A study looking at tolinapant with pembrolizumab to treat solid cancers (ASTEROID)
Cancer type:
Status:
Phase:
This study is looking at tolinapant (ASTX660) with pembrolizumab for people with cancer that has spread and whose treatment has stopped working.
It is for people with a 
. This is any cancer apart from a blood cancer such as leukaemia.
You pronounce tolinapant as tuh-lin-a-pant.
Cancer Research UK supports this study.
More about this trial
Pembrolizumab is an immunotherapy drug. Immunotherapy drugs work by activating the to find and kill cancer cells. These drugs work well, but unfortunately not for everyone.
show that some cancer cells are not recognized by the immune system. And so, the immune system can’t find and kill them. We know that one way for the immune system to recognize cancer cells is for the cancer cells to die.
Normal cells die after a certain time. This is called programmed cell death or . However, cancer cells can avoid apoptosis and so the immune system can’t recognize them.
Tolinapant is a . There are a family of proteins that can block apoptosis. Tolinapant works by blocking 2 of these proteins in the cancer cells. By doing so, tolinapant could cause the cancer cells to die and so make the cancer more recognizable to the immune system.
This study is in 2 parts. In the first part, the team want to find the best dose of tolinapant to have with pembrolizumab. In the second part, the team will look at using the best dose of tolinapant with pembrolizumab to treat solid cancers.
The aims of this study are to find out:
- the best dose of tolinapant to use with pembrolizumab
- how well this combination treatment works for solid cancers
- about the side effects of having tolinapant and pembrolizumab together
- how acceptable this treatment is for those taking part
- how this treatment affects people’s
quality of life
Who can enter
The following bullet points are a summary of the entry conditions for this study. Talk to your doctor or the study team if you are unsure about any of these. They will be able to advise you.
| The entry conditions below apply to everyone who might be able to take part. There are different groups in this study. As well as the below, each group has its own entry conditions which your doctor or member of the study team can tell you about. |
You may be able to join this study if all of the following apply. You:
- have a
solid cancer that is an advanced cancer - have had the
standard treatment for your cancer but it stopped working or there are no other standard treatment options, or you do not want the standard treatment - have an area of cancer that the doctor can measure
- have satisfactory blood test results
- are able to look after yourself but might not be able to do heavy physical work (performance status 0 or 1)
- are willing to use reliable contraception during treatment and for a period of time after if there is any chance you or your partner could become pregnant
- are at least 18 years old
Who can’t take part
Cancer related
You cannot join this study if any of these apply. You:
- have
radiotherapy , apart from for symptom control (palliative radiotherapy) within 4 weeks of joining the study - have
hormone therapy within 4 weeks of joining the study. This is apart from luteinising hormone blockers (LHRH) for men who are taking them for prostate cancer that has come back after having their testicles removed. And women with breast cancer that is hormone sensitive and are taking LHRH because they have not gone through the menopause . - have an
immunotherapy , including pembrolizumab, within 4 weeks of joining the study - have
chemotherapy within 4 weeks of joining the study. For nitrosoureas and mitomycin C it is 6 weeks. You can join if you are having bisphosphonates or a similar drug such as denosumab for cancer that has spread to the bones. - have an experimental drug as part of a clinical trial within 4 weeks of joining the study
- have another cancer apart from successfully treated
cone biopsy for carcinoma in situ of the cervix and successfully treated non melanoma skin cancer . You can join if you had cancer that was treated with the aim to cure, there has been no sign of the cancer coming back in the last 5 years and it has a low risk of coming back. - have had either a
stem cell transplant or a bone marrow transplant - have had radiotherapy that included a quarter (25%) or more of the
bone marrow within 8 weeks of joining the study
Some people may not be able to take part if they have cancer that has spread to the brain and spinal cord. And this cancer is active or has not been treated. This depends on the treatment group you take part in. Your doctor can tell whether this applies to you or not.
Medical conditions
You cannot join this study if any of these apply. You:
- have ongoing symptoms of a chronic medical condition or side effects from treatment that is moderate to severe. This is apart from hair loss and taking blood thinning medication such as warfarin to prevent another blood clot.
- have major surgery within 4 weeks of starting the study treatment
- have HIV, hepatitis B or hepatitis C. Or you are at a high medical risk due to another medical condition that affects the whole body such as an active infection that is not controlled.
