*ASTX029 in Advanced Solid Tumours
Research type
Research Study
Full title
A Phase 1-2 Study of the Safety, Pharmacokinetics, and Activity of ASTX029 in Subjects With Advanced Solid Tumors
IRAS ID
290662
Contact name
Matthew Krebs
Contact email
Sponsor organisation
Astex Pharmaceuticals, Inc.
Eudract number
2018-004568-72
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
IND Number, 134813
Duration of Study in the UK
2 years, 1 months, 1 days
Research summary
Summary of Research
There are around 367,000 new cancer cases in the UK every year. Over the last decade, incidence rates for all cancers combined have increased by a twentieth (5%) in the UK.Historically, medical approaches to treat advanced cancers have typically involved surgery, radiotherapy, and/or chemotherapy. Scientific advances have led to successful development of therapies targeting specific mutations in cancer cells. More recently, cancer immunotherapy has also been shown to significantly improve the outcomes of many cancers. However, a significant proportion of patients eventually relapse. There is an unmet need for new approaches to stop the uncontrolled growth of cancer cells in patients whose tumours have progressed despite currently available treatments.
ASTX029 has been shown to help slow the growth of some tumours in laboratory tests. The purpose of this study is to determine the best dose to use for treating patients and if the medication is effective in patients who are not eligible for other approved treatments.
The study will enrol participants who have tumours with specific gene mutations that may make them more sensitive to the medication. The study medication will be taken once a day and participants will be required to fast for four hours when taking their medication.
Participants may continue to receive study medication for as long they receive benefit from it, until a decision is made to stop the treatment.
It is anticipated that up to 300 participants will be enrolled in this study.
Summary of Results
A Study to Learn About the Safety and Effects of ASTX029 in People With Advanced Solid TumoursProtocol : ASTX029-01
Study dates: May 2018 to March 2025
Many thanks to the participants who took part in the study.
This study helped researchers learn more about the investigational medicine, ASTX029, in people with an advanced solid tumour. An investigational medicine is one that is being studied as a possible treatment for a disease or condition. It has not been approved for use outside of clinical studies.
Why was this study done?
Researchers are looking for new treatments to help people with advanced solid tumours.
Cancer is a disease where cells grow and divide out of control. Solid cancers are lumps of abnormal cells formed in different parts of the body, such as breasts, lungs, or skin. Advanced solid tumours are cancers that have spread from their original site to other parts of the body, making them more difficult to treat.
In advanced cancers, a process inside cells called the MAPK pathway, which normally helps control cell growth, becomes overactive. This causes proteins called ERK, which are part of the pathway, to stay active all the time, leading to uncontrolled growth and spread of cancer cells.
Chemotherapy is the most common treatment used for cancer. It uses medicines to kill fast-growing cancer cells. When cancer spreads or becomes harder to treat, it is often managed with surgery, radiation therapy, or chemotherapy. However, cancer can come back even after treatment or stop responding to treatments. That is why researchers are studying new treatments.
ASTX029 is a new medicine being developed as a possible treatment for advanced cancer. It is designed to stop the ERK proteins from becoming active and also blocks their activity if they are already active. This may slow down or stop the growth of cancer cells.
This study was the first time that ASTX029 was tested in people. Researchers tested increasing doses of AXTX029 to find a dose that could be safely used for further study. They also checked if the medicine could help slow down or stop cancer from growing. This study included people who had advanced solid tumours without suitable approved treatment options available.This study was done in 2 phases. The main questions that researchers wanted to answer were:
Phase 1
• How many participants had dose-limiting toxicities?
• How many participants had medical problems?
Medical problems are unwanted health problems that happen during the study. They may or may not be related to the study medicine.
• How many participants had serious medical problems?
A medical problem is considered ‘serious’ if it leads to death, is life-threatening, causes long-term issues, or requires hospital care.Phase 2
• How many participants had their tumours shrink or disappear during the study?When was this study done?
This study started in May 2018 and ended in March 2025.Who took part in this study?
