747P - SOLACE2: A phase II randomized trial of olaparib (O) and durvalumab (D) with or without low dose cyclophosphamide (LDCy) in platinum-sensitive recurrent ovarian cancer (PSROC)

Background

Preclinical data shows that T-cell priming by LDCy leads to greater responses in PSROC treated with LDCy and O compared with O alone. We hypothesized that priming with LDCy would also enhance the treatment effect of D with O.

Methods

In this non-comparative phase 2 trial, women naïve of D and O with first recurrence PSROC and asymptomatic CA125 progression were randomly assigned in 1:1:1 ratio to receive: (A) 12 weeks induction with O followed by maintenance O-D, (B) 12 weeks LDCy-O followed by maintenance O-D, and (C) O continuous therapy. The primary endpoint was progression-free survival (PFS) rate at 36 weeks (PFS36). Response according to RECIST and CA125, safety, and a novel immune signature based on tumor microenvironment were also assessed.

Results

A total of 114 patients underwent randomization. Median follow-up was 36.1 months with 89.5% progression events. PFS36 rates were 47.4% (95% CI 31.0-62.1), 48.7% (95% CI 32.5-63.2) and 35.1% (20.4-50.2) for arms (A), (B) and (C) respectively. The median PFS was 8.2, 8.3 and 5.7 months respectively. Objective responses were observed in 42.1%, 53.8% and 35.1% respectively. Table summarizes outcomes according to homologous recombinant deficiency (HRD) status. Immune signature expression was associated with longer PFS regardless of treatment arms (N=98; HR 0.31, 95% CI 0.19-0.48), including BRCA wild-type HRD ovarian cancer (N=56; HR 0.39, 95% CI 0.20-0.75). The safety profile of LDCy, O and D was consistent with previous reports, but higher rates of treatment-related adverse events occurred in arm (B) as compared with arms (A) and (C). Table: 747P

Conclusions

LDCy-O, or O alone, followed by maintenance O-D did not significantly improve PFS as compared with O continuous therapy. A previously unreported immune signature is prognostic for greater PFS with olaparib-based treatment, including within BRCA wild-type HRD ovarian cancer.

Clinical trial identification

ANZCTR: ACTRN12618000686202.

Editorial acknowledgement

Legal entity responsible for the study

The University of Sydney.

Funding

This research was conducted with support from AstraZeneca and its Group of Companies.

