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Seattle Genetics Initiates Phase 1 Trial of SGN-CD19B for Patients with B-cell Non-Hodgkin Lymphoma

On February 25, 2016 Seattle Genetics, Inc. (Nasdaq: SGEN) reported initiation of a phase 1 clinical trial of SGN-CD19B for relapsed or refractory patients with two subtypes of B-cell non-Hodgkin lymphoma (NHL): diffuse large B-cell lymphoma (DLBCL) and grade 3 follicular lymphoma (Press release, Seattle Genetics, FEB 25, 2016, View Source [SID:1234509210]).

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About 85 percent of NHL is of B-cell lineage, and CD19 is broadly expressed across all subtypes of B-cell malignancies. SGN-CD19B is a novel antibody-drug conjugate (ADC) targeted to CD19 utilizing Seattle Genetics’ newest ADC technology. SGN-CD19B is composed of an anti-CD19 antibody attached to a highly potent cytotoxic DNA-crosslinking agent called a pyrrolobenzodiazepine (PBD) dimer, via a proprietary site-specific conjugation technology to a monoclonal antibody with engineered cysteines (EC-mAb). The trial is designed to assess the safety and antitumor activity of SGN-CD19B.

"B-cell malignancies are the most common type of non-Hodgkin lymphoma, or NHL. In the relapsed or refractory disease setting, B-cell NHL is difficult to treat, and there is an urgent need to identify more effective treatment options for these patients," said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. "With SGN-CD19A and SGN-CD19B, we are evaluating two clinical-stage ADCs directed against CD19 utilizing different ADC technologies with distinct mechanisms of action, which may result in differentiated clinical profiles and utility in NHL. Together with ADCETRIS, these programs are a part of our extensive efforts to improve outcomes for patients with lymphoma."

The study is a phase 1, open-label, multi-center, dose-escalation clinical trial. The primary endpoints are the estimation of the maximum tolerated dose and evaluation of the safety of SGN-CD19B. In addition, the trial will evaluate antitumor activity, pharmacokinetics, objective response rate and progression-free survival. The study is designed to evaluate SGN-CD19B administered every four or six weeks and will enroll up to approximately 100 relapsed or refractory patients at multiple centers in the United States.

Preclinical data presented at the 2015 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting demonstrated that SGN-CD19B exhibits antitumor activity against a broad panel of CD19-expressing B-cell malignancies, inducing durable tumor regressions in multiple preclinical models of NHL and B-ALL.

With more than 15 years of experience and innovation, Seattle Genetics is the leader in developing ADCs. ADCs are monoclonal antibodies that are designed to selectively deliver cell-killing agents to tumor cells. This approach is intended to spare non-targeted cells and, thus, reduce many of the toxic effects of traditional chemotherapy while enhancing antitumor activity.

For more information about the trial, including enrolling centers, please visit www.clinicaltrials.gov.

About Non-Hodgkin Lymphoma

Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma (NHL). NHL is further categorized into indolent (low-grade) or aggressive lymphomas, including DLBCL and grade 3 follicular lymphoma. DLBCL is the most common type of NHL. According to the American Cancer Society, more than 72,000 cases of NHL will be diagnosed in the United States during 2016 and more than 20,000 people will die from the disease.

About SGN-CD19B

SGN-CD19B is a novel ADC targeted to CD19 utilizing Seattle Genetics’ newest ADC technology. CD19 is a protein expressed broadly on normal and malignant B-cells. SGN-CD19B is an antibody-drug conjugate (ADC) composed of an anti-CD19 antibody attached to two molecules of a highly potent DNA crosslinking agent called a pyrrolobenzodiazepine (PBD) dimer, using Seattle Genetics’ proprietary technology. PBD dimers are significantly more potent than systemic chemotherapeutic drugs, and site-specific conjugation technology (EC-mAb) allows uniform drug-loading of the cell-killing PBD dimer to the anti-CD19 antibody. The ADC is designed to be stable in the bloodstream and to release its potent DNA binding agent upon internalization into CD19-expressing cells. The ADC technology used in SGN-CD19B is the same as vadastuximab talirine (SGN-CD33A; 33A), an ADC in clinical development for myeloid malignancies.

Peregrine Pharmaceuticals Provides Update on Phase III SUNRISE Trial of Bavituximab

On February 25, 2016 Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM) (NASDAQ:PPHMP), a biopharmaceutical company focused on developing therapeutics to stimulate the body’s immune system to fight cancer, reported that it is discontinuing the company’s Phase III SUNRISE trial of bavituximab in patients with previously treated locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) (Press release, Peregrine Pharmaceuticals, FEB 25, 2016, View Source [SID:1234509207]).