Participants could take part if they:
• Were at least 18 years old.
• Had advanced solid tumours.
• Their cancer had spread and could not be removed by surgery.
• Did not respond to previous standard cancer treatments.
Participants could not take part if they:
• Were allergic to the study medicine, ASTX029, or any of its ingredients.
• Had serious health problems such as damage to major organs, or heart disease.
• Had received cancer treatments like chemotherapy, or radiation, within 4 weeks before receiving the study medicine.
For more information on who could take part in this study, please refer to the details provided at the end of this summary.How many people took part in this study?
A total of 192 people with advanced solid cancer enrolled in the study, of which, two died before they could start the treatment.
During the study, 190 participants, aged between 25 and 86 years, received the study treatment.
The study took place at clinical sites in the United States, France, Spain, and the United Kingdom.
What treatments were studied?
Researchers studied the following treatment:
• ASTX029: starting dose of 10 milligrams (mg) to 280 mg.
- At first, ASTX029 was given as a powder in a bottle. This powder had to be mixed with a liquid before taking it. The mixed medicine could be swallowed or given through a feeding tube.
- Once researchers collected enough information using this method, they stopped using the powder form.
- After that, ASTX029 was given as a tablet(s) by mouth, once a day.Participants received treatment in a 21-day (3-week) cycle. Every 21 days of treatment during the treatment period is called a Cycle.
What happened during the study?
There are many types of clinical studies. This study was:
• Phase 1/Phase 2: In a Phase 1/Phase 2 study, a new treatment is tested in a small number of participants. Researchers check its safety and how the treatment works in the body.
• Open label: Both the researchers and participants know the study medicine and dose received.How was the study done?
This study tested ASTX029 in people aged 18 or older with advanced solid cancer, which did not get better with the standard treatments.This study was conducted in the following process:
• Screening (to check if people could join)
• Participants were screened before they could join the study. At the screening visit, participants had a physical exam, and their medical history was checked.
• Participants had several health tests done:
o Blood and urine tests
o Heart tests
o Questions about health and well-being
o Imaging scans to check for tumours
o Tumour samples to check for the growth of cancer
• Throughout the study, researchers continued to do these tests regularly to monitor participants’ health.Treatment Period
The study was done in 2 parts: Phase 1 and Phase 2.Phase 1
During Phase 1, researchers wanted to find out the best dose of ASTX029 that was safe for participants to receive.
This phase had 2 parts:
• Part A (finding the right dose):
o Participants were started on the lowest dose of ASTX029. If there were no safety concerns after participants completed the first treatment cycle, a higher dose of ASTX029 was tested in the next group.
o The doses were increased until researchers found the best dose of ASTX029 that was safe and well tolerated by participants.
o Part A had 12 groups that received different doses of ASTX029.• Part B (testing the chosen dose):
Based on all the safety data from Part 1, researchers chose the safe doses of ASTX029 to be tested in a larger group of participants. This helped them learn more about the safety of ASTX029 and how it worked in the body.Participants visited the clinics regularly for health checks and tests, including scans, to check if their cancer was getting better.
Phase 2
Researchers wanted to test ASTX029 further in more participants to see if it worked well and was safe at the chosen dose.
Participants were divided into 6 groups based on the type of cancer and gene changes, as follows:
• Group A: Melanoma with NRAS gene changes (32 participants)
• Group B: Lung cancer with KRAS gene changes (15 participants)
• Group C: Cancers with BRAF V600 gene changes (12 participants)
• Group D: Cancers with BRAF-fusion gene changes (9 participants)
• Group E: Cancers in reproductive organs with MAPK gene changes (32 participants)
• Group F: Other cancers with MAPK gene changes (15 participants)Participants continued the treatment until their cancer became worse, they had serious medical problems, they chose to stop, or the study ended.
• After treatment
Participants had a final check-up 30 days after the last dose of ASTX029 to see how they were feeling and if they had any medical problems.What were the results?
The results below include all 190 participants who received ASTX029.
Phase 1
How many participants had dose-limiting toxicities?
