Abstract 3010
Background
Analysis of outliers leads to breakthroughs in oncology. Examples of this include pan-approval for anti-PD1 therapy in mismatch repair deficient tumours and TSC1 as a biomarker for mTOR inhibitor response. We aim to recruit patients with an exceptional response to anti-cancer therapy and analyse tumour and normal tissue for genomic changes predisposing to this response. We are collaborating with similar programs internationally to enable cross-comparison. Genomic data with non-identifying clinical data will be included in a controlled-access online repository.
Trial design
The program is promoted through national professional organisations and trials groups. Patients are consented via Telehealth after referral by their treating clinician. Relevant clinical records are obtained and considered by a tumour-specific sub-committee. An exceptional response is defined as complete (CR) or partial response (PR) where <10% would be expected to respond, CR or PR lasting > 3 times that expected, or best response progressive disease where >90% of patients would be expected to respond. Consideration is given to the broader context of each case, and exceptional cases that do not meet these criteria. Once approved, patients are contacted to provide a once-off blood sample at their local pathology unit. Blood is couriered to the Garvan Institute, an aliquot removed for DNA extraction, and the remainder processed into PBMC and non-lymphocyte fractions. DNA is analysed for germline variants using whole genome sequencing (Illumina HiSeqX Ten). Archival tissue is retrieved for analysis at St Vincent’s SydPath. Tumour analysis includes histological confirmation of diagnosis, tumour proportion score, degree of necrosis and ancillary tests as appropriate. DNA and RNA is extracted from tumour tissue and analysed using a targeted panel with select analysis of copy number variants and gene fusions (Oncomine Comprehensive Assay v3.0). Further analysis is determined by quantity and quality of available tissue. To date, thirty-eight patients have been recruited across twelve tumour types. Emerging sub-groups include pancreas adenocarcinoma (n = 5), prostate (n = 5), non-small cell lung cancer (n = 5) and malignant pleural mesothelioma (n = 4).
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Garvan Institute of Medical Research.
Funding
Kinghorn Foundation and Bioplatforms Australia.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
4900 - Molecular profiling and prognostic significance of TP53 mutations in Diffuse Large B Cell Lymphoma: identifying a high-risk subgroup
Presenter: Yuan-Kai Shi
Session: Poster Display session 3
Resources:
Abstract
3809 - Differential expression of various miRNAs in Pediatric Cytogenetically Normal Acute Myeloid Leukemia (CN-AML)
Presenter: Vikas Gaur
Session: Poster Display session 3
Resources:
Abstract
4750 - Circulating tumour cells in head and neck and non-small cell lung cancer
Presenter: Kenneth O'Byrne
Session: Poster Display session 3
Resources:
Abstract
3704 - OX40/OX40L protein expression in Non-small cell lung cancer and its role in clinical outcome and relationships with other immune biomarkers
Presenter: Xiaoshen Zhang
Session: Poster Display session 3
Resources:
Abstract
2235 - Effect of Serum Survivin on Survival among Non-Small Cell Lung Cancer Patients; NCI Experience
Presenter: Reham Rashed
Session: Poster Display session 3
Resources:
Abstract
2788 - Enhanced performance of prognostic estimation from TCGA RNAseq data using transfer learning.
Presenter: Helene Vanacker
Session: Poster Display session 3
Resources:
Abstract
4689 - Analysis of Circulating Tumor DNA for Early Relapse Detection in Stage III Colorectal Cancer After Adjuvant Chemotherapy
Presenter: Samuel Jacobs
Session: Poster Display session 3
Resources:
Abstract
1454 - Ascites-derived circulating microRNAs as potential diagnostic biomarkers of gastric cancer-associated malignant ascites
Presenter: Hye Sook Han
Session: Poster Display session 3
Resources:
Abstract
5574 - Results from TRIO030, a Pre-Surgical Tissue-Acquisition Study to Evaluate Molecular Alterations in Human Breast Cancer Tissue Following Short-Term Exposure to the Androgen Receptor Antagonist Darolutamide
Presenter: Hsiao-Wang Chen
Session: Poster Display session 3
Resources:
Abstract
1787 - JMJD2A is a novel epigenetic factor of chemotherapeutic susceptibility in gastric cancer
Presenter: Yasushi Sato
Session: Poster Display session 3
Resources:
Abstract