On March 30, 2017 Ignyta, Inc. (Nasdaq: RXDX), a biotechnology company focused on precision medicine in oncology, reported data demonstrating the successful treatment with entrectinib – Ignyta’s investigational, orally available, CNS-active tyrosine kinase inhibitor targeting tumors that harbor TRK, ROS1 or ALK fusions – of a patient with a primary brain tumor harboring an NTRK1 fusion (Press release, Ignyta, MAR 30, 2017, View Source [SID1234518323]). Schedule your 30 min Free 1stOncology Demo! The study, exploring genetic alterations associated with glioneuronal tumors, was led by researchers at Massachusetts General Hospital and was published in Precision Oncology. Researchers discovered novel oncogenic fusions involving members of the NTRK gene family in three out of 26 patients evaluated, and reported that in a patient with a BCAN-NTRK1 fusion, treatment with entrectinib resulted in a 60 percent regression in tumor size and the resolution of clinical symptoms that was maintained for 11 months on treatment. Entrectinib is currently being studied in a registration-enabling Phase 2 clinical trial known as STARTRK-2.
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"We are pleased to see the CNS activity of entrectinib demonstrated in this peer-reviewed publication in Precision Oncology, which highlights the need for CNS-active compounds to effectively treat CNS neoplasms, as well as other solid tumors with a propensity to metastasize to the brain," said Jonathan Lim, M.D., Chairman and CEO of Ignyta. "This robust activity of entrectinib in a patient with a primary brain tumor builds on the rapid and durable anti-tumor activity we’ve seen with this compound across other TRK, ROS1, or ALK solid tumors across multiple histologies and complements the 71% RECIST ORR (five out of seven patients) demonstrated in patients with extracranial tumors that had metastasized to the brain in our Phase 1 studies. Entrectinib is the only TRK inhibitor to have demonstrated RECIST responses in patients with CNS disease and the only TRK inhibitor to have a peer-reviewed publication on its activity in primary brain tumors."
Data presented in the study characterized a cohort of 26 glioneuronal tumors, which identified, through in-depth genomic analysis, BRAF mutations in 34 percent of tumors and oncogenic fusions in 30 percent of tumors. Further, researchers identified three tumors in the cohort that contained fusions involving members of the NTRK gene family, including one patient harboring a BCAN-NTRK1 fusion. Based on previous clinical results, therapeutic intervention for the patient harboring the NTRK1 fusion was pursued, and entrectinib was selected due to its CNS activity. Following subtotal surgical resection and confirmation of the tumor’s specific genetic alteration, the patient was enrolled in the Phase 1 dose-escalation trial of entrectinib (NCT02097810). The patient received entrectinib daily for 11 months and experienced lower extremity edema as the only documented side effect related to therapy. Analysis after nine months of treatment showed a 60 percent reduction in the size of the tumor, as well as improvement in vision-related symptoms. The patient was taken off of treatment after 11 months due to a gradual worsening of vision and tumor size. Based on the results of the study, we believe NTRK fusions should be considered an actionable target for glioneuronal tumor treatment.
Phase II Study of Daratumumab in Non-Hodgkin’s Lymphoma Will Not Proceed to Stage 2 of Trial
On March 30, 2017 Genmab A/S (Nasdaq Copenhagen: GEN) reported that its collaboration partner for daratumumab, Janssen Biotech, Inc., has decided not to initiate stage 2 of the Phase II study (CARINA, LYM2001) of daratumumab in three types of relapsed or refractory non-Hodgkin’s lymphoma (NHL) (Press release, Genmab, MAR 30, 2017, View Source [SID1234518322]). The study will not proceed to stage 2 as a data review showed that two cohorts of the study, investigating the use of daratumumab monotherapy in relapsed or refractory patients with follicular lymphoma (FL), and with diffuse large B-cell lymphoma (DLBCL) did not reach the predefined futility thresholds of overall response rates (ORR) of 50%, and 30%, respectively. In the third cohort in the study, patients with mantle cell lymphoma (MCL), ORR was not evaluable due to slow recruitment, driven by the aggressive nature of the disease in its final stages. This has no impact on other ongoing or planned studies with daratumumab.
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"While we hoped that daratumumab as a monotherapy could potentially provide a new treatment option in NHL patients with a high unmet medical need, the preliminary activity profile seen was not sufficient for the study to continue. Daratumumab is still being investigated in a number of indications including multiple myeloma and other hematological cancers such as NK/T-cell lymphoma and myelodysplastic syndrome as well as in solid tumors," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.
About the CARINA LYM2001 study
The Phase II study (NCT02413489) is a three arm (DLBCL, FL, MCL), open-label multicenter study, which planned to enroll up to 210 patients in 2 stages with relapsed or refractory non-Hodgkin’s lymphoma. Stage 1 of the study was designed to provide a preliminary assessment of monotherapy activity, with stage 2 designed to further evaluate safety and efficacy of daratumumab monotherapy. Stage 2 will now not proceed. The primary endpoint of the study was overall response rate. The safety profile of daratumumab in these diseases was also assessed.
About DARZALEX (daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.1 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe for use as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. For more information, visit www.DARZALEX.com.
Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).1,2,3,4,5
Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. Five Phase III clinical studies with daratumumab in relapsed and frontline multiple myeloma settings are currently ongoing, and additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant diseases on which CD38 is expressed, such as smoldering myeloma, NK/T-cell lymphoma, amyloidosis, myelodysplastic syndromes and solid tumors. Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA, for multiple myeloma, as both a monotherapy and in combination with other therapiesa
Curis to Present Preclinical Data on IRAK4 Kinase Inhibitor CA-4948 at AACR Annual Meeting
On March 30, 2017 Curis, Inc. (Nasdaq:CRIS), a biotechnology company focused on the development and commercialization of innovative and effective drug candidates for the treatment of human cancers, reported that Curis scientists will present data from its IRAK4 kinase inhibitor development candidate, CA-4948, at the Annual Meeting of American Association of Cancer Research (AACR) (Free AACR Whitepaper) to be held April 1 — 5, 2017 in Washington, D.C (Press release, Curis, MAR 30, 2017, View Source [SID1234518321]). Curis has exclusive license to CA-4948 under a collaboration agreement with Aurigene established in 2015. Schedule your 30 min Free 1stOncology Demo! Additional information follows. Abstracts can be accessed at www.aacr.org.
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Poster Presentation
Date/Time: Monday, Apr. 3, 2017, 8:00 AM – 12:00 PM
Session Title: Novel Molecular Targets 1
Session Category: Experimental and Molecular Therapeutics
Presentation Title: Efficacy of the IRAK4 Inhibitor CA-4948 in Patient-Derived Xenograft Models of
Diffuse Large B Cell Lymphoma
Abstract Number: 1168
Jazz Pharmaceuticals and Nippon Shinyaku Enter Into License Agreements for the Development and Commercialization of Defitelio and Vyxeos in Japan
On March 30, 2017 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported that it has entered into license agreements with Nippon Shinyaku, Co., Ltd. for Defitelio (defibrotide sodium) and Vyxeos (cytarabine and daunorubicin liposome injection), or CPX-351, in Japan (Press release, Jazz Pharmaceuticals, MAR 30, 2017, View Source [SID1234518312]). Schedule your 30 min Free 1stOncology Demo! Under the terms of the agreements, Nippon Shinyaku will receive exclusive rights to develop and commercialize Defitelio and Vyxeos in Japan in return for an upfront payment to Jazz Pharmaceuticals and subsequent payments based on the successful achievement of certain regulatory and commercial milestones. Jazz Pharmaceuticals will manufacture and supply Defitelio and Vyxeos to Nippon Shinyaku, and will receive revenue based on a percentage of product sales in Japan. Financial terms of the agreement have not been disclosed. Commercialization of Defitelio and Vyxeos in Japan is subject to regulatory approval in Japan.
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"We are pleased to have Nippon Shinyaku as our strategic partner in Japan," said Iain McGill, senior vice president, Jazz Pharmaceuticals Europe and rest of world. "Nippon Shinyaku’s expertise and focus in hematology/oncology make them an outstanding partner to bring Defitelio and Vyxeos to patients with significant unmet medical needs in Japan."
About Defitelio
Defitelio received marketing approval in the U.S. in 2016 for the treatment of adult and pediatric patients with hepatic veno-occlusive disease (VOD), with renal or pulmonary dysfunction following hematopoietic stem-cell transplantation (HSCT). In 2013, the European Commission granted marketing authorization to Defitelio under exceptional circumstances for the treatment of severe VOD in patients undergoing HSCT therapy. HSCT is an aggressive, potentially curative procedure to treat patients with malignant and non-cancerous hematologic disorders such as leukemia, lymphoma and aplastic anemia, and congenital immunodeficiency and autoimmune disorders. VOD is a rare and potentially life-threatening complication of HSCT affecting the sinusoidal endothelial cells of the liver, which occurs in approximately 9-14% of HSCT patients.1,2 Defibrotide is also being investigated in a global Phase 3 randomized study (NCT02851407) for the prevention of hepatic VOD in high risk adult and pediatric patients undergoing HSCT. Defibrotide is currently an investigational drug in Japan and the Defitelio trade name has not been approved.
About Vyxeos (CPX-351)
Vyxeos, or CPX-351, is an investigational product being evaluated for the treatment of AML and is a combination of the antineoplastic agents cytarabine and daunorubicin encapsulated within a nano-scale liposome at a 5:1 molar ratio. The proposed trade name, Vyxeos, is conditionally approved by the U.S. Food and Drug Administration (FDA) and is subject to confirmation upon approval of the New Drug Application (NDA). Data from the pivotal Phase 3 study, which met its primary endpoint, were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in June 2016. Jazz Pharmaceuticals has initiated a rolling NDA submission to the FDA with expected completion of the submission by the end of March 2017. A Marketing Authorization Application to the European Medicines Agency is planned for the second half of 2017. There have been no studies with CPX-351 in Japan, and the Vyxeos trade name has not been approved.
10-K/A [Amend] – Annual report [Section 13 and 15(d), not S-K Item 405]
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