Primary Results of Onawa (Solti-1802) Trial: A Window Of Opportunity Trial Of Onapristone In Postmenopausal Women With Progesterone Receptor-Positive/Her2-Negative Early Breast Cancer

PGR is an estrogen-responsive gene and progesterone receptor (PR) expression, evaluated by immunohistochemistry (IHC), is used as a clinical biomarker of estrogen signaling and estrogen receptor (ER) functionality.1

Despite the well-studied role of PGR as mitogen and independent ER activator, anti-progestins for the treatment of BC have been poorly tested. While limited success for anti-progestins has been reported in metastatic setting2-3-4, two more recent window of opportunity (WOO) trials have shown an anti-proliferative effect in treatment-naive patients diagnosed with early BC.5-6

Onapristone (ONA), a type 1 anti-progestin, was shown to have anti-tumor activity as a single agent in patients with metastatic BC.2 However, its clinical development was halted in 1995 following the occurrence of liver function test abnormalities. More recently, a highly-purified, extended-release formulation of onapristone (ONA XR) has been developed and findings from phase l-ll studies have shown clinical benefit and good tolerance in heavily pre-treated patients.7

ONAWA (NCT04142892) is the first WOO study to assess whether ONA XR may inhibit tumor proliferation during the short-term preoperative treatment of women diagnosed with operable BC. Here, we report the results of the primary efficacy and safety analysis, along with correlative translational analyses.