The decision to stop the trial was based on the recommendation of the study’s Independent Data Monitoring Committee (IDMC) following a pre-specified interim analysis performed after 33% of targeted overall events (patient deaths) in the study were reached. Results of the analysis demonstrated that the bavituximab plus docetaxel group did not show a sufficient improvement in overall survival as compared to the docetaxel group to warrant continuation of the study. The interim analysis showed that the bavituximab combination group is performing as expected according to the original trial assumptions in terms of overall survival, while the docetaxel group is dramatically outperforming overall survival expectations based on the original trial assumptions and as compared to recently published studies.

"Let me start by taking this opportunity to thank all of the patients, their families, and the physicians who participated in the SUNRISE trial. While we are deeply disappointed by this early outcome from the SUNRISE trial, we plan to take a deliberate and detailed approach in reviewing and verifying all available data from the trial in order to understand what subgroups or other patient characteristics may have impacted the performance of the study. While we perform this analysis, we plan to put our other chemotherapy combination studies on hold until we have a clear understanding of the SUNRISE study results," said Steven W. King, president and chief executive officer of Peregrine. "While this is an unexpected and disappointing setback for the bavituximab chemotherapy combination clinical program, we have not seen anything in this trial result that diminishes our enthusiasm for advancing our immuno-oncology (I-O) combination trials. The I-O combination studies are based on different mechanistic synergies that are clearly separate from the chemotherapy combination being evaluated in the SUNRISE study. In addition, it is important to note that in no way do these results have any impact on our contract manufacturing business conducted through our wholly owned subsidiary, Avid Bioservices. This business has shown consistent revenue growth and has been instrumental in maintaining a strong cash position and our plan is to continue growing this business."

As of February 1, 2016, Avid Bioservices had a revenue backlog in excess of $58 million under committed contracts from existing clients. In addition, Peregrine had $67.5 million in cash and equivalents as of January 31, 2016.

About Bavituximab: A Targeted Investigational Immunotherapy
Bavituximab is an investigational chimeric monoclonal antibody that targets phosphatidylserine (PS). Signals from PS inhibit the ability of immune cells to recognize and fight tumors. Bavituximab is believed to override PS mediated immunosuppressive signaling by blocking the engagement of PS with its receptors as well as by sending an alternate immune activating signal. PS targeting antibodies have been shown to shift the functions of immune cells in tumors, resulting in multiple signs of immune activation and robust anti-tumor immune responses.

Foundation Medicine Announces First-Ever Public Release of Broad Pediatric Data From FoundationCORE™ to Accelerate the Development of Precision Medicine Strategies for Pediatric Cancers

On February 25, 2016 Foundation Medicine, Inc. (NASDAQ:FMI) reported that the company will release to the public molecular profiles of pediatric cancers currently maintained as part of FoundationCore, the company’s information knowledgebase (Press release, Foundation Medicine, FEB 25, 2016, View Source [SID:1234509199]). FoundationCORE is one of the largest and most robust collections of common and rare clinical tumor profiles globally. The release of this data is part of the company’s ongoing effort to stimulate and accelerate research and development of much needed precision oncology therapies to treat all cancers, including pediatric cancers. The announcement of the data release, which is the first-of-its-kind from FoundationCORE, was announced today at the Precision Medicine Initiative Summit held at the White House.

"One of the biggest impediments to progress in the field of childhood cancer is the paucity of genomic data available from patients at the time of disease relapse. These data are critical to defining comprehensive strategies to precisely treat relapsed disease, and more importantly, to prevent disease recurrence in the first place," stated John M. Maris, M.D., Giulio D’Angio Endowed Professor of Pediatric Oncology at Children’s Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania. "The data being made available from Foundation Medicine will serve as a tremendous resource for the cancer research community and should catalyze the process of bringing effective new therapies to children with cancer."

FoundationCORE is a molecular information knowledgebase that contains genomic information and insights from more than 68,000 adult and pediatric patients whose tumors were profiled by Foundation Medicine. FoundationCORE is continuously evolving over time, informed by every new tumor sequenced with the company’s clinical comprehensive genomic profiling assays, FoundationOne and FoundationOne Heme. Foundation Medicine is developing a web-based HIPPA-compliant portal for public access to the de-identified, molecular-level pediatric tumor information contained in FoundationCORE. The portal is expected to be accessible for public access by March 31st.

"The proposed release of data by Foundation Medicine is a major advance towards achieving our nation’s precision medicine initiatives, particularly in an area of significant unmet need for children," said Nancy Goodman, executive director, Kids v Cancer. "This type of out-of-the-box initiative gives great hope to the families and patients who need it most. We’re looking forward to the renaissance in targeted and immunotherapies for children that may come as a result of this data."

