BLU-667 in Lung Cancer, Thyroid Cancer and Other Solid Tumours
Research type
Research Study
Full title
A Phase 1/2 Study of the Highly-selective RET Inhibitor, BLU-667, in Patients with Thyroid Cancer, Non-Small Cell Lung Cancer (NSCLC) and Other Advanced Solid Tumors
IRAS ID
233393
Contact name
Martin Forster
Contact email
Sponsor organisation
F. Hoffmann-La Roche Ltd.
Eudract number
2016-004390-41
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
131825, IND Number
Duration of Study in the UK
5 years, 0 months, 0 days
Research summary
Summary of Research
This study is designed to learn about the side effects at different doses of an experimental drug called BLU-667 when it is given to patients with non-resectable advanced solid tumour cancers including non-small cell lung cancer (NSCLC) and thyroid cancers. Experimental means that it is not yet known if this drug helps patients as it has not yet been tested in humans and it is not available for sale. Non-resectable means that the tumour cannot be removed surgically. BLU-667 was designed to treat patients with tumours that have changes in the RET (Rearranged during Transfection) gene that may make the tumours grow. Changes in RET are found commonly in thyroid cancer and less commonly in other cancers such as NSCLC.
The study will be conducted at multiple medical centres in the USA, Europe and Asia and approximately 115 adult (at least 18 years old) patients will be enrolled.
This is a two part study involving a dose-finding part (Part 1) to find the most effective dose level of the study drug with the least side effects, and an expansion part (Part 2) to confirm that the chosen dose of the study drug is safe and well-tolerated, and to determine if the study drug causes tumours to shrink. Patients enrolled in the UK will only take part in Part 2.Summary of Results
Summary of Clinical Trial Results A study to look at whether pralsetinib worked in people with RET-altered solid tumours that have spread, including non-small cell lung cancer and thyroid cancer - and how safe this medicine was.This is a summary of the results of a clinical trial (called a 'study' in this document) - written for:
• Members of the public and
• People who took part in the study.This summary is based on information known at the time of writing.
The study started in March 2017 and finished in March 2024. This summary was written after the study had ended.No single study can tell us everything about the risks and benefits of a medicine. It takes lots of people in many studies to find out everything we need to know. The results from this study may be different from other studies with the same medicine.
This means that you should not make decisions based on this one summary - always speak to your doctor before making any decisions about your treatment.The people who took part have helped researchers to answer important questions about RET-altered solid tumours (including non-small cell lung cancer and thyroid cancer) that have spread, and the medicine studied - 'pralsetinib'.
Key Information about this study
Why was this study done?
• This study was done to see how safe a potential new treatment is for RET-altered cancer that has spread, and how well it works.
• RET-altered cancers can be RET-fusion or RET-mutated - they have alterations in a small section of DNA called the RET gene.
What was the medicine being studied and who was involved?
• In this study, people were given the medicine 'pralsetinib'.
• This study included 590 people in 13 countries.What were the results?
The main findings were that:
The recommended dose of pralsetinib was 400mg once a day.
Overall, people taking pralsetinib were able to continue taking it and function despite having unwanted effects.Around 24% of people (140 out of 590 people) taking pralsetinib had serious unwanted effects that were related to pralsetinib.
A positive response to treatment was seen in:
• 70% of people with RET-fusion non-small cell lung cancer
• 68% of people with RET-mutated thyroid cancer
• 85% of people with RET-fusion thyroid cancer
• 46% of people with other RET-altered solid tumoursBased on the results of this study, pralsetinib was approved by health authorities in:
The United States (U.S Food and Drug Administration) and China (National Medical Products Administration) for treating RET-altered lung cancer (known as 'non-small cell lung cancer') that has spread, and RET-altered thyroid cancer.Europe (European Medicines Agency) for treating RET-altered non-small cell lung cancer that has spread.
General Information about this study
Why was this study done?
Solid tumours are cancers that grow in organ systems throughout the body. These include cancers of the lung, thyroid, stomach and bladder. Some solid tumours have biomarkers, which can help doctors pick the best treatment for people with cancer. Biomarkers can be proteins, hormones, genes, or changes in genes (alterations). A gene is a section of DNA that has instructions for making the body and are passed on from parents to their children. Gene alterations can promote cancer growth.
Some solid tumours have a biomarker that is an alteration in the RET gene. This is known as 'RET-altered cancer'. The RET gene helps with development and growth before birth. Lung and thyroid cancers often have RET alterations, but other cancers can too.
RET-altered cancers include:
• RET-fusions: the RET gene isn't changed, but it joins with another gene, telling cells to keep growing • RET mutations: changes in the RET gene, either sudden or passed on from parents so that make it different from healthy cells.
These gene alteration biomarkers are not usually in healthy cells, so cancer medicines can use them to target cancer cells and leave healthy cells alone.What was the medicine being studied?
