Context Therapeutics Doses First Patient in
Breast Cancer Trial

Coming off a $28.75 million initial public offering last week, Context Therapeutics dosed its first patient in a mid-stage breast cancer study assessing the combination of the progesterone receptor ONA-XR in combination with an estrogen receptor antagonist.

The Phase II SMILE study is evaluating Onapristone with Fulvestrant in patients diagnosed with ER-positive and HER2-negative metastatic breast cancer who have seen their illness progress despite treatment with endocrine therapy and CDK 4/6 inhibitors. The trial is being conducted by the Wisconsin Oncology Network. The primary outcome of the study is to determine the efficacy of the combination therapy in men and women with these forms of breast cancer.

Philadelphia-based Context, which is developing small molecule and immunotherapy treatments for breast and gynecological cancers, noted that both estrogen and progesterone are drivers in forms of breast cancer. Because of the broad use of antiestrogen drugs, overcoming resistance following endocrine therapies is a significant clinical challenge. Context hopes the study will demonstrate the combination treatment’s efficacy in addressing this resistance and improving patient outcomes.

The primary endpoint of the study will be the overall response rate, which is the proportion of patients with complete or partial tumor response. Secondary endpoints include duration of tumor response, progression-free survival, disease control rate, time to response, and incidence of adverse events.

Martin Lehr, chief executive officer of Context Therapeutics, said he hopes the Phase II study will offer a clear picture of how ONA-XR, an extended-release orally-administered full antagonist of progesterone, works in advanced ER+, PR+, HER2- breast cancer. The outcome of this study will determine the course of a potential Phase III trial, Lehr noted.

In addition to these forms of breast cancer, ONA-XR is also being assessed in multiple Phase II studies in ovarian and endometrial cancers.

The SMILE study will include up to 39 patients with ER+, PR+, HER2- metastatic breast cancer who have progressed on aromatase inhibitor and CDK4/6 inhibitor combination therapy. The study will take place across 19 sites operated by the Wisconsin Oncology Network (WON).

In May of this year, Context dosed its first patient with ONA-XR in the Phase II ONWARD 221 trial in patients with metastatic endometrial cancer. That study, which is a collaboration between Context and Jefferson Health’s Sidney Kimmel Cancer Center, is evaluating the addition of a progesterone receptor antagonist to the antiestrogen, anastrozole in patient with this indication who have failed prior therapy.

The Phase II study is expected to include up to 25 patients who are ER+ and/or PR+ and who have received prior chemotherapy treatment. The primary endpoint of this Phase II study is ORR, overall response rate. Secondary endpoints include duration of response, clinical benefit rate and progression-free survival. Additionally, the trial will evaluate the safety and pharmacological profile, as well as biomarker analyses to explore predictive factors of response to complete hormone blockade to inform additional ongoing Phase II studies and a planned Phase III trial.

Currently, there are no approved therapies that selectively target PR+ cancers. For Context, the collaboration with WON comes less than a week after the company closed its IPO. The company, which is listed on the Nasdaq exchange under the ticker symbol “CNTX,” raised $28.75 million in its debut. The company sold 5,750,000 shares at $5 per share for its IPO.