A study looking at INCB106385 for advanced solid cancers

Cancer type:

Anal cancer

Bladder cancer

Bowel (colorectal) cancer

Breast cancer

Gastro oesophageal cancer

Head and neck cancers

Kidney cancer

Laryngeal cancer

Liver cancer

Lung cancer

Mouth (oral) cancer

Non small cell lung cancer

Ovarian cancer

Pancreatic cancer

Pharyngeal cancer

Prostate cancer

Stomach cancer

Status:

Open

Phase:

Phase 1

This study is looking at a drug called INCB106385 by itself or with another drug called retifanlimab (INCMGA00012) for some solid cancers. It is open to people with cancer that has spread to another part of the body or the nearby tissue (advanced cancer).

A solid cancer Open a glossary item is any cancer apart from blood cancers such as leukaemia and lymphoma.

More about this trial

INCB106385 is an immunotherapy Open a glossary item called an immunosuppressive metabolite. It works by blocking a substance called adenosine. Adenosine is responsible for suppressing the body’s immune response. Blocking adenosine helps the immune system fight cancer.

This is the first time that INCB106385 has been used in cancer patients. But it has been tested in healthy volunteers. Researchers need to find the best dose of INCB106385 for people with cancer to take. The best dose is the dose that helps the most and has the fewest side effects.

Retifanlimab is an immunotherapy called a checkpoint inhibitor. It works by blocking a protein called PD-1. Blocking PD-1 can help the immune system fight cancer.

The researchers know the best dose of retifanlimab to give. This is because a small number of cancer patients have had it.

In this study the team want to know what the best dose of :

INCB106385 is to have by itself
INCB106385 is to have with retifanlimab

So in this study some people have INCB106385 by itself and some have it in combination with retifanlimab.

The aims of this study are to find:

what is the best dose of INCB106385 to have by itself and in combination with retifanlimab
out more about the side effects of INCB106385 by itself
out about the side effects of INCB106385 combined with retifanlimab
how acceptable these treatments are

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.

There are 2 parts to this study. The 2nd part is not open to people with some of the cancer types listed below. Your doctor will know which ones these are.

Who can take part

You may be able to join this study if you have one of the following:

anal cancer
transitional (urothelial) bladder cancer
bowel (colorectal) cancer
triple negative breast cancer
liver cancer
non small cell lung cancer
laryngeal cancer
mouth (oral cavity) cancer
ovarian cancer or related cancers, such as fallopian tube cancer and primary peritoneal cancer
pancreatic cancer
cancer of the hypopharynx or oropharynx
prostate cancer
stomach cancer
cancer of the gastroesophageal junction

Some of the above cancers must be a squamous cell Open a glossary item carcinoma. Your doctor will know which ones they are and if your cancer is a squamous cell carcinoma.

And all of the following apply. You:

have cancer that has spread to the nearby tissue or to another part of the body
are willing to have samples of tissue (biopsy ) taken from your cancer before starting treatment and during treatment
have cancer that has CD8 T cells apart from prostate cancer. The team will test one of your tissue samples to find this out.
have an area of cancer the doctor can measure by CT scan or an MRI scan
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 contraception during treatment and for a certain 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 cancer spread to the brain or spinal cord. You might be able to join if it has been treated, is stable and you don’t need steroids for at least 1 week before study treatment.
have another cancer that needs treatment or is getting worse within the past 2 years. This is apart from successfully treated non melanoma skin cancer , in situ cancer of the cervix and other early cancers that were treated with the aim to cure and there has been no sign of it for more than a year.
still have side effects from previous treatment. This is apart from hair loss. And some other side effects that your doctor will know about.
have had treatment with a drug that works in a similar way to INCB106385. Your doctor will know if you have.
have had other cancer treatment including experimental drugs within a certain time of starting study treatment. You doctor will know what the time is for which drugs.

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

have had a heart attack, chest pain (angina) in the past 6 months or any other heart problems
have an autoimmune disease that needed systemic treatment in the past 2 years. This is apart from certain autoimmune diseases. Your doctor will know which ones.
have an immune system that isn’t working very well. You are taking medication such as steroids that affect how well your immune system works.
have a disease of the lung tissue. You have inflammation of the lung that is active and not infectious.
have ongoing complications from previous surgery
are taking medication that affects the CYP enzymes. You might be able to join if you can stop taking these before starting the study treatment. Your doctor will know which drugs affect CYP enzymes.
have HIV, COVID-19, active hepatitis B, hepatitis C or any active infection needing treatment or a past infection that is at a risk of becoming active again. You can talk to your doctor about this.
had an antibiotic within 28 days of starting the study treatment
have a problem with your digestive system that affects how well your body can absorb medication
have had an organ transplant . This includes a stem cell transplant from a donor (allogenic transplant ).
have any other medical condition or mental health problems that could affect you taking part

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

have a live vaccine within 30 days of starting study treatment
are allergic to the treatment or any of its ingredients
are pregnant or breastfeeding

Trial design

This is a phase 1 study. It is in 2 parts

The team needs a total of up to 306 people to take part:

81 people in part 1
225 people in part 2

In both parts some people have INCB106385 by itself. And some people have INCB160385 and retifanlimab.

