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
5760 - Landscape of PD-L1 expression status in Chinese solid tumor patients.
Presenter: Yi Zhong
Session: Poster Display session 3
Resources:
Abstract
3733 - Anti-cancer and immunomodulatory effects of cobimetinib in triple negative breast cancer
Presenter: Chun-Yu Liu
Session: Poster Display session 3
Resources:
Abstract
4426 - Differential expression of immunoregulatory molecules and highly-associated cancer genes may provide novel insights into strategic trial design for therapeutics
Presenter: Jacob Adashek
Session: Poster Display session 3
Resources:
Abstract
2752 - Insights into the Tumor Immune Microenvironment using Tissue Phenomics to Drive Cancer Immunotherapy
Presenter: Martin Groher
Session: Poster Display session 3
Resources:
Abstract
5713 - Immune competent somatic mosaic model of colorectal cancer
Presenter: Stefania Napolitano
Session: Poster Display session 3
Resources:
Abstract
1898 - Genomic correlates of response to anti-PDL1 Atezolizumab in non-small-cell lung cancer OAK and POPLAR trials
Presenter: Hari Singhal
Session: Poster Display session 3
Resources:
Abstract
3246 - Erdafitinib (erda) versus available therapies in advanced urothelial cancer: A matching adjusted indirect comparison
Presenter: Yohann Loriot
Session: Poster Display session 3
Resources:
Abstract
3311 - High level of activity of Nivolumab anti-PD-1 immunotherapy and favorable outcome in metastatic/refractory MSI-H non-colorectal cancer: Results of the MSI cohort from the French AcSé program
Presenter: Christophe Tournigand
Session: Poster Display session 3
Resources:
Abstract
2314 - TP53 and ATM Co-mutation Predicts Response to Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer
Presenter: Yu Chen
Session: Poster Display session 3
Resources:
Abstract
4692 - Immune cell biomarkers on neo-adjuvant chemo-immunotherapy treatment for resectable stage IIIA NSCLC patients
Presenter: Raquel Laza-Briviesca
Session: Poster Display session 3
Resources:
Abstract