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
3252 - Genes involved in DNA replication, chromatin remodeling and cell cycle as potential biomarkers for therapy outcome to immune therapy in patients with metastatic cutaneous malignant melanoma
Presenter: Fernanda Costa Svedman
Session: Poster Display session 3
Resources:
Abstract
5545 - Phase Ib/II Study (SENSITIZE) assessing safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical outcome of domatinostat in combination with pembrolizumab in patients with advanced melanoma refractory/non-responding to prior checkpoint inhibitor therapy
Presenter: Jessica Hassel
Session: Poster Display session 3
Resources:
Abstract
5213 - Genomic landscape of primary malignant melanoma of esophagus
Presenter: Jie Dai
Session: Poster Display session 3
Resources:
Abstract
2716 - A phase III, randomised, double-blind study of adjuvant cemiplimab versus placebo post-surgery and radiation in patients with high-risk cutaneous squamous cell carcinoma (CSCC)
Presenter: Danny Rischin
Session: Poster Display session 3
Resources:
Abstract
3550 - ILLUMINATE 301: A randomized phase 3 study of tilsotolimod in combination with ipilimumab compared with ipilimumab alone in patients with advanced melanoma following progression on or after anti-PD-1 therapy
Presenter: Marcus Butler
Session: Poster Display session 3
Resources:
Abstract
1645 - PRIME002 - Early phase II study of Azacitidine and Carboplatin priming for Avelumab in patients with advanced melanoma who are resistant to immunotherapy
Presenter: Andre Van Der Westhuizen
Session: Poster Display session 3
Resources:
Abstract
4440 - Pembrolizumab (pembro) Plus Lenvatinib (len) for First-Line Treatment of patients (pts) With Advanced Melanoma: Phase 3 LEAP-003 Study
Presenter: Alexander Eggermont
Session: Poster Display session 3
Resources:
Abstract
3454 - Proof of concept study with the histone deacetylase inhibitor vorinostat in patients with resistant BRAFV600 mutated advanced melanoma
Presenter: Sanne Huijberts
Session: Poster Display session 3
Resources:
Abstract
1832 - A phase Ia/Ib clinical study to evaluate the safety, pharmacokinetics (PK) and preliminary anti-tumor activity of FCN-159 in patients with advanced melanoma harboring NRAS-aberrant (Ia) and NRAS-mutation (Ib).
Presenter: Lu Si
Session: Poster Display session 3
Resources:
Abstract
3996 - A Phase I Clinical Trial Investigating the Therapeutic Cancer Vaccine UV1 in Combination with Pembrolizumab as First-Line Treatment of Patients with Malignant Melanoma
Presenter: Sanjiv Agarwala
Session: Poster Display session 3
Resources:
Abstract