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
3290 - Identification of meningioma patients in high risk of tumor recurrence using microRNA profiling
Presenter: Josef Srovnal
Session: Poster Display session 3
Resources:
Abstract
2477 - Antecedent of cancer and mortality after the first ST segment elevation acute myocardial infarction treated with primary coronary angioplasty. A prospective cohort study
Presenter: Irene Sillero
Session: Poster Display session 3
Resources:
Abstract
1894 - Genomic characterisation of locally advanced pancreatic adenocarcinoma
Presenter: Sarah Picardo
Session: Poster Display session 3
Resources:
Abstract
3280 - Comparison of freshly prepared and frozen cells from colorectal cancer surgical samples for phenotyping experiments- a pilot study
Presenter: Sandra Mersakova
Session: Poster Display session 3
Resources:
Abstract
3419 - Hyaluronan (HA) Accumulation in the Tumor Microenvironment (TME) is Increased in Colorectal Cancer (CRC) and Associated with Consensus Molecular Subtypes (CMS) 4 Molecular Subtype
Presenter: Barbara Blouw
Session: Poster Display session 3
Resources:
Abstract
1833 - Evaluation of CT-based radiomics in patients with renal cell carcinoma
Presenter: An Zhao
Session: Poster Display session 3
Resources:
Abstract
5883 - Detection of Double Protein Expression in Diffuse Large B Cell Lymphoma
Presenter: Mohamed Gouda
Session: Poster Display session 3
Resources:
Abstract
5415 - Encyclopedic Tumor Analysis for organ agnostic treatment with Axitinib in combination regimens for advanced cancers
Presenter: Tim Crook
Session: Poster Display session 3
Resources:
Abstract
3297 - Computational model to predict response rate of clinical trials
Presenter: Orsolya Lorincz
Session: Poster Display session 3
Resources:
Abstract
4355 - Analysis of BRCA genes and homologous recombination deficiency (HRD) scores in tumours from patients (pts) with metastatic breast cancer (mBC) in the OlympiAD trial
Presenter: Mark Robson
Session: Poster Display session 3
Resources:
Abstract