The EMBRACE trial and AUTO-CHECK study were developed and submitted with support from GCCTI.
EMBRACE is a phase 2 clinical trial of the poly adenosine diphosphate-ribose polymerase (PARP) inhibitor, olaparib, in homologous recombinant- (HR-) deficient metastatic breast and relapsed ovarian cancer in patients without germline mutations in BRCA1 and BRCA2.
The aim of this trial is to determine if tumours with somatic inactivating mutations of BRCA1 or BRCA2, germline or somatic inactivating mutations in other genes involved in repairing HR defects (e.g. PALB2, CHEK2, ATM, RAD51), or somatic BRCA1 gene silencing by promoter methylation are similarly susceptible to PARP inhibition as tumours with germline inactivating mutations of BRCA1 or BRCA2.
This trial was funded in December 2016 by Cancer Australia and is led by Dr Katrin Sjoquist with support from ANZGOG and BCT.
The study is an open-label, single-arm, signal-seeking, multi-centre phase 2 clinical trial of two molecularly enriched cohorts:
- Relapsed platinum-sensitive high-grade serous ovarian cancer not yet treated for relapsed disease;
- Triple negative breast cancer.
Both cohorts are treated with olaparib 300 mg twice-daily until disease progression or unacceptable toxicity. The primary aim is to evaluate the activity of olaparib in each molecularly-enriched cohort.
Recruitment to the EMBRACE trial finished on 31 March 2022. A total of 22/60 participants were enrolled from 12 sites across Australia. More than 200 patients were screened during the recruitment period. Preparation for publication of the trial results is underway.
AUTO-CHECK is a translational research study. It looks at the molecular determinants of autoimmunity and immune adverse events in advanced cancer patients who have been treated with immune checkpoint inhibitors (ICIs).
The hypothesis of this study is that a group of patients with a genetic susceptibility to autoimmunity are more likely to develop an immune-related adverse event (IRAE) after treatment with ICIs.
This study was funded in January 2017 by Cancer Australia and is led by Prof Matthew Cook (CIA) and Dr Sonia Yip.
AUTO-CHECK collected biospecimens from six multi-site investigator-initiated trials across four CTGs (ALTG (now known as TOGA), ANZGOG, ANZUP, and COGNO). These trials span five tumour types: mesothelioma (DREAM); non-small cell lung cancer (NIVORAD, ILLUMINATE), endometrial (PHAEDRA), renal cell (KEYPAD), and glioblastoma (NUTMEG) – each trial using ICIs.
The study aims include to:
- Investigate baseline characteristics of peripheral blood mononuclear cells (PBMCs; enumeration and molecular) that are predictive of IRAEs
- Characterise changes in PBMCs after treatment with ICI and also after an IRAE
- Identify common and rare genetic variants that segregate with IRAEs
- Investigate associations between IRAEs and tumour response
AUTO-CHECK includes 257 participants with over 450 real-time blood shipments from 48 sites to the central lab situated in the Australian National University. Approximately 50 participants had blood samples following an IRAE. As at Q3 2022, serological profiling is complete. Whole genome sequencing has been completed. Immune profiling of PBMCs is ongoing.