Pediatric cancers are a rare and diverse collection of diseases. While childhood and adolescent cancer is rare, it remains the leading cause of death by disease among children. The American Cancer Society predicted that about 10,380 children in the United States would be diagnosed with cancer in 2015 and childhood cancer rates have been rising slightly for the past few decades.1 The data set being released from FoundationCORE offers robust opportunities for researchers, and can be used to generate hypotheses, validate rare findings and investigate the genomic landscape of rare tumors for which only small studies exist. Data from thousands of tumors will be publicly available without cost to the research community for exploration and incorporation into future experiments that will ultimately improve the treatment and prognosis for children with cancer.

"There are few things in life as devastating as when a child is diagnosed with cancer. It’s critically important to the achievement of our corporate mission that the robust genomics information we have amassed is freely and easily accessible to researchers and utilized as an important tool to address the significant unmet medical need in pediatric cancers," said Michael Pellini, M.D., chief executive officer, Foundation Medicine. "We are extremely proud to be in a position that enables us to foster global collaborations among researchers by providing anywhere, anytime access to rich molecular information in an easy to use format. In doing so, we hope to accelerate the pace of innovation in pediatric cancer with the intent of bringing new, potentially lifesaving therapeutics to children."

Baxalta and Precision BioSciences form Global Genome Editing Collaboration in Immuno-Oncology

On February 25, 2016 Baxalta Incorporated (NYSE: BXLT), a global biopharmaceutical leader dedicated to delivering transformative therapies to patients with orphan diseases and underserved conditions, and Precision BioSciences, the genome editing company, reported a global collaboration to develop a broad series of allogeneic chimeric antigen receptor (CAR) T cell therapies directed towards areas of major unmet need in multiple cancers (Press release, Baxalta, FEB 25, 2016, View Source [SID:1234509194]).

CAR T is widely recognized as a breakthrough technology with the potential to become a curative option for certain malignancies. Most CAR T cell therapy technologies isolate cells from cancer patients’ blood and re-engineer them to specifically target receptors on tumor cells. The reprogrammed cells are multiplied in a laboratory and then returned to the patient to target the tumor. This approach has had initial success in clinical trials for certain tumor types, but persistent scaling challenges remain based on the highly personalized nature of the therapy. Precision BioSciences’ proprietary ARCUS genome editing technology enables the production of CAR T cells derived from healthy donors rather than relying on the patient. This approach aims to overcome the manufacturing-related limitations with existing CAR T therapies and enable a broader range of malignancies to be targeted.

"Collaborating with Precision BioSciences enables Baxalta to accelerate innovation in immuno-oncology with a next-generation, donor-derived CAR T strategy using a proprietary combination of genome editing expertise and technology," said David Meek, executive vice president and president, Oncology, Baxalta. "Combining Precision BioSciences’ ARCUS technology with Baxalta’s global infrastructure, expertise and growing immuno-oncology portfolio is a synergistic approach that we believe has the potential to make disruptive approaches available to people with a range of underserved cancers."

"Baxalta is an ideal partner in CAR T for Precision and our ARCUS genome editing platform because of their global reach, collaborative business model, and long-term commitment to succeeding in immuno-oncology," said Matthew Kane, CEO of Precision BioSciences. "We look forward to working closely with the team at Baxalta to develop novel CAR T therapeutics that could transform the treatment of cancer."

Under the terms of the agreement, Baxalta and Precision BioSciences will develop CAR T therapies for up to six unique targets, with the first program expected to enter clinical studies in late 2017. Precision BioSciences will be responsible for performing early-stage research activities up to Phase 2, following which Baxalta has the exclusive right to opt in for late-stage development and commercialization. Precision BioSciences will receive an upfront payment of $105 million from Baxalta, with additional option fees, developmental, clinical, regulatory, and sales milestones, potentially totaling up to $1.6 billion, in addition to royalties on worldwide sales. Precision also has the right to participate in the development and commercialization of any licensed products resulting from the collaboration through a 50/50 co-development and co-promotion option in the United States. Additional terms and initial targets were not disclosed.

The agreement follows another recently established Baxalta collaboration to advance novel therapeutics against checkpoint targets, advancing the company’s strategic commitment to investing in immuno-oncology and building an innovative portfolio of cancer immunotherapies.

