ASP8374 alone and with pembrolizumab for advanced solid tumours
Research type
Research Study
Full title
A Phase 1b Study of ASP8374, an Immune Checkpoint Inhibitor, as a Single Agent and in Combination with Pembrolizumab in Subjects with Advanced Solid Tumors
IRAS ID
251868
Contact name
Johann de Bono
Contact email
Sponsor organisation
Astellas Pharma Global Development, Inc
Eudract number
2018-001146-34
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
131050, IND
Duration of Study in the UK
3 years, 6 months, 21 days
Research summary
Summary of Research
The purpose of this study is to test a new drug (ASP8374) in patients with advanced solid tumours that cannot be removed by surgery or may have spread to other parts of the body. ASP8374 will be given either alone or combined with pembrolizumab. The study aims to determine at what dose ASP8374 is safe and tolerated and how it is processed in the body. Once an acceptable dose has been identified, ASP8374 will be assessed to see if it causes tumours to shrink.
This is the first time that ASP8374 will be given to humans. ASP8374 targets the TIGIT receptor which is found on some cells of the immune system. TIGIT acts to turn off the immune system after it has been activated by inhibiting the TIGIT receptor. ASP8374 may help the immune system to attack tumour cells.
Patients will be assigned to a dose of between 0.5mg and 1400mg ASP8374 based on available dose levels at the time of study entry. They will be randomly allocated to receive either ASP8374 alone or in combination with pembrolizumab.
The study consists of a 28-day screening period, 48-week initial treatment period and a 45-week follow-up period. Patients may receive an additional 48-weeks re-treatment if applicable. ASP8374 and pembrolizumab (if applicable) will be given through a vein on Day 1 of each 21 day cycle. Patients will visit the hospital 3 times during the first 2 cycles and twice during subsequent cycles. Follow-up visits will take place 30 and 90 days after the last dose and then every 9 weeks from the last scan. Study procedures include vital signs, physical examination, blood testing and CT/MRI scans.
The study is sponsored by Astellas Pharma Global Development. Approximately 363 patients will participate worldwide with 25 patients from 5 hospitals in the UK.
Summary of Results
What is the most suitable dose of ASP8374?
This question was answered by firstly checking how ASP8374 is processed by the body. Blood samples were taken at certain times throughout treatment to check how much ASP8374 is in the blood over time. This helps to provide information on how ASP8374 moves through the body, and so builds up a picture of how ASP8374 is processed by the body. From this, the most suitable dose can be worked out. The information shown here is for treatment with ASP8374 by itself and together with pembrolizumab.
The overall amount of ASP8374 in the blood was higher after each increased dose. It was also higher for the same dose when it was repeated. However, the researchers could not conclude anything as too many people stopped taking ASP8374 early.
This meant that the most suitable dose of ASP8374 could not be worked out.
Did people’s tumors shrink after treatment with ASP8374 by itself or together with pembrolizumab?
Early data showed that tumors did not shrink after study treatment. This was why the study was stopped early.
You can find more information about this study at the websites listed below.
https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.gov%2F&data=05%7C01%7Capprovals%40hra.nhs.uk%7Cba49f29f7d744fcdb6b508db351bb2ae%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638162165294598568%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=oPPoOh2aS0OBy67aWp9v2A%2F6%2FAP62Ca%2F4St66yo5SaI%3D&reserved=0 and searching for the number NCT03260322
https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.astellas.com%2F&data=05%7C01%7Capprovals%40hra.nhs.uk%7Cba49f29f7d744fcdb6b508db351bb2ae%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638162165294598568%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=NJ7vfjPNdbDjZuQKGxKgVTS8D4OC65GOwIU9f6r%2B%2F2E%3D&reserved=0REC name
London - Chelsea Research Ethics Committee
REC reference
19/LO/0124
Date of REC Opinion
24 Apr 2019
REC opinion
Further Information Favourable Opinion