1stOncology™: Cancer Intelligence Service – Page 16300 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Kite Pharma Granted Access to Priority Medicines (PRIME) Regulatory Support for KTE-C19 in the Treatment of Chemorefractory Diffuse Large B-Cell Lymphoma (DLBCL)

On June 1, 2016 Kite Pharma, Inc. (Nasdaq:KITE) reported that the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) and Committee for Advanced Therapies (CAT) has granted access to its newly established Priority Medicines (PRIME) regulatory initiative for KTE-C19 in the treatment of patients with refractory diffuse large B-cell lymphoma (DLBCL) (Press release, Kite Pharma, JUN 1, 2016, View Source [SID:1234512941]). PRIME provides early and enhanced regulatory support to optimize regulatory applications and speed up the review of medicines that address a high unmet need. KTE-C19 is an investigational therapy in which a patient’s T-cells are genetically modified to express a chimeric antigen receptor (CAR) designed to target the antigen CD19, a protein expressed on the cell surface of B-cell lymphomas and leukemias.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

"We are honored to be among the first sponsors selected by the CHMP and CAT to participate in an innovative program that fosters development of therapies for patients with serious diseases that have no or only unsatisfactory therapeutic options," noted Arie Belldegrun, M.D., FACS, Chairman, President, and Chief Executive Officer of Kite. "The potential for KTE-C19 to address the substantial unmet medical need of patients with chemorefractory DLBCL is now recognized by designations from the U.S. and EU regulatory agencies. We look forward to working closely with the CHMP and CAT as we advance our multi-center ZUMA studies and move toward the KTE-C19 marketing authorization application process."

The U.S. Food and Drug Administration granted Breakthrough Therapy Designation to KTE-C19 for the treatment of patients with DLBCL, primary mediastinal B-cell lymphoma (PMBCL), and transformed follicular lymphoma (TFL) in December 2015.

About the Priority Medicines Initiative

Access to the Priority Medicines initiative is granted by the EMA to support the development and accelerate the review of new therapies to treat patients with unmet medical need. The criteria for the Priority Medicines initiative require early clinical evidence that the therapy offers a therapeutic advantage over existing treatments or benefits patients without treatment options. This designation provides appointment of a rapporteur, early dialogue and scientific advice at key development milestones, and the potential to qualify products for accelerated review earlier in the application process.

About Kite’s ZUMA Clinical Programs for KTE-C19

KTE-C19 is an investigational therapy in which a patient’s T-cells are genetically modified to express a CAR designed to target the antigen CD19, a protein expressed on the cell surface of B-cell lymphomas and leukemias. Kite is currently enrolling four pivotal studies (also known as ZUMA studies) for KTE-C19 in patients with various B-cell malignancies. In addition to the EMA Priority Medicines Designation, the U.S. Food and Drug Administration has granted Breakthrough Therapy Designation status to KTE-C19 for the treatment of patients with refractory diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), and transformed follicular lymphoma (TFL). KTE-C19 has also secured Orphan Drug Designation in the U.S. and the EU for DLBCL, PMBCL, follicular lymphoma (FL), mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), and acute lymphoblastic leukemia (ALL).

Study Phase Indication Status
ZUMA-1
NCT02348216 Phase 2 Pivotal
(N=112) Refractory DLBCL, PMBCL, TFL Phase 2 enrolling
ZUMA-2
NCT02601313 Phase 2 Pivotal
(N=70) Relapsed/refractory MCL Phase 2 enrolling
ZUMA-3
NCT02614066 Phase 1/2 Pivotal
(N=75) Relapsed/refractory Adult ALL Phase 1/2 enrolling
ZUMA-4
NCT02625480 Phase 1/2 Pivotal
(N=75) Relapsed/refractory Pediatric ALL Phase 1/2 enrolling

DLBCL = diffuse large B-cell lymphoma
PMBCL = primary mediastinal B-cell lymphoma
TFL = transformed follicular lymphoma
MCL = mantle cell lymphoma
ALL = acute lymphoblastic leukemia

