K. Amillano (Reus, Spain)

Hospital Universitari Sant Joan de Reus, Reus, Spain

Author Of 1 Presentation

 On-Demand ePoster Display

40TiP - SOLTI-1802 ONAWA Trial: A Window of Opportunity Trial of Onapristone (ONA) in Postmenopausal Women with Estrogen and Progesterone Receptor-Positive/HER2-negative (ER+/PgR+/HER2-) Early Breast Cancer (EBC)

Abstract

Background

PgR expression is a biomarker of ER functionality, cellular progression to malignancy, and response to endocrine therapy (ET) in HR+ BC. ONA, a type I antiprogestin showed activity in patients with metastatic BC, but early trials with its immediate release formulation showed liver toxicity and further studies were halted. The development of a new extended-release formulation (Context Therapeutics, PA, USA), which is associated with a lower liver toxicity (Cottu PH, PLOS ONE, 2018) has strongly supported the relaunching of ONA clinical development. ONA blocks Ser294 phosphorylation of PgR, a posttranslational event associated with elevated PgR transcriptional activity coupled to rapid PgR turnover and also, downregulates PgR gene targets both in tumor cells expressing a sumo-deficient/phospho-mimic activated (KR) and non-activated (WT) PgR phenotype, independent to the presence of progesterone. Considering BC heterogeneity and that PgR analysis by standard immunohistochemistry (IHC) does not perfectly correlate with PgR target gene expression, the identification of biomarkers allowing the selection of patients with PgR-driven tumors that may benefit from antiprogestins treatment is currently an unmet need.

Trial design

ONAWA is an open-label, single arm, multicenter window of opportunity clinical trial of ONA (50 mg extended-release tablets BID for 21 days) for postmenopausal women with EBC amenable to receive a short course of ET before surgery. Ten patients with ER+/PgR+/HER2- and ki67 ≥ 15% BC will be enrolled at 4 sites of the SOLTI network. The primary objective is to evaluate the biological activity of ONA by the rate of Complete Cell Cycle Arrest determined by Ki67 (≤2.7%). Secondary endpoints include safety and correlating biological activity with IHC of tumor expression (ER, PgR, Ser294-PgR, CD24, CD44, ALDH1, Ki67), estradiol, and progesterone blood levels, and gene expression profile (NanoString nCounter® Breast 360TM panel). The study was approved in July 2020 and recruitment started in November 2020. Seven patients have been enrolled at the time of this submission.

Clinical trial identification

NCT04142892; EudraCT Number: 2019-001433-13.

Legal entity responsible for the study

SOLTI Breast Cancer Research Group.

Funding

Context Therapeutics.

Disclosure

X. González-Farré: Honoraria (self), Non-remunerated activity/ies: Roche; Honoraria (self): Eisai; Honoraria (self): SOLTI. P. Villagrasa: Speaker Bureau/Expert testimony: NanoString. A. Prat: Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Roche; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Advisory/Consultancy, Research grant/Funding (self): NanoString; Advisory/Consultancy: Oncolytics Biotech; Advisory/Consultancy: Amgen; Advisory/Consultancy: Puma. C. Saura Manich: Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Celgene; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Daiichi Sankyo; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Eisai; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Hoffman-La Roche; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Genomic Health; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Sharp and Dhome España SA; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Philips Healthwork; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Pierre Fabre; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: prIME Oncology; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Puma; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Synthon; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Sanofi Aventis. All other authors have declared no conflicts of interest.

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