On November 28, 2016 Curis, Inc. (Nasdaq:CRIS), a biotechnology company focused on the development and commercialization of innovative and effective drug candidates for the treatment of cancer, reported that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has granted full approval to Erivedge (vismodegib) for the treatment of adult patients with symptomatic metastatic basal cell carcinoma (BCC) or locally advanced BCC inappropriate for surgery or radiotherapy (Press release, Curis, NOV 28, 2016, View Source [SID1234516815]). Erivedge is also approved in the U.S. for the treatment of adults with metastatic basal cell carcinoma, or with locally advanced basal cell carcinoma that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation. Erivedge was developed and is marketed by Roche and Genentech, a member of the Roche Group, under a collaboration agreement between Curis and Genentech.

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Erivedge was originally granted ‘conditional approval’ in July, 2013 in the European Union (EU) and the authorization has now been converted from ‘conditional’ to ‘full approval’ based on the results from the STEVIE study that included 1215 patients with advanced BCC. STEVIE (MO25616) is a single-arm, open-label, Phase II, multicenter study that was conducted by Roche to assess the safety of vismodegib in patients with locally advanced and metastatic BCC. The safety and efficacy results of the STEVIE trial were consistent with the results of the pivotal study ERIVANCE BCC (SHH4476g) that supported the initial conditional approval of the drug in the EU.

About Basal Cell Carcinoma and the Hedgehog Pathway

According to the American Cancer Society, BCC accounts for approximately 80 percent of all diagnosed skin cancers. The disease is generally considered curable if the cancer is restricted to a small area of the skin. However, in a small group of people, if the disease is left untreated or recurs in the same location after surgery or radiotherapy, it may become locally advanced and invade further into surrounding areas such as sensory organs (ears, nose and eyes), bone, or other tissues. Depending on the location of the lesion, some cases of advanced BCC can be disfiguring, and treatment with surgery or radiation can lead to the loss of sensory organs and their functions such as eyesight or hearing. In a small proportion of patients, BCC can metastasize, spreading to other parts of the body. Abnormal signaling in the Hedgehog pathway is implicated in more than 90 percent of BCC cases.

About Erivedge

Erivedge is designed to selectively inhibit signaling in the Hedgehog pathway by binding to a protein called Smoothened. The Hedgehog signaling pathway plays an important role in regulating proper growth and development in the early stages of life and normally becomes less active in adults. The Hedgehog signaling pathway is implicated in the development of certain types of cancer, including BCC.

In January 2012, Erivedge became the first licensed medicine for patients with advanced basal cell carcinoma when the U.S. Food and Drug Administration (FDA) approved it under the priority review program that provides for an expedited six-month review of drugs that offer major advances in treatment. Erivedge is approved in the U.S. for the treatment of adults with metastatic basal cell carcinoma, or with locally advanced basal cell carcinoma that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation. Erivedge is currently approved and marketed in multiple countries worldwide.

Erivedge is currently in development by Roche and Genentech in other diseases including idiopathic pulmonary fibrosis and myelofibrosis.

About the Curis-Genentech Collaboration

Under the ongoing collaboration agreement between Genentech, a wholly owned member of the Roche Group, and Curis, Erivedge (vismodegib, GDC-0449, RG3616) was discovered by Genentech and was jointly validated by the parties through a series of preclinical studies. Pursuant to this collaboration, Genentech and Roche are responsible for clinical development, and Genentech (U.S.), Roche (Ex-U.S. excluding Japan) and Chugai Pharmaceuticals (Japan) are responsible for commercialization of Erivedge. Curis receives royalties on sales of Erivedge by Genentech/Roche.

On November 28, 2016 Merck (NYSE:MRK), known as MSD outside the United States and Canada, reported that the U.S. Food and Drug Administration (FDA) accepted for review the supplemental Biologics License Application (sBLA) for KEYTRUDA (pembrolizumab), the company’s anti-PD-1 therapy, for the treatment of previously treated patients with advanced microsatellite instability-high (MSI-H) cancer (Press release, Merck & Co, NOV 28, 2016, View Source [SID1234516812]). The FDA granted Priority Review with a PDUFA, or target action date, of March 8, 2017; the sBLA will be reviewed under the FDA’s Accelerated Approval program based on tumor response rate and durability of response. The FDA recently granted Breakthrough Therapy Designation to KEYTRUDA for unresectable or metastatic MSI-H non-colorectal cancer, and previously granted it for the treatment of patients with unresectable or metastatic MSI-H colorectal cancer.

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"The FDA’s acceptance of this application represents an important advance for the field of immuno-oncology and is further evidence of Merck’s commitment to identifying patients most likely to benefit from KEYTRUDA treatment," said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. "We believe that patients whose tumors harbor DNA repair defects may be especially responsive to KEYTRUDA, and we look forward to working with the FDA to bring this important new therapy to these very challenging treatment situations."

The application, which is seeking approval for KEYTRUDA at a fixed dose of 200 mg every three weeks, is based on data from five uncontrolled, open-label, multi-cohort, multi-site phase I/II trials investigating the activity of KEYTRUDA in MSI-H cancer.

About Microsatellite Instability

Microsatellites are short repetitive sequences of DNA found throughout the genome. Microsatellite instability – or MSI – is caused by a deficiency in the cell’s ability to repair errors in the DNA sequence (mismatch repair) that occur during cell division leading to a characteristic change in microsatellite repeats. MSI-H is already an established biomarker in certain types of cancer. The presence of MSI is generally determined by an analytical test that compares the length of DNA from several microsatellite markers in tumor and normal cells, and produces a hallmark profile that distinguishes MSI-high, MSI-low, or microsatellite-stable tumor samples.