Disclosure

C.L. Scott: Financial Interests, Personal, Advisory Board, Scientific Advisory Board, member, Sept 2021 - current: OncologyOne; Financial Interests, Institutional, Full or part-time Employment, Laboratory Head and Head Clinical Discovery Translation, WEHI: Walter and Eliza Hall Institute of Medical Research; Financial Interests, Institutional, Full or part-time Employment, Chair, Gynaecological Cancer: University of Melbourne; Financial Interests, Institutional, Full or part-time Employment, Specialist Medical Oncologist: Peter MacCallum Cancer Centre, Melbourne Health; Financial Interests, Institutional, Royalties, Royalties via my institution Walter and Eliza Hall Institution of Medical Research: Venetoclax; Financial Interests, Institutional, Research Grant, Research grant, PI, To my laboratory, including provision of drugs for research: AstraZeneca; Financial Interests, Institutional, Funding, Research grant, PI, To my laboratory, including provision of drug: Eisai, Sierra Oncology; Financial Interests, Institutional, Other, In kind research support including provision of drug, to my laboratory: Clovis Oncology; Financial Interests, Institutional, Other, In kind research support, provision of drug, to my laboratory: Beigene; Financial Interests, Institutional, Coordinating PI, Funding of the SOLACE2 trial, Study Chair and PI, Steering committee, Chair: AstraZeneca; Financial Interests, Institutional, Coordinating PI, Provision of study drug, Eribulin, for the EPOCH trial, Study Chair: Eisai; Financial Interests, Institutional, Coordinating PI, Provision of study drug, Pembrolizumab, for the EPOCH trial, Study Chair: MSD; Financial Interests, Institutional, Steering Committee Member, EMBRACE clinical trial, AZ supplied olaparib, My role, member of the steering committee; performing translation (funds from govt grant): AstraZeneca; Financial Interests, Institutional, Funding, Research grant, To my laboratory, including provision of drug for research: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant, Research grant, PI, to my laboratory, including provision of drug: Ideaya Biosciences; Non-Financial Interests, Advisory Role, Advisory Boards, member: AstraZeneca; Non-Financial Interests, Advisory Role, Advisory Board, Member: Eisai; Non-Financial Interests, Advisory Role, Advisory Board, member: Sierra Oncology, Roche, Takeda, MSD, GSK; Non-Financial Interests, Advisory Role, Advisory Board, Chair: EpsilaBio; Non-Financial Interests, Institutional, Proprietary Information, Research collaboration, provision of drugs and discussion of commercial in confidence information: AstraZeneca, Eisai; Non-Financial Interests, Institutional, Product Samples, Research collaboration, provision of drugs: AstraZeneca, Eisai; Non-Financial Interests, Institutional, Proprietary Information, Research collaboration, provision of drugs: Boerhinger Ingelheim, Ideaya Biosciences; Non-Financial Interests, Other, Board, Chair: International Rare Cancer Initiative; Non-Financial Interests, Leadership Role, GCIG Executive Board of Directors, Member: Gynaecological Cancer InterGroup (GCIG), Director; Other, PI, funded by theAustralian Government as part of the Australian Genomic Cancer Medicine Centre (AGCMC) (OMICO).: Australian Rare Cancer Portal. M.L. Friedlander: Financial Interests, Personal, Advisory Board, /Speaker: AstraZeneca, GSK, MSD; Financial Interests, Personal, Speaker, Consultant, Advisor: Limbic; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Institutional, Research Funding: AstraZeneca, Novartis, Beigene; Non-Financial Interests, Institutional, Principal Investigator: AstraZeneca, Beigene. K. Francis: Financial Interests, Personal, Invited Speaker, Castrate sensitive metastatic prostate cancer meeting: Janssen; Financial Interests, Personal, Invited Speaker, Breast cancer meeting on management of advanced breast cancer: Gilead. N. Bound: Financial Interests, Institutional, Research Grant: AstraZeneca, Boehringer Ingelheim, IDEAYA biosciences, Eisai Inc.. Y.C. Lee: Financial Interests, Institutional, Invited Speaker, Educational events: AstraZeneca; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Institutional, Research Grant: BeiGene. J. Lombard: Financial Interests, Personal, Advisory Board, Ad Board for durvalumab + olaparib in uterine cancer: AstraZeneca; Financial Interests, Personal, Invited Speaker, educational dinner talk June 2023: Novartis; Financial Interests, Personal, Other, registration for virtual ESMO attendance October 2023: Novartis; Financial Interests, Personal, Invited Speaker, Speaker educational dinner March 2023: Eisai; Financial Interests, Personal, Invited Speaker, educational dinner speaker: Gilead; Financial Interests, Personal, Other, payment for registartion for international virtual meeting (ASCO) June 2022: GSK. S.E. Baron-Hay: Financial Interests, Personal, Advisory Board, Participation in an advisory board: Pfizer, Eisai, Novartis, GSK; Financial Interests, Personal, Advisory Board, Participation in an advisory board Invited speaker at education meeting: AstraZeneca; Financial Interests, Personal, Invited Speaker, Talks at Gilead education meeting Development of education slide deck: Gilead. Y. Antill: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo; Financial Interests, Institutional, Research Funding: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca. C. Shannon: Financial Interests, Personal, Advisory Board: AstraZeneca, Gilead, GSK, MSD. P.J. Beale: Financial Interests, Personal, Advisory Board: GSK. K. Shield-Artin, M. Wakefield, C. Vandenberg: Financial Interests, Institutional, Research Funding: AstraZeneca, Boehringer Ingelheim, Ideaya Biosciences, Eisai Inc. M. Plebanski: Financial Interests, Institutional, Research Funding: AstraZeneca; Non-Financial Interests, Personal, Advisory Board: Ovarian Cancer Research Foundation ; Financial Interests, Institutional, Other: Smartinject. C.K. Lee: Financial Interests, Personal, Advisory Board: AstraZeneca, Amgen, Roche, Janssen, Gilead, MSD, GSK, Novartis, Merck kGA; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Amgen, Merck kGA, Novartis, Roche. All other authors have declared no conflicts of interest.