Veru Enrolls First Patient in International Phase 3 ARTEST Clinical Trial of Enobosarm in Metastatic Breast Cancer
-- Enobosarm is a novel targeted hormone drug to be evaluated in the 3(rd) line treatment of androgen receptor positive metastatic breast cancer --
-- A companion diagnostic test will be developed, validated, and used to select patients who are most likely to respond to enobosarm treatment --
-- The Phase 3 ARTEST study will be conducted in 49 clinical sites across the United States and Europe --
MIAMI, Oct. 13, 2021 (GLOBE NEWSWIRE) -- Veru Inc. (NASDAQ: VERU), an oncology biopharmaceutical company with a focus on developing novel medicines for the management of prostate and breast cancer, today announced that it has enrolled the first patient in its Phase 3 ARTEST registration trial of enobosarm, an oral selective androgen receptor (AR) targeting agonist, for patients with AR+ER+HER2- metastatic breast cancer who had tumor progression following treatment with estrogen blocking agents and CDK4/6 inhibitors.
"While endocrine therapies have been the mainstay of breast cancer treatment for decades, these therapies have all focused on the estrogen receptor. Targeting the AR, a demonstrated tumor suppressor, provides us with an opportunity to bring a truly novel hormone treatment approach to patients who have AR+ER+HER2- metastatic breast cancer," said Mitchell Steiner, M.D., Chairman, President and Chief Executive Officer of Veru Inc. "We already have substantial safety information about enobosarm therapy as it has been evaluated in 25 clinical trials comprising over 2,000 patients with approximately 350 patients dosed at 9mg or higher doses. Enobosarm is well tolerated and has also resulted in improvements in quality of life including reported better physical function, mobility, and pain in metastatic breast cancer patients. Furthermore, a recent Phase 2 study in heavily pretreated patients with metastatic breast cancer confirmed that enobosarm's efficacy was best in women that had 40% or greater expression of the androgen receptor in their breast cancer."
"Targeting patients expressing the androgen receptor allows us to focus a new endocrine approach on patients that have become resistant to existing therapies," said Adam Brufsky, M.D., Ph.D., Professor of Medicine, Associate Chief, Division of Hematology/Oncology and Co-Director, Comprehensive Breast Cancer Center at the University of Pittsburgh Medical Center. Dr. Brufsky is also the Principal Investigator of the ARTEST study. "I couldn't be more pleased that Veru is advancing enobosarm into a registration Phase 3 trial for the treatment of hormone receptor positive metastatic breast cancer in an effort to fill an unmet medical need benefitting these patients."
ARTEST Phase 3 Trial Design
The Phase 3 ARTEST (Androgen Receptor Targeting Agent, Enobosarm, for the Treatment of Metastatic ER+ Breast Cancer) clinical trial is an international, multicenter, open-label randomized, active control pivotal study evaluating the efficacy and safety of enobosarm 9mg oral daily dosing versus active control (exemestane +/- everolimus or SERM -- physician's choice) in the 3(rd) line metastatic treatment of approximately 210 metastatic AR+ ER+ HER2- advanced breast cancer patients who had tumor progression on a nonsteroidal aromatase inhibitor (anastrozole or letrozole), fulvestrant, and a CDK4/6 inhibitor. Enobosarm is being targeted to patients with positive androgen receptor staining using a threshold of >= 40% nuclei staining in tissue samples using a diagnostic test being developed and validated as a companion diagnostic test. The primary efficacy endpoint is median radiographic progression-free survival. Secondary endpoints include overall response rate (CR+PR), duration of response, overall survival, change in short physical performance battery (SPPB), and change in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ). The Phase 3 ARTEST study will be conducted in 49 clinical sites across the United States and Europe.
About the Enobosarm Phase 2 (G200802) Study
The Phase 2 clinical study was an open label, parallel design, randomized study to investigate the efficacy and safety of enobosarm 9mg and 18mg oral daily dosing in 136 heavily pretreated women with ER+ HER2- metastatic breast cancer who had breast cancer progression being treated with multiple lines of endocrine therapy and 90% also progressed on chemotherapy. Patients were randomized to receive enobosarm 9mg (n=72) or 18mg (n=64) oral daily dosing. The primary endpoint was clinical benefit rate at 6 months (defined as CR+PR+SD) by RECIST 1.1. Secondary endpoints included objective response rate, best overall response rate (complete responses + partial responses), radiographic progression-free survival (rPFS), and duration of clinical benefit. Median age was 60.8 years (35-83) for 9mg and 62.1 years (42-81) for the 18mg cohort. AR positivity (>10%) was centrally confirmed in 94.0% and 86.5% of the 9mg and 18mg cohorts, respectively.
The Phase 2 primary endpoint demonstrated clinically meaningful clinical benefit rate of 32% and 29% in the 9mg and 18mg daily enobosarm AR+ cohorts, respectively. At the time the study was terminated, the median duration of clinical benefit was not reached (NR) in the 9mg group (range 8.2 months to NR) and 14.1 months (range 11.0 to 16.5) in the 18mg group. A post-hoc AR expression subset analysis of these Phase 2 clinical data was conducted to evaluate the relationship of AR status with enobosarm antitumor efficacy. This subset analysis showed that the presence of the AR and the amount of AR expression in the breast cancer tissue predicted those women who were most likely to have an antitumor response to enobosarm. More specifically, the subset analysis combined randomized subjects from both the 9mg and 18mg cohorts who had known AR status determined by a central lab and who had measurable disease (n=84). The cutoff of 40% AR expression appeared to be the best level to enrich for subjects that were most likely to respond to enobosarm. The clinical benefit rate at 24 weeks was 52% at 40% AR staining versus 14% for 40% AR staining (p0.0004); best objective tumor response (PR + CR) was 34% at 40% AR staining versus 2.7% for 40% AR staining (p0.0003); and the median rPFS was 5.47 months at 40% AR staining versus 2.7 months for 40% AR staining (p0.001). Using this 40% cutoff, 57% of all women with AR+ER+HER2- metastatic breast cancer would qualify for treatment with enobosarm. Thus, the presence and degree of AR expression in breast cancer tissue was important for enobosarm's antitumor activity which is consistent with enobosarm being a targeted agent, or biomarker, that could select or enrich for subjects most likely to respond to enobosarm therapy.
Women being treated with 9mg or 18mg of enobosarm also reported significant improvements in quality-of-life measurements including mobility, anxiety/depression and pain discomfort. Overall, enobosarm was well tolerated with most of the observed adverse events being grade 1 and 2. Drug related severe adverse events (SAEs) (Grades 3-4) were observed in 6 patients (8.0%) at the 9mg and 10 patients (16.4%) at the 18mg dose. There were no reports of masculinizing side effects, increased hematocrit, and liver toxicity.
Enobosarm Clinical Development Program
Enobosarm is in clinical development for two indications: (i) a Phase 3 ARTEST clinical study evaluating enobosarm for the treatment of 3(rd) line metastatic AR+ER+HER2- breast cancer patients whose disease has progressed after treatment with a nonsteroidal aromatase inhibitor, fulvestrant, and a CDK4/6 inhibitor which is enrolling; and (ii) a Phase 3 ENABLAR-2 clinical study evaluating enobosarm + abemaciclib combination therapy as treatment of 2(nd) line metastatic AR+ER+HER2- breast cancer patients whose breast cancer has progressed after treatment with palbociclib and either a nonsteroidal aromatase inhibitor or fulvestrant combination. The Phase 3 ENABLAR-2 clinical trial is expected to begin enrollment in calendar Q4 2021. |