Incyte and Moffitt Cancer Center Establish Multi-Year Oncology Research Alliance

On June 1, 2016 Incyte Corporation (Nasdaq: INCY) and Moffitt Cancer Center reported that they have entered into a research support and collaboration agreement, whereby Incyte has agreed to provide funding to conduct three new Moffitt Cancer Center research programs over a period of three years (Press release, Incyte, JUN 1, 2016, View Source [SID:1234512940]). The research programs will be focused on specific blood cancers, including myeloproliferative neoplasms (MPNs), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL) and chronic myelomonocytic leukemia (CMML). The objective of this alliance is to develop an improved understanding of basic cancer biology in the areas of focus, and interrogate specific therapeutic hypotheses involving Incyte’s proprietary small molecule therapeutics, both as single agents and in combination.

"Having access to Incyte’s diverse pipeline of targeted cancer therapies represents a unique and exciting opportunity for Moffitt researchers to expand our efforts to advance medical research in oncology and improve medical care for patients with cancer," said Jarett Rieger, Senior Director of Moffitt’s Office of Innovation and Industry Alliances and Associate General Counsel. "A huge strength of Moffitt is our ability to form inter-disciplinary research teams, and this exciting research alliance, involving numerous faculty members, is a testament to our team science culture."

Incyte will provide financial support for three research programs over the three year period of the collaboration.

"Incyte and Moffitt are both committed to improving the lives of patients with cancer through the discovery and development of novel medicines. This research alliance will enable new and important research into multiple blood cancers in a manner that both leverages and extends our current drug discovery efforts," stated Reid Huber, Ph.D., Incyte’s Chief Scientific Officer. "We are pleased to expand our growing network of academic collaborations and join forces with the world class investigators from Moffitt to advance the landscape of cancer treatment."

Portola Pharmaceuticals Announces Dosing of First Patient in Phase 2a Study of Cerdulatinib for Treatment of Hematologic Cancer and Upcoming Presentations of New Phase 1 Clinical Data at ASCO and EHA Annual Meetings

On June 01, 2016 Portola Pharmaceuticals Inc. (NASDAQ:PTLA), reported that it recently dosed the first patient in a Phase 2a study that is evaluating the safety and efficacy of cerdulatinib in patients with relapsed/refractory B-cell and T-cell malignancies who have failed multiple therapies (Press release, Portola Pharmaceuticals, JUN 1, 2016, View Source [SID:1234512916]). Cerdulatinib is an oral, dual Syk/JAK kinase inhibitor in development to treat patients with resistant or relapsed hematologic cancer. Cerdulatinib inhibits two key cell signaling pathways that promote cancer cell growth in certain hematologic malignancies.

Portola recently completed a Phase 1 study of cerdulatinib, which identified the maximum tolerated dose. Pharmacokinetic and pharmacodynamic outcomes data from the Phase 1 study will be presented in a poster session at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2016, which is taking place from June 3-7 in Chicago. Final results of the Phase 1 study, as well as data from two other cerdulatinib studies, will be presented in poster and e-poster sessions at the European Hematology Association (EHA) (Free EHA Whitepaper) 21st Annual Congress, which is taking place from June 9-12 in Copenhagen.

The cerdulatinib ASCO (Free ASCO Whitepaper) abstract is available at abstracts.asco.org and the EHA (Free EHA Whitepaper) abstracts are available at http://bit.ly/1U852D2. Details regarding the poster and e-poster presentations, which will include additional data not available in the abstracts, follow.