Acalabrutinib recommended for orphan drug designation in Europe for three indications

On February 25, 2016 AstraZeneca and Acerta Pharma BV, a company in which AstraZeneca has a majority equity investment, reported that the European Medicines Agency (EMA) Committee for Orphan Medicinal Products (COMP) adopted three positive opinions recommending acalabrutinib (ACP-196) for designation as an orphan medicinal product (Press release, AstraZeneca, FEB 25, 2016, View Source [SID:1234509186]). The three positive opinions are for the treatment of chronic lymphocytic leukaemia (CLL) / small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL) and lymphoplasmacytic lymphoma (Waldenström’s macroglobulinaemia, MG).

Sean Bohen, Executive Vice-President of Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "Today’s three positive opinions recommending acalabrutinib for designation as an orphan medicinal product are important milestones. They reinforce the strategic rationale for our investment in Acerta, demonstrating clear progress in developing a potential best-in-class medicine that could transform treatment for patients across a range of blood cancers. The positive opinions underscore the continued need for the development of new therapies in these serious and life-threatening conditions and support our commitment to bring new medicines to patients as quickly as possible."

CLL is a slow-growing blood and bone marrow cancer that accounts for approximately one in four cases of leukaemia.i,ii Most CLL patients experience disease progression despite initial response to therapy and may require additional treatment. iii SLL is a clinically similar disease localized to the lymph nodes.iv

MCL is an aggressive non-Hodgkin’s lymphoma (NHL) typically associated with very poor outcomes.v MCL represents around 5% of all NHLs.vi The name comes from the fact that the tumour cells originate in the mantle zone of the lymph node. vi

WM is a rare, slow-growing cancer predominantly affecting older individuals, with a mean age of 60 at diagnosis.vii, viii and median survival from five to nearly eleven years. vii, viii

The COMP adopts an opinion on Orphan Drug Designation, after which the opinion is submitted to the European Commission (EC) for endorsement. Orphan Drug Designation is a status assigned to a medicine intended for use in rare diseases.ix To be granted orphan status by the EC, a medicine must be intended for the treatment, prevention or diagnosis of a disease that is life threatening and has a prevalence of up to five in 10,000 in the European Union. Additionally, the intended medicine must aim to provide significant benefit to those affected by the condition. Orphan status provides companies with development and market exclusivity incentives for designated compounds and medicines.

In addition to ongoing Phase II/III trials in CLL, MCL and WM, acalabrutinib is currently being tested in Phase I/II trials in monotherapy as well as in combination with immunotherapy or chemotherapies in a range of other blood cancers and solid tumours.

NOTES TO EDITORS

i Chronic Lymphocytic Leukemia. Leukemia & Lymphoma Society Website. View Source Accessed February 19, 2016.

ii What are the key statistics for chronic lymphocytic leukemia? American Cancer Society Website. View Source . Accessed February 19, 2015.

iii Veliz M, Pinilla-Ibarz J. Treatment of relapsed or refractory chronic lymphocytic leukemia. Cancer Control. 2012; 19(1):37-53.

iv Chronic lymphocytic leukemia/Small lymphocytic lymphoma, National Cancer Institute Website. View Source Accessed February 19, 2016.

v Campo E and Rule S. Mantle cell lymphoma: evolving management strategies. Blood. 2015 Jan 1;125(1):48-55.

vi Mantle Cell Lymphoma, Lymphoma.org Website. View Source Accessed February 19, 2016.

vi Lymphoplasmacytic lymphoma. National Cancer Institute. Surveillance, Epidemiology, and End Results program. View Source Accessed February 19, 2016.

vii Dimopoulos MA, Kastritis E, Ghobrial IM. Waldenström’s macroglobulinemia: a clinical perspective in the era of novel therapeutics. Ann Oncol. 2016 Feb;27(2):233-40.

viii Oza and Rajkumar. Waldenstrom macroglobulinemia: prognosis and management. Blood Cancer Journal (2015) 5, e394; doi:10.1038/bcj.2015.28

ix European Medicines Agency web site. "Orphan Designation." View Source Accessed February 17, 2016.

About Acalabrutinib

Acalabrutinib is a highly selective, irreversible, second generation BTK inhibitor, with approximately 1,000 patients treated to date in clinical studies across the entire development programme. More than 600 patients have been treated with acalabrutinib monotherapy. Phase I/II data showing a favourable safety profile and efficacy in relapsed/refractory chronic lymphocytic leukaemia patients was presented at the American Society of Haematology Annual Meeting & Exposition in December 2015, with simultaneous publication in the New England Journal of Medicine.

Potentially registrational studies in haematological malignancies are ongoing. In addition, a head-to-head study versus ibrutinib in high risk chronic lymphocytic leukaemia patients is currently ongoing.

Acalabrutinib is also currently being tested in multiple Phase I/II studies in solid tumours, as monotherapy or in combination with immune checkpoint inhibitors or other standard of care regimens.