Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Display session 3

1645 - PRIME002 - Early phase II study of Azacitidine and Carboplatin priming for Avelumab in patients with advanced melanoma who are resistant to immunotherapy

Date

30 Sep 2019

Session

Poster Display session 3

Presenters

Andre Van Der Westhuizen

Citation

Annals of Oncology (2019) 30 (suppl_5): v533-v563. 10.1093/annonc/mdz255

Authors

A. Van Der Westhuizen1, M. Graves2, R. Levy1, A. Majid1, R. Vilain3, N. Bowden2

Author affiliations

  • 1 Medical Oncology, Calvary Mater Hospital Newcastle, 2298 - Newcastle/AU
  • 2 School Of Medicine And Public Health, University of Newcastle, Callaghan/AU
  • 3 Anatomical Pathology, John Hunter Hospital, 2305 - Newcastle/AU
More

Resources

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.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings