Abstract 737P
Background
The Australian Ovarian Cancer Study identified 4 distinct molecular subtypes of high-grade serous ovarian cancer (HGSOC). C5 subtype is linked to poor prognosis and stemness behavior. We have previously described dependency of C5 HGSOC on genes related to microtubule dynamics. In vitro and vivo studies have shown sensitivity of C5 subtype HGSOC cell lines and patient-derived xenografts to tubulin-depolymerizing vinca alkaloids such as vinorelbine.
Methods
In this international, multi-center, single-arm phase II trial, patients with platinum-resistant HGSOC were consented for pre-screening using a 48-gene nanostring classifier on archival formalin fixed paraffin embedded tumor blocks to determine tumor molecular subtype. Patients with C5 subtype HGSOC on at least one tumor block were offered trial therapy where they were treated with vinorelbine until disease progression or intolerable toxicity. The primary end-point of this study is objective response rate (ORR) and is designed following a Simon’s Optimal two-stage design, with a null hypothesis of ORR 10% and an alternative hypothesis of ORR>30% following the treatment of C5 HGSOC patients with vinorelbine. A total of 10 patients are required for the first-stage of Simon’s two-stage design, with decision to proceed to the second-stage if 2 or more patients achieve an objective response.
Results
From 31/10/18 to 27/4/21, 144 patients were consented and 114 patients underwent pre-screening across 6 sites in Singapore and Australia. 8.8% (10/114) of pre-screened patients had C5 subtype HGSOC (Table). 5 patients have been enrolled and treated with vinorelbine monotherapy, of which 1/5 patients achieved a deep and durable response to vinorelbine. Table: 737P
Distribution of HGSOC molecular subtype amongst pre-screened patients
| HGSOC Subtype | Number of patients (%); N=114 |
| C1 | 48 (42.1) |
| C2 | 33 (28.9) |
| C4 | 4 (3.5) |
| C5 | 10 (8.8) |
| Mixed Subtype | 19 (16.7) |
Conclusions
C5 subtype HGSOC is unexpectedly rare in real-world practice. Encouraging response to vinorelbine monotherapy has been observed in C5 platinum-resistant ovarian cancer in this proof-of-concept trial.
Clinical trial identification
NCT03188159.
Editorial acknowledgement
Legal entity responsible for the study
Haematology-Oncology Research Group, National University Cancer Institute, Singapore.
Funding
National Medical Research Council, Singapore.
Disclosure
N.Y.L. Ngoi: Financial Interests, Personal, Invited Speaker: Thermofisher; Financial Interests, Personal, Invited Speaker: AstraZeneca. M. Friedlander: Financial Interests, Personal and Institutional, Other: AstraZeneca; Financial Interests, Personal and Institutional, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca; Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: GSK; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal and Institutional, Advisory Board: Novartis; Financial Interests, Personal and Institutional, Research Grant: Novartis; Financial Interests, Personal, Invited Speaker: Act Genomics; Financial Interests, Institutional, Funding: Beigene; Financial Interests, Institutional, Principal Investigator: Beigene; Non-Financial Interests, Personal, Advisory Role: Abbvie. D.S.P. Tan: Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: Bayer; Financial Interests, Personal, Other: Foundation Medicine; Financial Interests, Personal, Other: Janssen; Financial Interests, Personal, Other: Merck; Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Other: Tessa Therapeutics; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Bayer; Financial Interests, Personal, Research Grant: Karyopharm. All other authors have declared no conflicts of interest.