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
5705 - External validation and longitudinal extension of the LIPI (Lung Immune Prognostic Index) for immunotherapy outcomes in advanced non-small cell lung cancer.
Presenter: Jakob Riedl
Session: Poster Display session 3
Resources:
Abstract
5758 - Changes of TCR Repertoire in Metastatic Renal Cell Carcinoma and Metastatic Melanoma Patients Treated with Nivolumab
Presenter: Martin Klabusay
Session: Poster Display session 3
Resources:
Abstract
1743 - Expression of MHC class I, HLA-A and HLA-B identifies immune activated breast tumors with favorable outcome
Presenter: María Del Mar Noblejas López
Session: Poster Display session 3
Resources:
Abstract
2219 - Prognostic Significance of Tumor Tissue NeuGcGM3 Ganglioside Expression and Predictive Value of Circulating Tumor Cell Count Monitoring in Patients Receiving Racotumomab Immunotherapy
Presenter: Necdet Üskent
Session: Poster Display session 3
Resources:
Abstract
2996 - Evolution of Myeloid-Derived Suppressor Cells and Objective Response Rate in Relapsed/Refractory Diffuse Large B Cell Lymphoma (R/R DLBCL) patients after receiving immunotherapy
Presenter: Carlos Jiménez Cortegana
Session: Poster Display session 3
Resources:
Abstract
2110 - A Phase Ia/Ib trial of the anti-programmed death-ligand 1 (PD-L1) human monoclonal antibody (mAb), CS1001, in patients (pts) with advanced solid tumors or lymphomas
Presenter: Lin Shen
Session: Poster Display session 3
Resources:
Abstract
3515 - Results from a randomised Phase 1/2 trial evaluating the safety and antitumour activity of anti-PD-1 (MEDI0680)/anti-PD-L1 (durvalumab) vs anti-PD-1 (nivolumab) alone in metastatic clear cell renal cell carcinoma (ccRCC)
Presenter: Martin Voss
Session: Poster Display session 3
Resources:
Abstract
3566 - Pembrolizumab in Advanced Rare Cancers
Presenter: Aung Naing
Session: Poster Display session 3
Resources:
Abstract
3567 - High clinical benefit rates of pembrolizumab in very rare sarcoma histotypes: first results of the AcSé Pembrolizumab study
Presenter: Jean-Yves Blay
Session: Poster Display session 3
Resources:
Abstract
2421 - Lenvatinib plus PD-1 blockade in advanced bile tract carcinoma.
Presenter: Jianzhen Lin
Session: Poster Display session 3
Resources:
Abstract