ASCO Annual Meeting 2016

Abstract Title (abstract #7557/poster board #113): Cerdulatinib (PRT062070): A dual SYK/JAK inhibitor in patients with relapsed/refractory b-cell malignancies — Pharmacokinetic and pharmacodynamic outcomes with twice-daily (BID) vs once-daily (QD) dosing
Presenting Author: Paul A. Hamlin, M.D., medical oncologist, Memorial Sloan Kettering Cancer Center
Poster Session Title: Hematologic Malignancies – Lymphoma and Chronic Lymphocytic Leukemia
Poster Presentation Date and Time: Monday, June 6, 8:00-11:30 a.m. Central Time
Location: McCormick Place, Hall A
EHA 21st Congress

Abstract Title (abstract #LB2252): Phase 1 final results and Phase 2a dose selection for cerdulatinib (PRT062070), a dual Syk/JAK inhibitor in patients with relapsed/refractory B-cell malignancies
Session Title: Chronic lymphocytic leukemia and related disorders — Clinical
E-poster Presentation Date and Time: Friday, June 10, 9:30 a.m.-Saturday, June 11, 7 p.m. CEST
E-Poster Location: Bella Center, Hall H

Abstract Title (abstract #E1017): Combined SYK and JAK inhibition by cerdulatinib induces apoptosis in CLL and overcomes resistance to ibrutinib
Session Title: Chronic lymphocytic leukemia and related disorders — Biology
E-poster Presentation Date and Time: Friday, June 10, 9:30 a.m.-Saturday, June 11, 7 p.m. CEST
Location: Bella Center, Hall H

Abstract Title (abstract #P590): The SYK/JAK inhibitor cerdulatinib shows promising in vitro activity in chronic lymphocytic leukemia
Session Title: Genomic complexity in CLL
Poster Presentation Date and Time: Saturday, June 11, 5:30-7:00 p.m. CEST
Location: Poster Area, Hall H

Nektar Therapeutics and Daiichi Sankyo Europe GmbH Sign European Licensing Agreement for ONZEALD™ (etirinotecan pegol), an Investigational Drug Candidate Being Developed to Treat Patients with Advanced Breast Cancer and Brain Metastases

On June 1, 2016 Nektar Therapeutics (Nasdaq: NKTR) reported that it has entered into an agreement with Daiichi Sankyo Europe for Nektar’s investigational drug therapy, ONZEALD (etirinotecan pegol, NKTR-102), which has completed a Phase 3 clinical trial (the BEACON study) in patients with advanced breast cancer (Press release, Nektar Therapeutics, JUN 1, 2016, View Source [SID:1234512915]). The agreement grants Daiichi Sankyo Europe exclusive rights to market ONZEALD in Europe (EEA), Switzerland and Turkey. Nektar Therapeutics will retain rights to ONZEALD in the United States and the rest of the world.

Under the terms of the agreement, Nektar Therapeutics is entitled to an upfront payment of $20 million as well as an additional $60 million in milestone payments, based upon the achievement of European regulatory milestones and European sales of ONZEALD. Nektar is also entitled to significant double-digit royalties on net sales in Europe.

"This new collaboration with Daiichi Sankyo Europe allows Nektar to advance ONZEALD to a potential conditional approval and availability in Europe as early as next year, and also enables us to retain ownership of the drug in the U.S. and rest of world," said Howard W. Robin, President and Chief Executive Officer of Nektar Therapeutics. "We are pursuing conditional approval for ONZEALD based on highly promising data from our Phase 3 BEACON clinical trial in the pre-specified subgroup of patients with advanced breast cancer who have a history of brain metastases. A diagnosis of brain metastases in women with advanced breast cancer is devastating and there are no therapies approved to treat this specific patient population."

Nektar plans to submit an MAA filing in June 2016 seeking conditional approval from the European Medicines Agency (EMA) for the use of ONZEALD in the treatment of patients with advanced breast cancer and brain metastases. On May 26, 2016, the Committee for Medicinal Products for Human Use (CHMP) granted an accelerated assessment procedure for the planned ONZEALD filing, which provides for an accelerated MAA review timeline.

