E-Poster Presentation 33rd Lorne Cancer Conference 2021

Comparing the immuno-genomic landscape of high grade serous ovarian carcinoma patients in the SOLACE2 clinical trial (#155)

Nirashaa Bound 1 , Cassandra Vandenberg 1 2 , Kristy Shield-Artin 1 , Gayanie Ratnayake 3 , Matthew Wakefield 1 , Tony Papenfuss 1 , Michael Friedlander 4 , Chee Lee 5 6 , Magdalena Plebanski 7 , Clare L Scott 1 8 9
  1. The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
  2. Melbourne University , Parkville, VIC, Australia
  3. Royal women's hospital, Parkville, VIC , Australia
  4. Sydney and Prince of Wales Clinical School, University of New South Wales, Prince of Wales Hospital, Sydney, NSW, Australia
  5. St George Hospital, Sydney, NSW, Australia
  6. National Health and Medical Research Council (NHMRC) Clinical Trials Centre, Sydney, NSW, Australia
  7. Cancer Ageing and Vaccines (CAVA), Translational Immunology and Nanotechnology Program, RMIT university, Melbourne, VIC, Australia
  8. Peter MacCallum Cancer center, Melbourne, VIC, Australia
  9. The Royal Melbourne Hospital, Melboune, VIC, Australia

Current first-line treatments for high grade serous ovarian carcinoma (HGSOC) combine cytoreductive surgery with platinum-taxane-based chemotherapy, to which 85% of patients show an initial response. However, only 30% of women will remain in remission, with the remainder relapsing within 4-16 months with progressively more chemo-resistant disease, underlying the need for more curative therapeutic regimens.

 

SOLACE2 is an investigator-led, industry-funded, randomised, three-arm trial in platinum-sensitive HGSOC at earliest relapse with rising serum CA125. It commenced accrual in 2019, addressing whether the PARP inhibitor, Olaparib, in combination with low dose cyclophosphamide (LDCy), can prime the immune response, increasing the proportion of responders to subsequent PARPi and checkpoint inhibitor therapy with Durvalumab (IO).

 

SOLACE2 was designed to maximise translational investigation and enable a better understanding of PARPi response, mechanisms of drug resistance, and to develop rational approaches to achieving long-term tumour remission in OC. By identifying the mechanism by which PARPi/IO therapy impacts prolonged remission or even cure, we aim to study how to deploy this mechanism for the benefit of more women with HGSOC. For initial translational analyses, patients will be allocated to one of three categories: best responders (predicted to include super-responders), responders and poor-responders based on their time on study. By functionally characterizing the immunological and genomic (immuno-genomic) features from best-responding patients, we will develop an understanding of how to generate responses more broadly. Over the next four years, we aim to perform novel immunological and genomic analysis of 114 SOLACE2 patient samples, consisting of archival tissue, fresh tumour samples and fortnightly (x6), then monthly, blood samples. Analysis will include Whole Exome Sequencing (WES) of tumour and germline, Flow sorting and cytometric analysis of PBMCs, nanostring analysis of the tumour microenvironment (IO360) and detailed multiplex IHC assessment using OPAL. An initial pilot study on a smaller cohort will be conducted as proof of concept and to guide subsequent analyses. Preliminary data and design of this pilot study will be presented.