First in human study of T3P-Y058-739 (T3P)
Research type
Research Study
Full title
An open-label, phase I/II study of T3P-Y058-739, a genetically-modified strain of the bacterium Yersinia enterocolitica, in patients with advanced solid tumors
IRAS ID
1003337
Contact name
Kevin Harrington
Contact email
Sponsor organisation
T3 Pharmaceuticals AG
Eudract number
2020-002645-42
Research summary
T3P is a live attenuated bacterium that has been modified to remove pathogenicity and to enable the bacterium to micro-inject surrounding human cells and to stimulate the production of type I interferons and other cytokines which attract and activate cells of the immune system. Microinjection by T3P takes place via the naturally occurring bacterial type 3 secretion system (T3SS). The T3SS looks and acts like minute syringes (sometimes called nano-syringes or injectisomes) on the surface of the bacteria. Microinjection of cargo proteins may occur very rapidly (within minutes) of T3P being introduced into a tumour by local intra-tumoural (IT) injection. It can also occur more slowly, as tumours become colonised by T3P following intravenous (IV) administration.
In addition to delivery of the cargo proteins via the T3SS, the T3P bacteria themselves stimulate the production of potent pro-inflammatory cytokines. Thus, the presence of T3P in tumours is anticipated to result in stimulation of a strong immune response to the tumour.
The study will be conducted in patients with advanced solid tumours. It has a modular design with up to 6 parts. Part A will open first. Parts B and subsequent parts will open later. Each of the 6 modules can be opened and closed independently and results can be published separately. Part A involves local injection of T3P into the tumour; Part B involves intravenous administration; and Part C involves administration of T3P (by intratumoural injection or intravenous infusion – to be decided) in combination with pembrolizumab. Parts D, E and F are phase II extensions to evaluate the regimens in patients with selected tumour types. Details of these parts of the study will be decided based on emerging data. The protocol will be amended to include these details before these parts of the study can open.
The number of patients enrolled in the study depends on how many dose levels are needed to define the recommended phase II dose (RP2D) in Parts A, B and/or C, and how many parts of the study open. However, it is estimated that the total sample size for the study will be between 67 and 100 patients.REC name
North East - York Research Ethics Committee
REC reference
21/NE/0006
Date of REC Opinion
8 Mar 2021
REC opinion
Further Information Favourable Opinion