Abstract 1645
Background
Melanoma patients with disease progression on immunotherapy have very limited treatment options. Low-dose azacitidine results in demethylation and increase in neoantigen expression and carboplatin increases DNA-damage and cellular stress. This trial is testing if sequential treatment with azacitidine and carboplatin “primes” for immunotherapy rechallenge with anti-PDL1 antibody Avelumab, via a decrease in the disease burden and re-establishment of immune sensitivity. Primary Objective: Quantify complete response (CR), partial response (PR), stable disease (SD), overall response rate (ORR) and clinical benefit rate (CBR) after 2 cycles of priming (1 cycle= azacitidine x 5 days followed by Carboplatin Day 8/28 days) according to RECIST 1.1 and 6 cycles of immunotherapy (1 cycle= 1 dose of Avelumab/14 days) according to irRECIST criteria. Secondary Objectives: 1. Determine DNA methylation levels before, and immediately after priming with azacitidine and carboplatin treatment i.e. at study entry and after 2 months; 2. Quantify immune-response markers (PDL-1, PD-1, CD4/CD8, and CD68) in blood, tumour and microenvironment and immune response in blood before treatment, after 2 priming cycles and after 6 immunotherapy cycles.
Trial design
Interventional early phase II study that consists of 2 cycles of azacitidine 40mg/m2 IV/day for 5 days followed by Carboplatin AUC 4.5 IV on D8/ 28 day cycle and RECIST1.1 after completion of priming; followed by Avelumab 10mg/kg IV/14 day cycle until disease progression according to irRECIST. A favourable or stable response in 20% patients and no grade 4 or persistent (>4 weeks) grade 3 treatment-related adverse events (TRAEs) is required for continuation of the trial. This early phase II study will assess the feasibility and determine outcome measures required to calculate sample sizes and develop a statistical plan for multi-centre Phase II study. This study has been approved by the Northern Sydney Local Health District HREC, reference number HREC/17/HAWKE/55’.
Clinical trial identification
ACTRN12618000053224; registered 16th January 2018.
Editorial acknowledgement
Legal entity responsible for the study
Andre van der Westhuizen.
Funding
Ramaciotti Foundation and Hunter Medical Research Institute, Australia.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
2963 - Analytical performance of the Resolution-HRD plasma assay used to identify mCRPC patients with biallelic disruption of DNA repair genes for treatment with niraparib
Presenter: Ira Pekker
Session: Poster Display session 3
Resources:
Abstract
3523 - Results of a global external quality assessment scheme for EGFR testing on liquid biopsy
Presenter: Nicola Normanno
Session: Poster Display session 3
Resources:
Abstract
3295 - Clinical impact of plasma Next-Generation Sequencing (NGS) in advanced Non-small cell lung cancer (aNSCLC)
Presenter: Laura Bonanno
Session: Poster Display session 3
Resources:
Abstract
5632 - Feasibility study of a ctEGFR prototype assay on the fully automated Idylla™ platform
Presenter: Martin Reijans
Session: Poster Display session 3
Resources:
Abstract
3614 - Enhanced Access to EGFR Molecular Testing in NSCLC using a Cell-Free DNA Tube for Liquid Biopsy
Presenter: Theresa May
Session: Poster Display session 3
Resources:
Abstract
5664 - Analysis of circulating tumor DNA in paired plasma and sputum samples of EGFR-mutated NSCLC patients
Presenter: Christina Grech
Session: Poster Display session 3
Resources:
Abstract
4945 - Liquid biopsy and Array Comparative Genomic Hybridization (aCGH)
Presenter: Panagiotis Apostolou
Session: Poster Display session 3
Resources:
Abstract
5746 - Next-generation sequencing panel verification to detect low frequency single nucleotide and copy number variants from mixing cell line studies
Presenter: Rocio Rosas-Alonso
Session: Poster Display session 3
Resources:
Abstract
5901 - Automated rarefaction analysis for precision B and T cell receptor repertoire profiling from peripheral blood and FFPE-preserved tumor
Presenter: Luca Quagliata
Session: Poster Display session 3
Resources:
Abstract
2027 - A Heptamethine cyanine dye is a potential diagnostic marker for Myeloid-Derived Suppressor Cells
Presenter: Chaeyong Jung
Session: Poster Display session 3
Resources:
Abstract