In part 1 the team wants to find the best dose of INCB106385 to have by itself. They also want to find the best dose of INCB106385 when given together with retifanlimab. The best dose is the dose that helps the most and has the fewest side effects.

To find the best dose the first few people have a small dose. If they don’t have any problems then the next few have a higher dose. And so on until the team finds the best dose to give.

Part 2 starts when the team has found the best dose of INCB106385 to have by itself and the best dose of INCB106385 to have with retifanlimab.

What dose you have and whether you have INCB106385 by itself or with retifanlimab depends on when you join the study. Your doctor will tell you about this when you join the study.

INBC106385 is a tablet. You take it with a glass of water. Your doctor will tell you how many to take and when.

Some days you have a blood sample taken at the hospital before you take your dose of INCB106385. On these days you must not eat or drink for at least 2 hours before your visit to hospital. You then take INCB106385 after the blood sample collection and may have more blood taken afterwards. Your doctor will tell you beforehand when these days are.

You have retifanlimab as a drip into a vein. You have it every 4 weeks at the hospital.

You can have treatment for a maximum of 2 years as long as it is helping and the side effects aren’t too bad.

Samples for research
You have a sample of cancer tissue (biopsy Open a glossary item ) taken before you start treatment and then during week 5 or week 6 of treatment. You must agree to these to take part.

The team might ask to take another biopsy during treatment. This biopsy is optional. You don’t have to agree to it.

You give several blood samples during the study. Your doctor will tell you more about when and how often these are.

Researchers use the tissue and blood samples to find out:

how well treatment is helping
what happens to INCB106385 and retifanlimab in the body
how INCB106385 and retifanlimab affects the body
more about substances (biomarkers ) that might provide more information about how well treatment is helping

Hospital visits

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

a physical examination
blood tests
heart trace (ECG )
urine test
a CT scan, an MRI scan or PET scan

You see the doctor at regular times during treatment. This is to see how you are, for blood tests and to ask about side effects.

You have a scan every 8 weeks during treatment. After a year this might be every 12 weeks. Your doctor will talk to you about this after a year of treatment.

You see the doctor when you stop treatment. This is to see how you are.

You then see the doctor a month and again 3 months later. This is to see how you are and if you have any 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.

INCB106385 and retifanlimab are immunotherapies. They can affect the immune system. They may cause inflammation in different parts of the body. This can cause serious side effects. They could happen during treatment, or some 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.

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.

INCB106385 and retifanlimab are new drugs. The combination of these 2 drugs is also new. There might be side effects we don’t know about yet.

INCB106385 has been used in healthy people before. In a completed study of different doses of INCB106385 in healthy volunteers. The side effects that occurred most frequently included:

headache
abdominal pain
dizziness
feeling sick
abnormal feeling of pins and needles
feeling your heart is racing or pounding
changes to how your kidneys work which can cause passing urine more often or less often, swelling due to too much fluid in the body, muscle cramps and weakness
lack of energy, feeling weak or poor physical condition
back pain
pain in the muscles, bones and nerves of the chest
constipation or diarrhoea
loss of appetite
cough
dry skin and or itchy skin

Since the start of the study a small number of people have had the combination of INCB106385 and retifanlimab. The side effects that have been reported are:

a drop in red blood cells causing weakness and tiredness
lack of energy, weakness or poor physical condition
an increase of alkaline phosphatase in the blood which might be caused by liver damage or a bone problem
feeling sick
high temperature
pain where the cancer is

A small number of people have had INCB106385 either by itself or in combination with another drug. Side effects reported by at least 2 people are:

abdominal pain
lack of energy, feeling weak or poor physical condition
pain in the back, muscles, bones and nerves of the chest
constipation or diarrhoea
feeling or being sick
loss of appetite
cough
change to how well the kidneys work that may cause no symptoms or can cause muscle cramps, weakness, changes to how often you pass urine and or holding water in the body
dry or itchy skin

Based on animal studies the following side effects of INCB106385 may be possible in humans. They include:

skin problems such as itching, redness and a rash
inflammation of the lungs, salivary glands, thyroid, kidneys, pancreas, prostate, colon
stomach ulcers
tissue and organs that make hormones (endocrine ) not working properly
watery eyes
liver injury
tiredness (fatigue)
lack of energy