On November 28, 2016 GTx, Inc. (Nasdaq: GTXI) reported that enobosarm achieved the pre-specified primary efficacy endpoint in the 9 mg dose cohort from patients in both stage 1 and the ongoing stage 2 of its Phase 2 clinical trial in women with advanced, estrogen receptor positive (ER+), androgen receptor positive (AR+) breast cancer (Press release, GTx, NOV 28, 2016, View Source [SID1234516811]). The primary efficacy endpoint requires at least nine patients (out of a total of 44 evaluable patients) to achieve clinical benefit, defined as either a complete response, partial response or stable disease, as measured by Response Evaluation Criteria in Solid Tumors (RECIST) at 24 weeks of treatment. In this ongoing trial, the efficacy endpoint was achieved in the first 22 confirmed evaluable patients, and the trial will continue enrolling and treating eligible patients with enobosarm until 44 evaluable patients have completed the trial. Enobosarm has been well tolerated among patients treated to date in the 9 mg dose cohort with the majority of adverse events being either grade 1 or 2.

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The Company plans to report top-line clinical results from these 22 evaluable patients from the 9 mg dose cohort in December 2016, and expects to report top-line clinical results from the full study by the middle of 2017, following completion of the clinical trial.

"Demonstrating success with the 9 mg dose cohort sooner than expected in 22 patients is a significant milestone for the enobosarm program and GTx, and we look forward to seeing top-line response data in all 44 evaluable patients," said Robert J. Wills, Ph.D., Executive Chairman of GTx. "In addition, with these results in hand, we will be discussing how best to advance the development of enobosarm with potential partners."

About the Phase 2 Clinical Trial in ER+/AR+ Breast Cancer

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 orally-administered enobosarm (9 mg or 18 mg) daily for up to 24 months. The two dose cohorts in the trial will be treated independently for the purpose of assessing efficacy. The first stage of evaluation will be assessed among the first 18 evaluable patients for each cohort. 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 cohort to assess clinical benefit in a total of 44 evaluable patients per arm. As reported in September and November, 2016, respectively, patients in both the 9 mg and 18 mg cohorts demonstrated sufficient clinical benefit among the first 18 evaluable patients in each such cohort to advance to the second and final stage of the clinical trial. 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 24 completed or ongoing clinical trials enrolling over 1,500 subjects, of which approximately 1,000 subjects were treated with enobosarm 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. Previously, 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+, and 6 of those 17 patients demonstrated clinical benefit at six months. In total, 7 patients (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 world-wide 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.

On November 28, 2016 Epizyme, Inc. (NASDAQ:EPZM), a clinical-stage biopharmaceutical company creating novel epigenetic therapies, reported advancements in the Company’s clinical programs evaluating tazemetostat, its first-in-class EZH2 inhibitor (Press release, Epizyme, NOV 28, 2016, View Source [SID1234516810]). The U.S. Food and Drug Administration (FDA) has granted tazemetostat Fast Track designation in patients with diffuse large B-cell lymphoma (DLBCL) with EZH2 activating mutations. Additionally, Epizyme is focusing its Phase 2 registration-enabling study in adult patients with genetically-defined solid tumors on those cancers marked by loss of INI1, and has expanded enrollment in the epithelioid sarcoma cohort of the study based on encouraging early activity in this patient population.

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"We are very proud of the continued advancement of our tazemetostat clinical program in both non-Hodgkin lymphoma and genetically-defined solid tumors, important areas of unmet medical need for patients with cancer," said Robert Bazemore, president and chief executive officer, Epizyme. "These developments reflect the execution of our strategy to identify the patient groups who may benefit most from tazemetostat, and our efforts to bring this investigational medicine to patients as quickly as possible."

NHL Program Update: Fast Track Designation for DLBCL Subtype
The FDA has granted Fast Track designation for the investigation of tazemetostat for the treatment of patients with relapsed or refractory DLBCL whose tumors carry an EZH2 activating mutation. Tazemetostat inhibits EZH2, a histone methyltransferase that is increasingly understood to play a role in the growth and proliferation of a number of cancers, including DLBCL, the most commonly diagnosed form of NHL.

The FDA Fast Track program is designed to facilitate the development of important new drugs and to provide patients access to those drugs more quickly. The designation enables early and frequent communication between FDA and a product sponsor throughout the drug development and review process. Through the Fast Track program, a product may be eligible for priority review at the time of a new drug application (NDA) filing and may also be eligible to submit completed sections of the NDA on a rolling basis before the complete application is submitted. These expedited processes can potentially reduce development time and cost associated with bringing a drug to market.

Genetically Defined Solid Tumor Program Update: Focus on INI1-Negative Tumors
Following review by the Independent Data Monitoring Committee, Epizyme has expanded the epithelioid sarcoma cohort of its ongoing Phase 2 trial in adult patients with INI1-negative solid tumors. This expansion is based on encouraging early activity seen, including confirmed objective responses, in the cohort. The company plans to enroll an additional 30 patients with epithelioid sarcoma, bringing the cohort to a total of 60 patients. This study represents the largest trial conducted to date in this rare tumor type. Epithelioid sarcoma is a soft tissue sarcoma characterized by loss of INI1. There are currently no approved systemic therapies for the treatment of patients with epithelioid sarcoma, and outcomes are extremely poor.