A medicine called 'pralsetinib' was the focus of this study.
• You say this as 'pral-SE-tee-nib.
• Pralsetinib is a targeted therapy for RET-altered cancers. It works by stopping the abnormal RET protein.
• This may mean that pralsetinib may stop RET-altered cancer cells from growing.
• Pralsetinib was first tested at different doses.What did researchers want to find out?
• Researchers did this study to find out how safe the medicine was - by checking how many people had unwanted effects and seeing how serious they were.
• They also wanted to see how well pralsetinib worked.
The study was in 2 parts - Phase 1 and Phase 2. In Phase 1 of the study, a small number of people first took pralsetinib. This was to find out how safe pralsetinib was and how well people tolerated increased doses. Then, in Phase 2 of the study, a larger number of people took pralsetinib.The main questions that researchers wanted to answer were:
1. For Phase 1 only: what was the highest dose that people could tolerate, and what was the recommended dose to use in Phase 2?
2. How many people had unwanted effects and how serious were they?
3. How many people with RET-altered cancer who were given the recommended dose had a positive response to the treatment?What kind of study was this?
This study was a 'Phase 1/Phase 2' study. Pralsetinib was given to people for the first time in this study.
This was an 'open-label' study. An open-label study means everyone involved, including the participant and the study doctor, know which study treatment the participant is given.
The study started in March 2017 and finished in March 2024. This summary was written after the study had ended.
The study took place at 84 study centres - across 13 countries in Asia, Europe and North America.Who took part in this study?
In this study, 590 people took part. They all had solid tumours that had spread to nearby tissue or to other parts of the body and could not be removed with surgery.
Most of the people in this study (571 out of 590) had RET-altered solid tumours.
People who took part in the study were between 18 and 87 years of age. 307 of the 590 people (48%) were male and 283 of the 590 people (52%) were female.People could take part in the study if:
• They were at least 18 years old
• They had a solid tumour that had spread to nearby tissue or to other parts of the body and could not be removed with surgery • They had a RET-altered solid tumour or a medullary thyroid cancerPeople could not take part in the study if:
• They had a mutation in a gene other than RET • They had uncontrolled heart or lung disease • They had cancer of the brain or spinal cord with worsening symptoms or required increasing steroid treatment, or cancer that had spread to the brain or spinal cord • They were pregnant or breastfeedingWhat happened during the study?
In Phase 1 of the study, groups of people were given different doses of pralsetinib, once or twice a day. This was to find out the safest recommended dose of pralsetinib that could be given in Phase 2 without unmanageable unwanted effects.
In Phase 2, a larger group of people took the recommended dose of pralsetinib. This was to see how safe pralsetinib was and how well it worked. People were divided into groups based on their cancer type, and some had already tried a treatment aimed at RET.
Pralsetinib (the medicine being studied) was given as capsules to be swallowed once or twice a day in Phase 1, and once a day in Phase 2 People in the study took the treatment for as long as it benefited them, or until they had unmanageable unwanted effects, or they decided to leave the study. When the study finished, the people who took part were asked to go back to their study centre for more visits - to check their overall health. Look below to see more information about what happened in the study.What were the results of the study?
Question 1: What was the highest dose that could be tolerated, and what was the recommended dose to use?
In Phase 1, researchers looked at the number, type and seriousness of unwanted effects that people had when given increasing doses of pralsetinib.
People were given between 30mg and 600mg of pralsetinib, once or twice a day.
The highest dose that could be given before people had unmanageable unwanted effects was 400mg once a day. This was the recommended dose used in Phase 2 of the study.
Question 2: How many people had unwanted effects and how serious were they?
Unwanted effects are medical problems (such as feeling dizzy) that happen during the study.
• They are described in this summary because the study doctor believes the unwanted effects were related to the treatments in the study.
• Not all of the people in this study had all of the unwanted effects.
• Unwanted effects may be mild to very serious and can be different from person to person.
• It is important to be aware that the unwanted effects reported here are from this single study. Therefore, the unwanted effects shown here may be different from those seen in other studies, or those that appear on the medicine patient information leaflet.
During this study:
• Around 1 in every 4 people (24%) had at least one serious unwanted effect related to pralsetinib • Around 9 out of every 10 people (93%) had an unwanted effect that was related to pralsetinib and not considered serious Question 3: How many people had a positive response to the treatment?
Researchers looked at how well treatment worked in Phase 2 of the study. They looked at the total number of people with RET-altered solid tumours in each group whose disease had either gone away or shrank.
All these people had detectable cancer on tests or scans at the start of the study and were treated with 400mg of pralsetinib once a day.Serious unwanted effects
An unwanted effect is considered 'serious' if it is life-threatening, needs hospital care, or causes lasting problems.
