On October 11, 2018 Context Therapeutics reported Phase 1 data for its investigational new drug, Apristor (Onapristone extended release), an oral progesterone receptor antagonist that is being developed for progesterone receptor-positive (PR+) cancers (Press release, Context Therapeutics, OCT 11, 2018, View Source [SID1234529858]). Data from the study showed that Apristor, a novel extended release formulation of onapristone, was well tolerated and provided a clinical benefit in patients with previously treated recurrent or metastatic progesterone receptor-driven breast, ovarian and endometrial cancers. These findings were published in the medical journal PLOS One and can be accessed here.

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"I’m encouraged by the early data seen in this Phase 1 study of Apristor. Apristor appears to be well tolerated, with responses seen across a broad range of PR+ cancers," commented Paul Cottu, M.D., Ph.D., Deputy Head, Department of Oncology, Institute Curie, and lead investigator for the trial. "Many hormonally-driven malignancies are difficult to treat, and new agents are clearly needed. Targeted therapies, including Apristor, have the potential not only to add therapeutic options for our patients but also to reduce or delay the need for chemotherapy, possibly changing the way many of these malignancies are treated."

"Context is pleased with the Phase 1 Apristor study results demonstrating clinical efficacy across PR+ cancers in heavily pretreated patients who are typically unresponsive to currently approved hormonal treatments," stated Martin Lehr, CEO of Context Therapeutics. "We believe Apristor has the potential to be the first anti-progestin approved to treat cancer and we are rapidly advancing Apristor into multiple Phase 2 trials with a goal of addressing significant medical needs."

Apristor Phase 1 Data in Patients with PR+ Breast, Ovarian, or Endometrial Cancer

Design

52 patients were randomized to five cohorts of Apristor (onapristone extended release tablets 10, 20, 30, 40 or 50 mg BID; n=46), or immediate release onapristone 100 mg QD (n=6) until progressive disease or intolerability. Primary endpoint was to identify the recommended phase 2 dose. Secondary endpoints included safety, clinical benefit and pharmacokinetics.

Results

Tumor diagnosis includes: endometrial carcinoma 12; breast cancer 20; ovarian cancer 13; and other 7. Median age was 64 (36-84). No dose limiting toxicity was observed with reported liver function test elevation related only to liver metastases. The recommended Phase 2 dose (RP2D) was 50mg BID. For patients on Apristor (n=46), dose responsive activity was noted, and 20% (9 of 46) patients had clinical benefit ≥24 weeks. The most common side effects were asthenia and low-grade, transient gamma-glutamyl transferase elevations.

Clinical Activity

Tumor assessments strongly suggested anti-cancer efficacy, even in heavily pretreated patients. In Apristor treated patients, 20 of 46 patients experienced stable disease as best response and 9 of 46 patients had durable disease stabilization.

Conclusions

The new extended release formulation of Onapristone (Apristor) was well tolerated and resulted in clinical benefit in heavily pretreated patients with ovarian, breast and uterine endometrial cancers. The recommended Phase 2 dose for Apristor is 50mg BID. There were no grade 3-4 LFT elevations in the absence of progressive liver metastases, no new safety signals were observed, and dose limiting toxicity was not observed. The data support the development of Apristor in PR+ cancers.

About Apristor

Apristor, an investigational new drug, is an oral progesterone receptor (PR) antagonist. PR is an oncogene that is enriched in up to 70% of all breast, ovarian, and endometrial cancers. Apristor is being developed to treat metastatic breast, ovarian and endometrial cancers.