Nektar will be responsible for sponsoring and funding the confirmatory trial which will support the Marketing Authorization Application (MAA) filing for ONZEALD in Europe. The data from the confirmatory trial can be used by Nektar for a potential U.S. new drug application (NDA) filing for ONZEALD.

Breast cancer is the most frequently diagnosed cancer in women worldwide with nearly 1.7 million new cases diagnosed in 2012.[1] There are approximately 250,000 newly-diagnosed cases of breast cancer in the United States and 470,000 in Europe each year. [1] Approximately 10-30 percent of patients with advanced breast cancer are also diagnosed with brain metastases. [2]

Nektar’s planned MAA filing is based upon data from a subgroup of patients from the completed BEACON study of single-agent ONZEALD in patients with advanced breast cancer. In this subgroup of 67 patients who also had a history of brain metastases, treatment with single-agent ONZEALD resulted in an improvement in median overall survival (OS) of 5.2 months compared to treatment with a single-agent chemotherapy of physician’s choice (TPC) (10 months vs. 4.8 months, P < 0.01). TPC included a choice of ixabepilone, vinorelbine, gemcitabine, eribulin or a taxane. In the planned primary analysis for the overall patient population in the BEACON study, ONZEALD median OS was 2.2 months longer than TPC (12.4 months vs. 10.3 months, P= 0.08).[3] In the overall patient population in the BEACON study, fewer patients in the ONZEALD arm had grade 3 or worse adverse events (AEs) than those in the TPC arm (204 [48%] vs. 256 [63%]; p < 0·0001).[3] The most common grade 3 and above AEs observed with ONZEALD were diarrhea (9.6%), neutropenia (9.6%), anemia (4.7%) and fatigue (4.5%). The most common grade 3 and above AEs observed with TPC were neutropenia (30.8%), anemia (4.7%), and dyspnea (4.4%).

In order to satisfy the EMA’s requirement for additional controlled data with the MAA for conditional approval, Nektar will sponsor a global, randomized Phase 3 trial of ONZEALD in approximately 350 patients with advanced breast cancer and brain metastases. The trial will compare ONZEALD to TPC and the primary endpoint in the trial will be OS. The trial will include a pre-specified interim analysis for OS which is to be conducted after 130 events have been observed in the trial. The U.S. Food and Drug Administration has also reviewed the Phase 3 study design with the Statistical Analysis Plan, and indicated the trial could serve as a potential registrational study by Nektar for purposes of seeking approval of ONZEALD to treat this patient population in the U.S.

The EMA may grant conditional marketing authorization when the potential treatment addresses a severely debilitating disease with an unmet medical need, has a positive benefit to risk profile, and the benefits to public health of its immediate availability outweigh the risks inherent in the fact that additional data are still required. Ongoing or new studies must be completed with the objective of confirming that the benefit to risk balance is positive. A conditional approval granted by the EMA is renewed on an annual basis until all obligations have been fulfilled, at which point a full approval may be granted by the EMA.

For additional terms and conditions of the licensing agreement between Nektar and Daiichi Sankyo Europe, please refer to the Current Report on Form 8-K filed today with the Securities and Exchange Commission.

About ONZEALD (etirinotecan pegol) (formerly NKTR-102)

ONZEALD is the first long-acting topoisomerase I inhibitor with an extended half-life and a unique structure that is designed to concentrate the drug in tumors. In patients, ONZEALD leads to greatly prolonged plasma SN38 exposure compared with irinotecan (elimination half-life of 37 days compared with 2 days) yet peak SN38 concentrations are at least 5- to 10-times less, which may also result in a favorable tolerability profile. ONZEALD was evaluated in a Phase 3, open-label, randomized, multicenter study (the BEACON study) that enrolled 852 women with locally recurrent or metastatic breast cancer, who have previously been treated with an anthracycline, taxane and capecitabine therapies.

