Poster Presentation 35th Lorne Cancer Conference 2023

Why are they responding? Using immuno-genomics to understand combination PARP inhibitor plus immunotherapy response in high-grade serous ovarian cancer: SOLACE2 (#116)

Nirashaa T Bound 1 2 , Cassandra Vandenberg 1 3 , Kristy Shield-Artin 1 , Justin Bedo 1 , Jocelyn Penington 1 , Imalki Kariyawasam 1 , Ramyar Molania 1 , April Kartikasari 2 , Momodou Cox 2 , Gayanie Ratnayake 4 , Chee Lee 5 6 7 , Michael Friedlander 7 8 , Matthew Wakefield 1 , Tony Papenfuss 1 9 , Magdalena Plebanski 2 , Clare Scott 1 3 4 7 9 10
  1. The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
  2. Cancer Ageing and Vaccines (CAVA), Translational Immunology and Nanotechnology Program, RMIT university, Melbourne, VIC, Australia
  3. Melbourne University , Parkville, VIC, Australia
  4. Royal women's hospital, Parkville, VIC , Australia
  5. St George Hospital, Sydney, NSW, Australia
  6. National Health and Medical Research Council (NHMRC) Clinical Trials Centre, Sydney, NSW, Australia
  7. Australia New Zealand Gynaelogical Oncology Group (ANZGOG), Camperdown, NSW, Australia
  8. Sydney and Prince of Wales Clinical School, University of New South Wales, Prince of Wales Hospital, Sydney, NSW, Australia
  9. Peter MacCallum Cancer center, Melbourne, VIC, Australia
  10. The Royal Melbourne Hospital, Melboune, VIC, Australia

Current first-line treatments for high grade serous ovarian carcinoma (HGSOC) combining cytoreductive surgery with platinum-taxane-based chemotherapy only enable 30% of women responding to remain in remission, with the remainder relapsing within 4-16 months (mo) with progressively more chemo-resistant disease. SOLACE2 is an investigator-led, industry-funded, randomised, three-arm trial of platinum-sensitive HGSOC in earliest relapse at first rising serum CA125. Full accrual of 114 women was completed from 2019 to October 2022. SOLACE2 was designed to determine whether the PARP inhibitor (PARPi), olaparib, in combination with low dose cyclophosphamide, could prime the immune system, thereby increasing the proportion of responders to subsequent PARPi and immune checkpoint inhibitor therapy (ICI) (Durvalumab). Translational research was a priority, ensuring that tumour tissue was collected from diagnostic biopsy and/or initial surgery and for some cases, upon progression. Fortnightly blood samples were also collected throughout the priming period (12 weeks) and then monthly thereafter, with viable PBMCs stored for each sample.

We divided trial participants into three categories: best-responders, responders and poor-responders, using time from randomisation until progression (> 12 mo vs 6-12 mo vs >2 and <6 mo respectively). To better understand women’s treatment responses, we are comparing the immunological and genomic  (immuno-genomic) characteristics of the best-responders with the poor-responders (across all three treatment arms, until unblinding at the conclusion of the study). Analyses include Whole Exome Sequencing (WES) using FFPE tumour DNA and germline DNA; nanostring IO360 analysis of FFPE RNA; detailed multiplex IHC assessment of FFPE using OPALTM 7-colour multiplexed immunofluorescence images. By identifying the immuno-genomic features differing between best-responding and poor-responding cohorts, we will develop a better understanding of how responses to PARPi/ICI are generated and how to benefit more women with HGSOC. Preliminary data from a pilot study of a smaller cohort of these patients will be presented, enabling early insights and guidance of subsequent analyses of the full SOLACE2 cohort.