tests as part of this trial. You have them before the start of treatment and then:

  • before the 1st and 2nd treatment with pembrolizumab (if you are in part 2)
  • at the same time you have a biopsy Open a glossary item (if you have this)
  • every 6 weeks for 6 months
  • every 12 weeks for 2 years
  • at the end of treatment

Doctors want to look for certain substances (biomarkers) that can tell how well the treatment works. If possible the extra blood samples are done at the same time as any routine blood tests. 

Tissue sample
The trial team will ask to use a tissue sample of your cancer taken either when you were diagnosed or during any treatment you have had.

You have extra tissue samples taken (biopsy) if you have NSCLC or mesothelioma. You have the biopsy before the start of treatment and then after 2 weeks.

Doctors might also ask you to have a biopsy if you have pancreatic cancer. This is only if they think it’s safe. You don’t have to agree to this if you don’t want to. You can still take part in this trial. 

Hospital visits

You see a doctor and have some tests before taking part. These tests might include:

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

During treatment you see the trial doctor for blood tests and a physical examination every 3 weeks. The research team might also phone you to check how you are.

You have a CT scan or MRI scan every 6 to 12 weeks. This continues for as long as your cancer stays the same and does not get worse. If your cancer gets worse you stop having defactinib and pembrolizumab.

When you finish treatment you see the trial team after a month. The trial team will then check with you or your doctor every 3 months to see how you are.

Side effects

This is the first time defactinib will be given with pembrolizumab so there may be side effects we don’t know about yet.

The trial team monitor you during the time you have treatment and you will be given a phone number to call them if you are worried about anything. The team will tell you about all the possible side effects before you start the trial.

The most common side effect of defactinib are:

We have information about pembrolizumab

Location

Belfast
Edinburgh
Glasgow
Leicester
Southampton

Recruitment start:

Recruitment end:

How to join a clinical trial

Please note: In order to join a trial you will need to discuss it with your doctor, unless otherwise specified.

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Chief Investigator

Dr Stefan Symeonides
Professor Christian Ottensmeier
Professor Jeff Evans
Professor Dean Fennell
Dr Vicky Coyle

Supported by

Cancer Research UK
Cancer Clinical Trial Unit Scotland (CaCTUS)
MSD
NHS Greater Glasgow and Clyde
Queens’ University Belfast
University of Edinburgh
University of Glasgow
University of Leicester
University of Southampton
Verastem

Other information

This is Cancer Research UK trial number CRUKD/16/008

We have more information about Professor Dean Fennell.

Questions about cancer? Contact our information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

14132

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Over 60,000 cancer patients enrolled on clinical trials in the UK last year.

Last reviewed:

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