1. ARACHNID Trial Development and Radiotherapy/Immune-oncology Combination Expertise and Capability
The Liverpool ECMC is leading and co-ordinating the ARACHNID phase II, multi-arm, adaptive trial of durvalumab and tremelimumab in combination with different radiotherapy modalities for advanced hepatocellular carcinoma (Chief Investigator: Prof Daniel Palmer, Liverpool ECMC Lead).
This trial, which is only the second academic proton study, has been developed in collaboration with colleagues from across the ECMC Network: Prof Maria Hawkins (Co-CI & Radiotherapy Lead - Oxford), Prof Tim Meyer (Co-Investigator – UCL) and Dr Ganesh Radhakrishna (Proton Lead – Manchester).
This trial provides a unique opportunity to assess the combination of checkpoint inhibitors with stereotactic body radiation therapy (SBRT) and also β-particle brachytherapy & protons to determine how different radiotherapy modalities may influence immune responses.
ECMC support has been crucial in development of this trial. In Liverpool, ECMC funded staff have designed the trial and developed the clinical and translational protocol and will continue to support the set-up and delivery of this trial.
This trial adds to the increasing portfolio of radiotherapy/immune-oncology combination trials led by Liverpool (NICO, RADIANT-BC) and is underpinned by local translational and pre-clinical research in the radiotherapy and radiobiology fields.
Bio-samples collected as part of this portfolio will be available to the ECMC Network.
2. Development of hENT1 as an IHC Biomarker
A key aspect of our translational research programme is identifying therapeutic biomarkers for use in the clinical management of cancer. There are currently no predictive biomarkers available to guide treatment of pancreatic ductal adenocarcinoma (PDAC), a disease with a notoriously poor prognosis.
We have previously shown that tumour equilibrative nucleoside transporter 1 (hENT1) levels predict response to adjuvant gemcitabine in PDAC, using samples from a large phase 3 randomised clinical trial, ESPAC-3. Work is currently underway examining if the predicted poor response to gemcitabine conferred by low levels of intratumoural hENT1 can be overcome by combination with capecitabine, utilising samples from the ESPAC-4 study.
To test if hENT1 may have utility in the advanced setting, analysis is also currently ongoing of hENT1 levels in core biopsies from locally advanced primary tumour and distant metastases, as part of the ACELERATE randomised clinical trial.
By examining hENT1 alongside other potential biomarkers associated with chemotherapy uptake and metabolism, we aim to generate a panel of candidates for guiding therapy based on tumour molecular profiles.