- have scarring or inflammation of the lungs or had scarring or inflammation of the lungs that was treated with
steroids - have an
autoimmune disease that needed treatment within the past 3 months. This is apart from certain ones which your doctor will know about. - have an
immune system that is not working very well. Or you are taking medication that affects the immune system. This is apart from certain ones that your doctor will know about. - have certain
heart problems - are planning to or are taking part in another study or trial. You can join if it is an
observational study . - have had a drug similar to tolinapant (ASTX660). If you have had an
immunotherapy , you can join as long as you did not have any moderate to severe side effects from the immunotherapy. - have
digestive problems that could affect how well your body absorbs capsules - have had an
organ transplant - have symptoms of COVID-19 or you have COVID-19
- have any other medical condition, mental health condition or other circumstances that could affect you taking part
Other
You cannot join this study if any of these apply. You:
- are allergic or very sensitive to the treatments, or any of their ingredients, used in the study
- have a
live vaccine within 30 days of starting the study treatment. The COVID-19 and seasonal flu vaccines are not live vaccines. This is apart from the flu vaccine such as FluMist that you spray up the nose. - are pregnant or breastfeeding
Trial design
This is a phase 1 study. There are 2 parts:
- dose escalation
- dose expansion
Which part you are in depends on when you join the study.
Dose escalation- closed
In this part the team found the best dose of tolinapant to have with pembrolizumab. They will use this dose of tolinapant in the dose expansion part.
Dose expansion
In this part the team need 50 people to join.
There are 5 groups. Which group you go into depends on the type of cancer you have and the treatment you have had. This includes:
- 10 people with different types of advanced cancer such as melanoma skin cancer, renal cell kidney cancer, non small cell lung cancer and head and neck cancer. And the cancer has continued to grow or stayed the same following treatment with
checkpoint inhibitors . - 10 people with cervical cancer
- 10 people with a type of breast cancer called
triple negative breast cancer - 10 people with a type of brain tumour called a glioblastoma multiforme. Please note this group is closed.
- 10 people with breast cancer that is
oestrogen receptor positive and has low or no amounts of a protein called HER2 (HER2 negative). And the cancer has got worse despite treatment that targets a protein on the cancer cell called cyclin-dependent kinases 4 and 6.
When you start having tolinapant depends on your cancer type and whether you have had a before. Some people will start having pembrolizumab by itself and then later on may have tolinapant with pembrolizumab. Others will have tolinapant and pembrolizumab from the start. Your doctor will explain this more.
Tolinapant is a capsule. You take it for 1 week and then you don’t take it for 2 weeks. Each 3 week period is a . You can continue having tolinapant by itself as long as it is helping and the side effects aren’t too bad. Your doctor will discuss this with you.
You have pembrolizumab as a drip into a vein. You have it once every cycle of treatment at the start of week 2 of tolinapant. If you started pembrolizumab before starting tolinapant, you will have it once every cycle of treatment at the start of week 1 of tolinapant.
You continue to have pembrolizumab for 2 years as long as it is helping and the side effects aren’t too bad.
Samples for research - dose expansion
The team ask for blood samples. Where possible they will take these as part of your routine care.
They will ask for a tissue sample () before you start treatment, once during treatment and after you have stopped treatment. They will only do this if it is safe to do so and you agree to have the biopsies taken.
Quality of life
Everyone fills in questionnaires:
- before you start treatment
- during treatment
- at the end of treatment
The questions ask about:
- your general health and wellbeing
- what you are able to do
- side effects
These are quality of life questionnaires.
Hospital visits
You see the doctor for a and tests before taking part. These tests include:
You see the doctor regularly during treatment. This is:
- to see how you are
- for blood tests
- to ask about side effects
You see the doctor about a month after stopping treatment. The doctor will ask how you are and you have the same tests you had at the start.
Scans
You have a scan every 9 weeks. If you started pembrolizumab first you will have a scan at 6 weeks and then every 9 weeks.
Follow up
You see the doctor every 3 months for up to 2 years.
If you had side effects that your doctor thinks may be due to the treatment, they will you see every month until you no longer have these side effects.
Side effects
The study 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 most common side effects of tolinapant are:
- a drop in the red blood cells causing tiredness and breathlessness
- an increased level of two enzymes, lipase and amylase, in the blood
- a change to how the liver works
- diarrhoea
- feeling sick (nausea)
- a skin rash that could be itchy
- feeling tired (fatigue)
|
Pembrolizumab can affect the These side effects could happen during treatment or months after treatment has finished. Rarely, these side effects could be life threatening. Your doctor or nurse can explain what these side effects are, the risk of them happening and what to look out for. |
The most common side effects of pembrolizumab are:
- itchy skin, a skin rash and loss of skin colour
- diarrhoea
- cough
- joint, back and tummy (abdominal) pain
- high temperature (fever)
- a decrease in the hormones made by the
thyroid (hypothyroidism) causing weight gain, tiredness and lack of energy - low levels of salt in the blood, signs include feeling or being sick, headaches, confusion, tiredness, drowsiness, lack of energy and restlessness
We have more information about pembrolizumab.
Your doctor will tell you about the side effects of the treatments and answer any questions you might have before you agree to take part in the study.
Location
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.
Chief Investigator
Dr Juanita Lopez
Supported by
Cancer Research UK
Institute of Cancer Research (ICR)
Other information
This is Cancer Research UK trial number CRUK/21/016.
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
