Abstract 974TiP
Background
Tigilanol tiglate is a novel, short-chain diterpene ester, in clinical development for local treatment of solid tumours. It acts by targeting specific isoforms of protein kinase C leading to (i) rapid, localized, inflammation, (ii) increased permeability of tumour vascular endothelium, and (iii) rapid tumour oncosis and destruction within 4 - 14 days. In addition, the tumour deficit site heals without interventions. In a previous phase I study (22 patients), intratumoural injection was well tolerated (96% of adverse events were mild to moderate), clinical activity (three patients with complete response and three with partial response) was observed in nine tumour types, with anenestic tumour responses in two patients (Panizza et al., 2019).
Trial design
This is a phase Ib/IIa, multi-centre, dose-escalation study of intratumoural tigilanol tiglate in up to 40 patients with head and neck squamous cell carcinoma. Key eligibility criteria include: ECOG (0-2), adequate organ function and tumour accessibility. Endpoints include: safety parameters, MTD, PK and tumour response assessments. The primary objective is the safety and tolerability of tigilanol tiglate as a single dose. Secondary objectives are safety and tolerability of up to two repeat doses, determination of MTD, tumour response (RECIST / WHO criteria), PK and exploratory PD. Tigilanol tiglate is administered at 0.5 mL / 1.0 cm3 tumour, with escalating doses based on body surface area (from 1.2 mg/m2), subject to data safety monitoring board review. Patients are grouped by target tumour size (0.1 - ∼4 cm3 or ∼4 - 50 cm3). Stage 1: Single dose of tigilanol tiglate, observed on Days 1, 3, 7, 14 until (i) Day 21; (ii) commencement of Stage 2, (iii) scheduled surgery between Days 14 - 21, or (iv) start of standard of care. Stage 2: Tigilanol tiglate may be re-administered two more times at the same dose level to any remaining treated tumour, 21 days after the first treatment, at least one week apart. Tumour biopsies and CT scans are performed pre- and post-treatment. The study commenced in November 2019, with four patients enrolled at the time of this submission.
Clinical trial identification
Protocol number: QB46C-H03; Clinical Trial Registries: ACTRN12619001407189 / CTRI/2019/11/022032.
Editorial acknowledgement
Legal entity responsible for the study
QBiotics Group Limited (ACN: 617 596 139).
Funding
QBiotics Group Limited.
Disclosure
A. Pattatheyil, R. Sharan: Honoraria (institution): QBiotics Group Limited. B.J. Panizza: Advisory/Consultancy, Travel/Accommodation/Expenses: QBiotics Group Limited. D.J. Swart: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: QBiotics Group Limited. T.L. Mynott: Full/Part-time employment: QBiotics Group Limited. A. Cleal: Advisory/Consultancy, Travel/Accommodation/Expenses: QBiotics Group Limited. V. Gordon: Leadership role, Research grant/Funding (institution), Shareholder/Stockholder/Stock options, Full/Part-time employment, Officer/Board of Directors: QBiotics Group Limited. A. Prawira: Research grant/Funding (institution), Funding from QBiotics Group to institution to conduct clinical trials.: QBiotics Group Limited; Advisory/Consultancy, Non-remunerated advisory role to QBiotics Group.: QBiotics Group Limited. All other authors have declared no conflicts of interest.