About KEYTRUDA (pembrolizumab)

KEYTRUDA is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

KEYTRUDA is administered as an intravenous infusion over 30 minutes every three weeks for the approved indications. KEYTRUDA for injection is supplied in a 100 mg single use vial.

KEYTRUDA Indications and Dosing

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma at a dose of 2 mg/kg every three weeks until disease progression or unacceptable toxicity.

Lung Cancer

KEYTRUDA is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression [tumor proportion score (TPS) ≥50%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA is also indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA (pembrolizumab).

In metastatic NSCLC, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Head and Neck Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. In HNSCC, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Selected Important Safety Information for KEYTRUDA (pembrolizumab)

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 94 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%) pneumonitis, and occurred more frequently in patients with a history of prior thoracic radiation (6.9%) compared to those without (2.9%). Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 48 (1.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%) colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 19 (0.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%) hepatitis. Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

KEYTRUDA (pembrolizumab) can cause hypophysitis. Hypophysitis occurred in 17 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%) hypophysitis. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2; withhold or discontinue for Grade 3 or 4 hypophysitis.

KEYTRUDA can cause thyroid disorders, including hyperthyroidism, hypothyroidism, and thyroiditis. Hyperthyroidism occurred in 96 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.8%) and 3 (0.1%) hyperthyroidism. Hypothyroidism occurred in 237 (8.5%) of 2799 patients receiving KEYTRUDA, including Grade 2 (6.2%) and 3 (0.1%) hypothyroidism. The incidence of new or worsening hypothyroidism was higher in patients with HNSCC occurring in 28 (15%) of 192 patients with HNSCC, including Grade 3 (0.5%) hypothyroidism. Thyroiditis occurred in 16 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.3%) thyroiditis. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer replacement hormones for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism.

KEYTRUDA can cause type 1 diabetes mellitus, including diabetic ketoacidosis, which have been reported in 6 (0.2%) of 2799 patients. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 9 (0.3%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis.

KEYTRUDA can cause other clinically important immune-mediated adverse reactions. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA (pembrolizumab) when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients: arthritis (1.5%), exfoliative dermatitis, bullous pemphigoid, rash (1.4%), uveitis, myositis, Guillain-Barré syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, and partial seizures arising in a patient with inflammatory foci in brain parenchyma.

KEYTRUDA can cause severe or life-threatening infusion-related reactions, which have been reported in 6 (0.2%) of 2799 patients. Monitor patients for signs and symptoms of infusion-related reactions, including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of KEYTRUDA.

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). Adverse reactions leading to interruption of KEYTRUDA occurred in 21% of patients; the most common (≥1%) was diarrhea (2.5%). The most common adverse reactions with KEYTRUDA vs ipilimumab were fatigue (28% vs 28%), diarrhea (26% with KEYTRUDA), rash (24% vs 23%), and nausea (21% with KEYTRUDA). Corresponding incidence rates are listed for ipilimumab only for those adverse reactions that occurred at the same or lower rate than with KEYTRUDA.

In KEYNOTE-002, KEYTRUDA was discontinued due to adverse reactions in 12% of 357 patients with advanced melanoma; the most common (≥1%) were general physical health deterioration (1%), asthenia (1%), dyspnea (1%), pneumonitis (1%), and generalized edema (1%). Adverse reactions leading to interruption of KEYTRUDA occurred in 14% of patients; the most common (≥1%) were dyspnea (1%), diarrhea (1%), and maculopapular rash (1%). The most common adverse reactions with KEYTRUDA vs chemotherapy were fatigue (43% with KEYTRUDA (pembrolizumab)), pruritus (28% vs 8%), rash (24% vs 8%), constipation (22% vs 20%), nausea (22% with KEYTRUDA), diarrhea (20% vs 20%), and decreased appetite (20% with KEYTRUDA). Corresponding incidence rates are listed for chemotherapy only for those adverse reactions that occurred at the same or lower rate than with KEYTRUDA.

KEYTRUDA was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC. The most common adverse event resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.8%). Adverse reactions leading to interruption of KEYTRUDA occurred in 23% of patients; the most common (≥1%) were diarrhea (1%), fatigue (1.3%), pneumonia (1%), liver enzyme elevation (1.2%), decreased appetite (1.3%), and pneumonitis (1%). The most common adverse reactions (occurring in at least 20% of patients and at a higher incidence than with docetaxel) were decreased appetite (25% vs 23%), dyspnea (23% vs 20%), and nausea (20% vs 18%).

KEYTRUDA was discontinued due to adverse reactions in 17% of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. The most common adverse reactions (reported in at least 20% of patients) were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were generally similar to those occurring in patients with melanoma or NSCLC, with the exception of increased incidences of facial edema (10% all Grades; 2.1% Grades 3 or 4) and new or worsening hypothyroidism.

It is not known whether KEYTRUDA is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA and for 4 months after the final dose.

Safety and effectiveness of KEYTRUDA have not been established in pediatric patients.

Our Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, helping people fight cancer is our passion and supporting accessibility to our cancer medicines is our commitment. Our focus is on pursuing research in immuno-oncology and we are accelerating every step in the journey – from lab to clinic – to potentially bring new hope to people with cancer.

As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the fastest-growing development programs in the industry. We are currently executing an expansive research program that includes more than 360 clinical trials evaluating our anti-PD-1 therapy across more than 30 tumor types. We also continue to strengthen our immuno-oncology portfolio through strategic acquisitions and are prioritizing the development of several promising immunotherapeutic candidates with the potential to improve the treatment of advanced cancers.

For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

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.