On September 29, 2015 GTx, Inc. (Nasdaq: GTXI) reported the enrollment of the first patient into its Phase 2 clinical trial of enobosarm (GTx-024) to treat women with advanced, estrogen receptor positive (ER+), androgen receptor positive (AR+) breast cancer (Press release, GTx, SEP 29, 2015, View Source [SID:1234507609]). Enobosarm, a selective androgen receptor modulator (SARM), is the Company’s lead product candidate. Schedule your 30 min Free 1stOncology Demo! "Additional endocrine directed therapies are needed for the treatment of estrogen receptor positive breast cancer as many women who respond to hormonally directed therapy will continue to demonstrate response with subsequent hormonal manipulation," said Robert J. Wills, Ph.D., Executive Chairman of GTx. "We believe that enobosarm may provide a new hormonal approach for the treatment of estrogen receptor positive breast cancer and may delay the need for chemotherapy in these women."
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The open-label, multi-center, multinational Phase 2 clinical trial (NCT02463032) will assess the efficacy and safety of orally administered enobosarm in up to 88 evaluable patients with metastatic or locally advanced, ER+/AR+ breast cancer. Patients will receive either enobosarm 9 mg or 18 mg given daily for up to 24 months. The initial stage of evaluation will be assessed among the first 18 evaluable patients for each dosing arm. If at least 3 of 18 patients achieve clinical benefit at week 24, then the trial will proceed to the second stage of enrollment for that dosing arm to assess clinical benefit in a total of 44 evaluable patients per arm. Clinical benefit is defined as a complete response, partial response, or stable disease, as measured by Response Evaluation Criteria in Solid Tumors (RECIST) at 24 weeks. The lead investigator for the trial is Dr. Beth Overmoyer from the Dana Farber Cancer Institute and the Harvard Medical School.
About enobosarm
Enobosarm, a selective androgen receptor modulator (SARM), has been evaluated in 23 completed or ongoing clinical trials enrolling over 1,500 subjects at doses ranging from 0.1 mg to 100 mg. At all evaluated dose levels, enobosarm was observed to be generally safe and well tolerated.
Most recently, enobosarm 9 mg has been tested in a Phase 2, proof of concept clinical trial of 22 postmenopausal women with ER+ metastatic breast cancer who have previously responded to endocrine therapy. Seventeen of the 22 patients were confirmed to be AR+. Six of these 17 patients demonstrated clinical benefit at six months. Seven patients in total (one patient with indeterminate AR status) achieved clinical benefit at six months. The results also demonstrated that, after a median duration on study of 81 days, 41 percent of all patients (9/22) achieved clinical benefit as best response and also had increased PSA which appears to be an indicator of AR activity. Enobosarm was well tolerated. The most common adverse events reported were pain, fatigue, nausea, hot flash/night sweats, and arthralgia.
About ER+/AR+ Breast Cancer
Breast cancer is the most commonly diagnosed cancer in women, and one in eight women will develop invasive breast cancer in their lifetime. In 2012, 1.7 million women were diagnosed with breast cancer, and there were 6.3 million women alive who had been diagnosed with breast cancer in the previous five years. Clinical assessment of breast cancer provides for routine characterization of receptor status including the presence or absence of estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2 (HER2) in the tumor tissue. Receptor status is used to assess metastatic potential as well as to guide treatment decisions. The majority of breast cancers are considered hormone receptor positive (expressing ER or progesterone receptor). Approximately 70 percent of women in the U.S. with breast cancer have ER+ tumors, and 75 to 90 percent of these cancers are also AR+.
Estrogen promotes the growth of breast cancers that are hormone receptor positive. Therefore, treatment is directed at blocking the effects of estrogen on the breast cancer either through blocking the estrogen receptor or minimizing the production of estrogen. This endocrine therapy is the cornerstone of treatment for the majority of women with hormone receptor positive advanced breast cancer and is the preferred initial treatment over alternative approaches such as chemotherapy, due to its efficacy and favorable safety profile. Patients who respond to one endocrine therapy are likely to respond to subsequent hormonal therapies. Therefore, the standard of care for women with hormone receptor positive breast cancer typically involves the sequencing of endocrine agents until intolerance or development of resistance occurs, or metastatic progression necessitates a transition to chemotherapy.
Enobosarm may offer an alternate hormonal approach for the treatment of endocrine sensitive advanced breast cancer prior to the introduction of chemotherapy.