Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2019

SOLACE2: A phase II randomised trial of immune priming by olaparib-cyclophosphamide prior to olaparib-durvalumab in asymptomatic, platinum-sensitive recurrent ovarian cancer (#288)

Clare Scott 1 2 3 4 , Chee Khoon Lee 4 5 6 , Yeh Chen Lee 4 5 7 8 , Michael Friedlander 4 7 8 , Stephanie Hollis 5 , Katrina Diamante 5 , Claire Davies 4 , Martin Stockler 5 , Magdalena Plebanski 9
  1. The Royal Melbourne Hospital, Melbourne, VIC, Australia
  2. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  3. Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia
  4. Australia New Zealand Gynaecological Oncology Group (ANZGOG), Sydney, NSW, Australia
  5. National Health and Medical Research Council Clinical Trials Centre (NHMRC CTC), Camperdown, NEW SOUTH WALES, Australia
  6. Department of Medical Oncology, St George Hospital, Sydney, NSW, Australia
  7. Prince of Wales Hospital, Randwick, NSW, Australia
  8. Royal Hospital for Women, Randwick, NSW, Australia
  9. School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia

Background

Up to 50% of high grade serous ovarian cancer (HGSOC) may have impaired DNA repair by homologous recombination. PARP inhibitor (PARPi) therapy may be complementary to immune checkpoint inhibitor therapy, potentially causing greater mutational burden and subsequently better immune recognition of the tumour. Conversely, low dose cyclophosphamide (LDCy) supports anti-tumour immunity, primarily by depleting the T-regulatory cells and causing downstream boosts to T-cell response to cancer. The Phase 1 SOLACE study showed that the combination of olaparib and LDCy is well-tolerated and active in HGSOC. We posit that immunological priming with LDCy and olaparib could improve the subsequent response to PARPi/checkpoint inhibitor dual therapy in women with HGSOC at first relapse.

Methods

SOLACE2 is an open-label, 3-arm, multicentre, phase II randomised trial. A total of 114 patients will be randomised in 1:1:1 ratio to (Treatment A) 3 months of olaparib monotherapy followed by olaparib and durvalumab; versus (Treatment B) 3 months of olaparib and LDCy followed by olaparib and durvalumab; versus (Treatment C) olaparib monotherapy. Key inclusion criteria is women with platinum sensitive ovarian, fallopian tube or primary peritoneal cancer, at first asymptomatic GCIG CA125 progression following primary treatment. Patients with RECIST non-measurable disease or no disease are eligible. Primary outcome measure is progression-free survival rate (PFS) at 36 weeks. Secondary endpoints include objective response rate and PFS by RECIST 1.1 or GCIG CA125 criteria; adverse events profile; health-related quality of life; and time to first subsequent treatment. The study includes mandatory archival tumour tissue availability for genomic profiling and ctDNA collection at defined time points. Correlative studies include longitudinal analyses of immune signatures over the three month priming period. SOLACE2 is open for accrual at 15 hospital sites across Australia.