The 6 most common serious unwanted effects across all groups are:
Inflammation of the lung tissue: 26 out of 590 people taking pralsetinib (4%) Lung infection that can cause cough, fever, and difficulty breathinq: 21 out of 590 people taking pralsetinib (4%) Low number of red blood cells: 20 out of 590 people taking pralsetinib (3%) Low level in the blood of a type of white blood cell that helps the body fight infections (neutrophils): 8 out of 590 people taking pralsetinib (1%) Frequent, watery stools: 5 out of 590 people taking pralsetinib (less than 1%) Scarring of the lungs: 5 out of 590 people taking pralsetinib (less than 1%)Out of the 590 people who took part in the study, 9 (2%) died due to unwanted effects that may have been related to the study medicine.
During the study, 58 out of 590 people (10%) decided to stop taking their medicine because of unwanted effects that may have been related to the study medicine.
Most common unwanted effects
The 10 most common unwanted effects across all treatment groups are:
• Higher than usual levels of 'AST' in the blood, which can indicate potential liver, heart or kidney damage (244 out of 590 people taking pralsetinib – 41%)
• Low number of red blood cells (220 out of 590 people taking pralsetinib – 37%)
• Higher than usual levels of 'ALT' in the blood, which can indicate potential liver damage (192 out of 590 people taking pralsetinib – 33%)
• Fewer white blood cells in the body than usual (160 out of 590 people taking pralsetinib – 27%)
• High blood pressure (157 out of 590 people taking pralsetinib – 27%)
• Difficulty pooping (constipation) (151 out of 590 people taking pralsetinib – 26%)
• Low level in the blood of a type of white blood cell that helps the body fight infections (neutrophils) (141 out of 590 people taking pralsetinib – 24%)
• Frequent, watery stools (125 out of 590 people taking pralsetinib – 21%)
• Higher than usual levels of 'creatinine' in the blood, which can indicate potential kidney damage (106 out of 590 people taking pralsetinib – 18%)
• High level of phosphate in the blood (99 out of 590 people taking pralsetinib – 17%)How has this study helped research?
The information presented here is from a single study of 590 people with RET-altered or other solid tumours that have spread. These results helped researchers learn more about these types of cancer and pralsetinib.
The main findings were that:
• The recommended dose of pralsetinib was 400mg once a day
• Overall, people taking pralsetinib were able to continue taking it and function despite having unwanted effects
o Around 24% of people (140 out of 590 people) taking pralsetinib had serious unwanted effects
• A positive response to treatment was seen in:
o 70% of people with RET-fusion non-small cell lung cancer
o 68% of people with RET-mutated thyroid cancer
o 85% of people with RET-fusion thyroid cancer
o 46% of people with other RET-altered solid tumoursYou can find more information about this study on the websites listed below:
• https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3ts%2Fclinicaltrials.gov%252Fct2%252Fshow%252Fresults%252FNCT03037385%2FNBTI%2Fcxq6AQ%2FAQ%2F0d5e8582-3a65-4602-aa52-dd7776216d68%2F1%2FmnLeln9nJ9&data=05%7C02%7Capprovals%40hra.nhs.uk%7Cbab3f08d776b43f77f9c08dd1f723ae0%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638701297647202778%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=6p%2Bw%2BKzqWeueXgEGmJ6TaLiGfO9IoHGjbdD53fAf5tM%3D&reserved=0
• https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3ts%2Fwww.clinicaltrialsregister.eu%252Fctr-search%252Ftrial%252F2016-004390-41%2FNBTI%2Fcxq6AQ%2FAQ%2F0d5e8582-3a65-4602-aa52-dd7776216d68%2F2%2FWqW66rETtC&data=05%7C02%7Capprovals%40hra.nhs.uk%7Cbab3f08d776b43f77f9c08dd1f723ae0%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638701297647218948%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=WjcDJM3QC4MUG2itWVIOmqHEr2942psyZIHE9C%2BYUug%3D&reserved=0 /results
• https:/ /forpatients. roche.com/en/trials/cancer/thyroid-cancer/phase-1-2-study-of-thehighly-selective-ret-inhibitor---95391. htmIWho organised and paid for this study?
This study was organised and paid for by Blueprint Medicines, who have their headquarters in Cambridge, MA, USA, and F. Hoffmann-La Roche Ltd who have their headquarters in Basel, Switzerland.
Full title of the study and other identifying information
The full title of this study is: "A Phase 1/2 Study of the Highly-selective RET Inhibitor, BLU-667, in Patients With Thyroid Cancer, Non-Small Cell Lung Cancer (NSCLC) and Other Advanced Solid Tumors"
The study is known as 'ARROW'.
REC name
West of Scotland REC 1
REC reference
17/WS/0256
Date of REC Opinion
20 Feb 2018
REC opinion
Further Information Favourable Opinion