ANTICANCER AGENT HALAVEN(R) APPROVED IN THE PHILIPPINES FOR NEW INDICATION FOR TREATMENT OF SOFT TISSUE SARCOMA SECOND COUNTRY IN ASIA AFTER JAPAN TO APPROVE HALAVEN FOR SOFT TISSUE SARCOMA

On June 1, 2016 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported that its subsidiary in the Philippines HI-Eisai Pharmaceutical Inc., has received approval for a new indication for its in-house discovered anticancer agent Halaven (eribulin mesylate) for the treatment of soft tissue sarcoma (Press release, Eisai, JUN 1, 2016, View Source [SID:1234512912]). Halaven is the first and only single agent to demonstrate a statistically significant overall survival (OS) benefit in a Phase III trial in patients with advanced, recurrent or metastatic soft tissue sarcoma (liposarcoma or leiomyosarcoma). The Philippines is the second country in Asia in which Halaven has been approved for the soft tissue sarcoma indication following approval in Japan, the United States and Europe.

In a Phase III study (Study 309)1 comparing the efficacy and safety of Halaven versus dacarbazine in patients with locally advanced, recurrent or metastatic soft tissue sarcoma (liposarcoma or leiomyosarcoma) who had disease progression following standard therapies which must have included an anthracycline and at least one other additional regimen, Halaven demonstrated a statistically significant extension in the study’s primary endpoint of OS over the comparator treatment dacarbazine. In this study, the most common treatment-emergent adverse events (incidence greater than or equal to 25%) in patients treated with Halaven were neutropenia, fatigue, alopecia, nausea, and peripheral neuropathy, which was consistent with the known side-effect profile of Halaven.

Soft tissue sarcoma is a collective term for a diverse group of malignant tumors that occur throughout the soft tissue (including fat, muscle, nerves, fibrous tissues and blood vessels). The worldwide annual incidence of soft tissue sarcoma is around 2-3 out of every 100,000 people. Halaven was approved for the treatment of patients with advanced soft tissue sarcoma in the United States, Japan and Europe in January, February and May 2016, respectively. Applications seeking approval for use in the treatment of soft tissue sarcoma are currently under review in countries and territories including Malaysia, Taiwan, Hong Kong, Singapore, and Thailand. Furthermore, Halaven has been designated as an orphan drug for soft-tissue sarcoma in the United States and Japan.

Halaven is a halichondrin class microtubule dynamics inhibitor with a distinct binding profile. Recent non-clinical studies showed that Halaven is associated with increased vascular perfusion and permeability in tumor cores.2 Halaven promotes the epithelial state and decreases the capacity of breast cancer cells to migrate. 3

Since the launch of Halaven as a treatment for breast cancer in the Philippines in August 2013, Eisai has been striving to further contribute to patients including obtaining additional approval in September 2014 for treatment of patients with locally advanced or metastatic breast cancer who have progressed after at least one chemotherapeutic regimen for advanced disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting, unless patients were not suitable for these treatments. Eisai Co., Ltd. No.16-38 June 1, 2016

Together with providing Halaven for patients with soft tissue sarcoma in the Philippines, Eisai is working to submit applications seeking approval for an indication covering soft tissue sarcoma throughout Asia. Furthermore, Eisai remains committed to maximizing the clinical value as well as exploring the potential clinical benefits of Halaven as it seeks to contribute further to addressing the diverse needs of, and increasing the benefits provided to, patients with cancer, their families, and healthcare providers.