The synovial sarcoma arm of the Phase 2 trial has been fully enrolled. Although some patients remain on treatment, Epizyme has concluded that the activity of tazemetostat in this cohort is insufficient to continue further investigation of tazemetostat as a monotherapy. Unlike the cancers in the other four arms of the study, synovial sarcoma is characterized by a functional dysregulation of INI1, rather than by a complete loss of INI1.

Epizyme is now focusing its efforts on the four cohorts of INI1-negative tumors in its study, including the epithelioid sarcoma cohort. Enrollment continues in these cohorts and Epizyme plans to present data from the Phase 2 trial in the first half of 2017.

"The early clinical activity observed in the epithelioid sarcoma arm provides encouraging evidence of the effectiveness of EZH2 inhibition with tazemetostat in patients with INI1-negative tumors," added Peter Ho., M.D., Ph.D., chief medical officer, Epizyme. "The clinical experience observed so far in both the epithelioid sarcoma and synovial sarcoma cohorts is consistent with our Phase 1 experience for these cancers. We look forward to assessing clinical activity in the Phase 2 study and reporting data in the first half of 2017."

About the Tazemetostat Clinical Program
Tazemetostat, a first-in-class EZH2 inhibitor, is being evaluated as a monotherapy and in combination with other agents in multiple cancer indications. Phase 2 studies of tazemetostat as a monotherapy are currently ongoing in patients with non-Hodgkin lymphoma; in adults with INI1-negative tumors and children with certain genetically defined solid tumors, including INI1-negative tumors and synovial sarcoma; and in patients with mesothelioma characterized by BAP1 loss-of-function.

Additionally, tazemetostat is being evaluated in two combination studies in patients with DLBCL. A Phase 1b/2 trial of tazemetostat in combination with R-CHOP, an immuno-chemotherapy regimen consisting of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone, is being conducted as a front-line treatment for patients with DLBCL as part of Epizyme’s collaboration with the Lymphoma Study Association. A Phase 1b study evaluating tazemetostat in combination with Tecentriq (atezolizumab), an anti-PD-L1 cancer immunotherapy approved by the U.S. Food and Drug Administration, is being conducted as part of a collaboration with Genentech, a member of the Roche Group, in relapsed and refractory patients with DLBCL. For more information on tazemetostat clinical trials, please visit www.epizymeclinicaltrials.com.

On November 28, 2016 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) and Berlin-Chemie Menarini, a company of the Menarini Group, reported that both companies have entered into a global license agreement for PA799, class I PI3K inhibitor (Press release, Chugai, NOV 28, 2016, View Source [SID1234516809]).

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PA799 is the PI3K inhibitor originated by Chugai, which conducted phase I study for solid tumors in Europe. With its high selectivity for class I enzyme, the drug candidate showed a good safety profile in the clinical trial.

"We are pleased to sign a license agreement for PA799 with Menarini Group," said Chugai’s Representative Director, President and Chief Operating Officer, Tatsuro Kosaka. "PI3K is assumed to be one of the important kinases in the signaling pathway for the proliferation, the differentiation and the survival of tumor cells. We hope that the development of PA799 by Menarini Group will bring benefit to the patients as early as possible."

"We are excited about the opportunity to develop this anti-cancer agent, we believe in the mechanism of action of the PA799, and we are confident it will bring a great value to cancer patients in the world," said Reinhard Uppenkamp, Chief Executive Officer of Berlin-Chemie Menarini. "The scientific skills of Chugai and ability to conduct clinical trials and regulatory activities of Menarini Group will be in synergy for the future development of this product."

"We welcome the achievement of this strategic partnership with Chugai. This agreement allows us to add a key component in our portfolio, in fact, we make today a key step in the effort to expand the multimodal oncology pipeline of Menarini Group." said Lucia Aleotti, Chairman of Menarini Group.

Under the agreement, Chugai will grant Menarini Group an exclusive license for the manufacturing, development and marketing of PA799 worldwide. Under the terms of the agreement, Chugai will receive an upfront, milestone and royalty payments from Menarini Group.

On November 28, 2016 AVEO Oncology (NASDAQ:AVEO) reported that its development partner, EUSA Pharma, a specialty pharmaceutical company with a focus on oncology and oncology supportive care, has submitted its responses to the European Medicines Agency (EMA) Day 120 List of Questions (Press release, AVEO, NOV 28, 2016, View Source [SID1234516807]). The Day 120 List of Questions were issued by the Committee for Medicinal Products for Human Use (CHMP) as part of the centralized review process of the Marketing Authorization Application (MAA) for tivozanib for the first-line treatment of advanced renal cell carcinoma (RCC). The next step in the filing process, the EMA Day 180 List of Outstanding Issues, is expected in the first quarter of 2017.

“This submission represents an important step forward in working toward an anticipated first half 2017 European approval decision, one of three potential key tivozanib-related milestones during this period,” said Michael Bailey, president and chief executive officer of AVEO. “Given tivozanib’s unique activity and safety profile, we believe the first line RCC market in Europe represents a meaningful commercial opportunity, and we look forward to working with EUSA Pharma to fully elucidate this potential. In addition to a potential European approval decision, we expect to have initial results from the Opdivo combination TiNivo study in RCC and may see milestones from Ophthotech for tivozanib in acute macular degeneration in the first half of 2017.”