During Phase 1, researchers wanted to find out the best dose for participants to receive.
To do this, they closely monitored participants for dose-limiting toxicities during the 1st treatment cycle.
Dose-limiting toxicities are medical problems that are so serious they stop doctors from giving higher doses of the medicine. These medical problems help determine the highest safe dose for treatment.
Researchers found that:
• In Phase 1 – Part A
o 2 of 56 participants (4%) had dose-limiting toxicities.
• In Phase 1 – Part B
o None of the participants had a dose-limiting toxicity.How many participants had medical problems?
Medical problems are unwanted health problems that happen during the study. They may or may not be related to the study medicine.
Researchers monitored the participants’ health and checked for medical problems throughout the study.Researchers found that:
• In Phase 1 – Part A
o 56 of 56 participants (100%) had medical problems.
• In Phase 1 – Part B
o 20 of 20 participants (100%) had medical problems.How many participants had serious medical problems?
Researchers looked at any serious medical problems that participants had during the study. A medical problem is considered ‘serious’ if it leads to death, is life-threatening, causes long-term issues, or requires hospital care. All the serious medical problems that may or may not be caused by ASTX029 are reported as follows:
Researchers found that:
• In Phase 1 – Part A
o 21 of 56 participants (38%) had serious medical problems
• In Phase 1 – Part B
o 9 of 20 participants (45%) had serious medical problems.Phase 2
How many participants had their tumors shrink or disappear after treatment?
Researchers looked at how many participants had their tumours shrink or disappear after treatment. To check this, they used a set of criteria called Response Evaluation Criteria in Solid Tumours (RECIST). It helps evaluate the tumour size and amount, and determine if the cancer is growing, shrinking, or remaining stable during treatment. It enables researchers to measure how well a cancer treatment is working.
Researchers found that:
• In Group A, 4 out of 32 participants (13%) had their tumours shrink or disappear
• In Group B, None of the 15 participants (0%) had their tumours shrink or disappear
• In Group C, 1 out of 12 participants (8%) had their tumours shrink or disappear
• In Group D, None of the 9 participants (0%) had their tumours shrink or disappear
• In Group E, 4 out of 32 participants (13%) had their tumours shrink or disappear
• In Group F, 1 out of 14 participants (7%) had their tumours shrink or disappearOverall, 10 out of 114 participants (9%) had their tumours shrink or disappear after receiving treatment with ASTX029.
For more information on the study results, refer to the details provided at the end of this summary.What side effects did participants have during the study?
Medical problems may or may not be caused by the study medicine. When medical problems are thought to be related to the study medicine, they are called side effects. A side effect is called ‘serious’ if it leads to death, is life-threatening, causes long-term issues, or requires hospital care.
The results of multiple clinical studies are needed to learn whether a side effect is truly caused by a study medicine. The side effects that happened during this study are summarised below. Other studies about ASTX029 may report other side effects.
Summary of side effects
Participants who received less than 200 mg ASTX029 (32 participants)
• How many participants had any side effects? 66% (21 participants)
• How many participants had serious side effects? 6% (2 participants)
• How many participants left the study due to side effects? 0% (0 participants)
• How many participants died during the study? 0% (0 participants)Participants who received 200 mg ASTX029 (151 participants)
• How many participants had any side effects? 83% (126 participants)
• How many participants had serious side effects? 1% (2 participants)
• How many participants left the study due to side effects? 0% (0 participants)
• How many participants died during the study? 0% (0 participants)Participants who received 280 mg ASTX029 (7 participants)
• How many participants had any side effects? 100% (7 participants)
• How many participants had serious side effects? 0% (0 participants)
• How many participants left the study due to side effects? 0% (0 participants)
• How many participants died during the study? 0% (0 participants)What serious side effects were reported?
All participants who had serious side effects are reported here. Some participants had more than one serious side effect – this means that they are included in more than one side effect listed below.
