Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2018

Molecular determinants of autoimmunity and immune related adverse eventsĀ in advanced cancer patients treated with immune checkpoint inhibitors (AUTO-CHECK study) (#318)

Anna K Nowak 1 , Sonia Yip 2 , Martin Stockler 2 , Desmond Yip 3 , Paul Mitchell 4 , Yoland Antill 5 , Daniel Andrews 3 , Chee Lee 2 , Craig Gedeye 6 , Mustafa Khasraw 2 , Kristy Robledo 2 , Michelle Parry 2 , Carola Vinuesa 7 , Sayed Ali 8 , Willem J Lesterhuis 1 , Matthew Cook 3
  1. University of Western Australia, Perth, WA, Australia
  2. NHMRC Clinical Trials Centre, Sydney
  3. Australian National University, Canberra
  4. Austin Hospital, Melbourne
  5. Cabrini Health, Melbourne
  6. Calvary Mater Newcastle Hospital, Newcastle
  7. John Curtin School of Medical Research, Canberra
  8. St John of God Midland, Perth

Aim The general aim of this study is to determine the genetic and cellular bases of susceptibility to autoimmune adverse effects in patients receiving immune checkpoint inhibitors (ICIs).

Objectives The specific objectives are to determine:

  1. baseline molecular predictors of immune-related adverse events (IRAEs),
  2. common and rare genetic variants that segregate with IRAEs, and
  3. changes in lymphocytes (effector, memory and regulatory subsets), and the kinetics and distribution of CTLA4 and PD-1 expression in patients with or without IRAEs.

Methods Additional biospecimens and data are being collected in 6 investigator-initiated, multicentre clinical trials of ICIs, and 1 single-site observational study.

Included trials spanning multiple tumour types: endometrial cancer (PHAEDRA), renal cell cancer (KEYPAD), mesothelioma (DREAM), non-small-cell lung cancer (NIVORAD, ILLUMINATE), glioblastoma multiforme (NUTMEG), and mixed cancer types treated with ICI at Canberra Hospital (CH). Blood samples are shipped in real-time from sites to the central laboratory at Australian National University for isolation of peripheral blood mononuclear cells. Frozen whole blood and serum samples are also collected.

Study blood timepoints are at baseline, 4-12 weeks after commencing ICI, and at time of any IRAE.

Accrual since June 2017: DREAM: 35, PHAEDRA: 44, KEYPAD: 9, NIVORAD: 9, NUTMEG: 5, ILLUMINATE: 0, CH cohort: 18; for a total of 120 out of 300 planned participants (40%).