Translational Subcommittee
ANNUAL
REPORT 2024
Translational Subcommittee
ANNUAL
REPORT 2024
ANNUAL REPORT 2024
Translational Subcommittee
Translational Subcommittee
Arun azad
CHAIR
Anthony Joshua
DEPUTY CHAIR
Over the past year, the Translational Research Subcommittee (TRS) has been highly productive with several subcommittee meetings held.
ANZUP remains committed to making translational research a cornerstone of the organisation’s mission, and the TRS has been instrumental in facilitating this goal by leading translational research activities for ANZUP-led trials.
ANZUP Trials – Translational Research Activity Plan
Renal Cell Cancer (RCC)
KEYPAD (ANZUP1601)
ANZUP is collaborating with MSD and AMGEN to perform TR sub studies for KEYPAD. Biospecimens collected from the KEYPAD trial are now centralized at the Hunter Cancer Biobank. Translational research (TR) sub-studies are currently planned to determine the potential of RANKL inhibition in reducing tumor immuno-suppression and increasing the effectiveness of anti-PD1 immunotherapy.
UNICAB (ANZUP1802)
Shipment is currently in progress from various sites to the central repository for UNICAB TR. ANZUP has secured the Perpetual Impact Philanthropy grant 2024 to support a TR study for UNICAB.
UNISON (ANZUP 1602)
Reconciliation of TR biospecimens are currently being carried out at the central repository. The TR sub-studies currently planned for UNISON are funded through the Perpetual Impact Philanthropy grant. UNISON biospecimens will be processed together with KEYPAD samples to investigate the association between clinical outcomes and immune related biomarkers in renal cancer.
Bladder Urothelial Penile (BUP)
PCR-MIB (ANZUP 1502)
In collaboration with Merck, the PCR-MIB TR project team is working on RNA spatial transcriptomics. The team has developed a custom CosMx panel to investigate the spatial transcriptomics of tertiary lymphoid structures. Tumor blocks will be requested from PCR-MIB trial sites in early July for complex RNA spatial transcriptomics (done at the Merck USA site) and multiplex IHC (done at Olivia Newton-John Cancer Centre). Single cell RNA analysis of circulating sorted immune cells will then be performed using patient blood and the results obtained will be correlated with matched spatial transcriptomic data.
BCC+MM (ANZUP 1301)
A TR sub-study is currently planned for BCGMM trial to identify histologic biomarkers and to determine its potential clinical utility using AI-machine learning tool developed by Valar Labs, USA. The tool has been trained to identify histologic features extracted from digital whole slide images of hematoxylin and eosin (H&E)-stained specimens.
Germ Cell Carcinoma (GCC)
TIGER (ANZUP 1604)
Samples collected from the TIGER trial are awaiting shipment to the Alliance Biorepository in the US. Pharmacogenomic and tumor biology-related correlative studies will be conducted by Alliance using whole blood and tumor tissue samples
CLIMATE (ANZUP 1906)
Sample collection for TR is ongoing, with the aim of developing a miRNA-based assay for minimal residual disease (MRD) analysis in testicular germ cell tumors. Pilot studies are currently underway to determine the sensitivity and specificity of the miRNA assay.
P3BEP (ANZUP 1302)
An NHMRC grant was successful and secured an additional 5 years of funding to complete this clinical trial. TR work will be delayed until the trial completes accrual.
Prostate Cancer (PC)
ENZA-p (ANZUP 1901)
Analysis of circulating tumor cells (CTCs) in ENZAP blood samples is underway in collaboration with EPIC Sciences. Additional TR sub-studies focusing on ctDNA and lipids in ENZAP plasma samples are planned and at the contract stage.
ENZAMET (ANZUP 1304)
ENZAMET TR is an extensive program currently involving 14 TR sub-studies. These studies focus on genomic, transcriptomic, metabolomic, proteomic, and AI-machine learning approaches to identify biomarkers of predictive and prognostic significance in ENZAMET patients. All studies are in progress: some are completed, others are underway at various stages of sample shipment, biomarker data generation, correlative analysis, etc. The University of Adelaide has now established a data use agreement with ANZUP and may potentially create an ANZUP data repository for ENZAMET in the future. The ANZUP International Trial Steering Committee (ITSC) met at ASCO in June 2024 to discuss the progress of ENZAMET TR.
ENZARAD (ANZUP 1303)
A TR program is currently being developed for ENZARAD. The initial plans for this program involve conducting whole exome sequencing (WES) and gene expression profiling (GEP) on ENZARAD tissue samples, likely in collaboration with industry partners. Once the proposal has been reviewed internally, it will be presented at the next International TR Committee meeting for further evaluation and approval.
TheraP (ANZUP 1603)
Using longitudinal liquid biopsy (plasma) biospecimens collected from the TheraP trial, the TR project team at the Vancouver Prostate Centre (VPC) has identified ctDNA fraction as a prognostic and predictive biomarker in patients treated with Lu-PSMA. Dr. Edmond Kwan presented this work at ASCO 2024 and was awarded the prestigious Conquer Cancer Foundation Merit Award. Another project currently in progress under the TheraP TR program include the analysis of circulating lipids as cancer biomarkers. Furthermore, the Australian Prostate Cancer Research Centre (APCRC) in Queensland has shown interest in collaborating with ANZUP on proteomic and lipidomic studies using TheraP TR biospecimens.
EVOLUTION (ANZUP 2001)
The biospecimens collected as part of the EVOLUTION trial have been sent to the central laboratory. Funding proposals to industry partners to support TR sub-studies, including ctDNA analysis, single-cell transcriptomics, and other related research activities, have been submitted, with partial funding secured. There are also plans to submit a grant proposal to the US Department of Defense (DoD) next year.
DASL-HiCAP (ANZUP 1801)
A preliminary TR work plan has been submitted for consideration for funding by industry partners. The work plan includes gene expression profiling (GEP) and whole exome sequencing (WES) of tumor tissue, with a larger program of TR sub-studies currently under development.