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
6008 - Quality of life in previously untreated patients with advanced renal cell carcinoma (aRCC) in CheckMate 214: updated results
Presenter: David Cella
Session: Poster Display session 3
Resources:
Abstract
3630 - Results of phase 1 clinical trial of high doses of Seleno-L-methionine (SLM) in sequential combination with Axitinib in previously treated and relapsed clear cell renal carcinoma (ccRCC) patients
Presenter: Yousef Zakharia
Session: Poster Display session 3
Resources:
Abstract
2356 - Safety and Efficacy of CDX-014 , an Antibody-Drug Conjugate against T Cell immunoglobulin mucin-1 (TIM-1), in advanced Renal Cell Carcinoma
Presenter: Bradley McGregor
Session: Poster Display session 3
Resources:
Abstract
1028 - SPAZO2 (SOGUG): Outcomes and prognostic significance of IMDC intermediate prognosis subclassification in metastatic renal cell carcinoma (mRCC) in patients treated with 1st-line pazopanib (1stPz).
Presenter: Begona P. Valderrama
Session: Poster Display session 3
Resources:
Abstract
2293 - Effect of Antacid Intake on the Therapeutic Efficacy of Sunitinib (SUN) in Metastatic Renal Cell Carcinoma (mRCC) Patients (pts): a Sub-Analysis of the STAR-TOR Registry
Presenter: Katrin Schlack
Session: Poster Display session 3
Resources:
Abstract
1451 - Randomized phase 3 trial of avelumab + axitinib vs sunitinib as first-line treatment for advanced renal cell carcinoma: JAVELIN Renal 101 Japanese subgroup analysis
Presenter: Motohide Uemura
Session: Poster Display session 3
Resources:
Abstract
4399 - Overall and progression-free survival according to MSKCC scores in 1st line sunitinib treatment of metastatic renal cell carcinoma (mRCC)
Presenter: Jindrich Finek
Session: Poster Display session 3
Resources:
Abstract
1344 - Combination therapy with checkpoint inhibitors for first-line treatment of advanced renal cell carcinoma: A systematic review and meta-analysis of randomized controlled trials
Presenter: Kyaw Thein
Session: Poster Display session 3
Resources:
Abstract
3462 - A phase II trial of TKI induction followed by a randomized comparison between nivolumab or TKI continuation in renal cell carcinoma (NIVOSWITCH)
Presenter: Viktor Grünwald
Session: Poster Display session 3
Resources:
Abstract
5268 - Nivolumab (N) treatment beyond progression in a real-world cohort of patients (pts) with metastatic renal cell carcinoma (mRCC)
Presenter: Sophie Hans
Session: Poster Display session 3
Resources:
Abstract