An infection in the tubes that carry bile from the liver to the small intestine (Biliary tract infection) Participants who received less than 200 mg ASTX029: 3% (1 out of 32 participants) Participants who received 200 mg ASTX029: less than 0% (0 out of 151 participants) Participants who received 280 mg ASTX029: 0% (0 out of 7 participants)Feeling generally unwell (Malaise)
Participants who received less than 200 mg ASTX029: 3% (1 out of 32 participants) Participants who received 200 mg ASTX029: less than 0% (0 out of 151 participants) Participants who received 280 mg ASTX029: 0% (0 out of 7 participants)Higher than usual levels of a liver enzyme called aspartate aminotransferase in the blood (Aspartate aminotransferase increased):
Participants who received less than 200 mg ASTX029: 0% (0 out of 32 participants) Participants who received 200 mg ASTX029: less than 1% (1 out of 151 participants) Participants who received 280 mg ASTX029: 0% (0 out of 7 participants)Higher than usual levels of a liver enzyme called alanine aminotransferase in the blood (Alanine aminotransferase increased):
Participants who received less than 200 mg ASTX029: 0% (0 out of 32 participants) Participants who received 200 mg ASTX029: less than 1% (1 out of 151 participants) Participants who received 280 mg ASTX029: 0% (0 out of 7 participants)Vomiting:
Participants who received less than 200 mg ASTX029: 0% (0 out of 32 participants) Participants who received 200 mg ASTX029: less than 1% (1 out of 151 participants) Participants who received 280 mg ASTX029: 0% (0 out of 7 participants)What were the most common side effects reported?
The top 5 most common side effects that happened during the study are reported here.
Loose, watery, and more frequent stools (Diarrhoea):
Participants who received less than 200 mg ASTX029: 16% (5 out of 32 participants) Participants who received 200 mg ASTX029: 42% (63 out of 151 participants) Participants who received 280 mg ASTX029: 57% (4 out of 7 participants)Wanting to throw up (Nausea):
Participants who received less than 200 mg ASTX029: 34% (11 out of 32 participants) Participants who received 200 mg ASTX029: 25% (38 out of 151 participants) Participants who received 280 mg ASTX029: 43% (3 out of 7 participants)Feeling tired or weak (Fatigue):
Participants who received less than 200 mg ASTX029: 6% (2 out of 32 participants) Participants who received 200 mg ASTX029: 21% (32 out of 151 participants) Participants who received 280 mg ASTX029: 29% (2 out of 7 participants)Vomiting :
Participants who received less than 200 mg ASTX029: 16% (5 out of 32 participants) Participants who received 200 mg ASTX029: 14% (21 out of 151 participants) Participants who received 280 mg ASTX029: 14% (1 out of 7 participants)A skin rash that looks like acne (Dermatitis acneiform):
Participants who received less than 200 mg ASTX029: 3% (1 out of 32 participants) Participants who received 200 mg ASTX029: 17% (25 out of 151 participants) Participants who received 280 mg ASTX029: 14% (1 out of 7 participants)How has this study helped patients and researchers?
This study helped researchers learn about the safety of ASTX029 and find out the best dose for future treatments. Researchers found ASTX029 was safe and tolerable in people with advanced solid tumours. Overall, around 9% of participants had their tumours shrink or disappear after receiving treatment with ASTX029.
The results from this study may be used in other studies to learn more about the use of ASTX029 as a possible treatment for advanced solid tumours.Are there plans for further studies?
There are no current or planned studies of ASTX029 by Taiho Oncology, Inc. Another sponsor, Mosaic Therapeutics, may explore future studies with this medicine.Where can I find out more about this study?
• Official Title of this Study: A Phase 1-2 Study of the Safety, Pharmacokinetics, and Activity of ASTX029 in Subjects With Advanced Solid Tumors• Protocol Number: ASTX029-01
• ClinicalTrials.gov ID: NCT03520075
• EU Study Number: 2018-004568-72REC name
East Midlands - Derby Research Ethics Committee
REC reference
22/EM/0190
Date of REC Opinion
21 Apr 2021
REC opinion
Further Information Favourable Opinion