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.
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