About Halaven

Halaven is the first in the halichondrin class of microtubule dynamics inhibitors with a novel mechanism of action. Structurally Halaven is a simplified and synthetically produced version of halichondrin B, a natural product isolated from the marine sponge Halichondria okadai. Halaven is believed to work by inhibiting the growth phase of microtubule dynamics which prevents cell division. In addition, recent non-clinical studies showed that Halaven is associated with increased vascular perfusion and permeability in tumor cores.2 Halaven promotes the epithelial state and decreases the capacity of breast cancer cells to migrate.3

Halaven was first approved in November 2010 in the United States as a treatment for patients with metastatic breast cancer who have received at least two chemotherapeutic regimens for the treatment of metastatic disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting. Halaven is currently approved for use in the treatment of breast cancer in approximately 60 countries worldwide, including Japan and countries in Europe, the Americas and Asia. In Japan, Halaven has been approved to treat inoperable or recurrent breast cancer and was launched in the country in July 2011. In addition, Halaven has been approved in countries in Europe and Asia indicated as a treatment for patients with locally advanced or metastatic breast cancer who have progressed after at least one chemotherapeutic regimen for advanced disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting, unless patients were not suitable for these treatments.

Regarding soft tissue sarcoma, Halaven was approved in the United States for the treatment of patients with unresectable or metastatic liposarcoma who have received a prior anthracycline-containing regimen in January 2016, approved in Japan for the treatment of soft tissue sarcoma in February 2016, and approved in Europe for the treatment of adult patients with unresectable liposarcomas who have received prior anthracycline containing therapy (unless unsuitable) for advanced or metastatic disease in May 2016. Applications seeking approval for use in the treatment of soft tissue sarcoma are currently under review in Switzerland, Russia, Australia, Brazil, Malaysia, Taiwan, Hong Kong, Singapore, and Thailand. Furthermore, Halaven has been designated as an orphan drug for soft-tissue sarcoma in the United States and Japan.

About Soft Tissue

Sarcoma Soft tissue sarcoma is a collective term for a diverse group of malignant tumors that occur throughout the soft tissue (including fat, muscle, nerves, fibrous tissues and blood vessels). The worldwide annual incidence of soft tissue sarcoma is around 2-3 out of every 100,000 people. Approximately 12,000 patients in the United States and 29,000 patients in Europe are diagnosed with soft tissue sarcoma each year. According to a patient survey conducted by Japan’s Ministry of Health, Labour and Welfare, there are approximately 4,000 patients with soft tissue sarcoma in Japan. As the structures where the tumors originate are diverse, there are various types of soft tissue sarcoma, and the most common types include leiomyosarcoma, liposarcoma and malignant fibrous histiocytoma. While treatment of soft tissue sarcoma is focused on curative surgery, if the stage of the disease is advanced, treatment then becomes a combination of chemotherapy and radiation therapy. As outcomes are poor for patients with advanced disease, it remains a disease with significant unmet medical need.

About Study 3091

Conducted primarily in Europe and the United States, Study 309 was a multicenter, open-label, randomized Phase III study comparing the efficacy and safety of Halaven versus dacarbazine in 452 patients (aged 18 or over) with locally advanced, recurrent or metastatic soft tissue sarcoma (liposarcoma or leiomyosarcoma) who had disease progression following standard therapies which must have included an anthracycline and at least one other additional regimen. Patients received either Halaven (1.4 mg/m2 administered intravenously on Day 1 and Day 8) or dacarbazine (850–1200 mg/m2 administered intravenously on Day 1) every 21 days until disease progression.

From the results for the study, Halaven demonstrated a statistically significant extension in the study’s primary endpoint of overall survival (OS) over the comparator treatment dacarbazine (Halaven median OS: 13.5 months vs dacarbazine median OS: 11.5 months; Hazard Ratio (HR) 0.77 [95% CI=0.62-0.95], p=0.0169). Furthermore, in the study’s secondary endpoints, there was no statistically significant difference found between Halaven and dacarbazine in either progression-free survival (PFS) (median PFS: 2.6 months in both arms) or progression-free rate at 12 weeks (PFR12wks) (Halaven PFR12wks: 33% vs dacarbazine PFR12wks: 29%). In this study, the most common treatment-emergent adverse events (incidence greater than or equal to 25%) in patients treated with Halaven were neutropenia, fatigue, alopecia, nausea, and peripheral neuropathy, which was consistent with the known side-effect profile of Halaven.