On December 7, 2015 Kite Pharma, Inc. (Nasdaq:KITE) reported that it has initiated a phase 1/2 clinical study of KTE-C19 (ZUMA-4) for the treatment of pediatric and young adult patients with r/r ALL (Press release, Kite Pharma, DEC 7, 2015, View Source [SID:1234508442]). KTE-C19 is an investigational therapy in which a patient’s T cells are genetically modified to express a chimeric antigen receptor designed to target the antigen CD19, a protein expressed on the cell surface of B cell lymphomas and leukemias.

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"With the commencement of ZUMA-4, Kite has achieved its goal of initiating four company-sponsored trials this year for its lead product candidate, KTE-C19," said David Chang, M.D., Ph.D., Kite’s Executive Vice President, Research and Development, and Chief Medical Officer. "Our ZUMA trials are investigating critical needs in non-Hodgkin lymphoma (NHL) and ALL in patients with advanced, relapsed or refractory disease who have few or no other treatment options."

"We are enthusiastic about the possibility that KTE-C19 could safely put children and young adults who have persistent ALL despite multiple prior standard therapies into complete remissions," said internationally recognized leukemia expert Leonard S. Sender, M.D., Medical Director and Division Chief, and ZUMA-4 trial investigator, at Children’s Hospital of Orange Country. "Kite has done an outstanding job advancing immunotherapy for testing in multiple multi-center trials, and we are thrilled to offer this trial to our young patients and their families."

ZUMA-4 will proceed as a single-arm, open-label, multi-center study in patients with ALL whose disease is refractory to or has relapsed following standard chemotherapy or hematopoietic stem cell transplantation. The phase 1 portion of ZUMA-4 will assess the safety of KTE-C19, and the phase 2 portion will assess efficacy and safety. The study will target to enroll a total of 75 patients. Additional details about this study will be available on ClinicalTrials.gov.

On December 7, 2015 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported follow-up results from the pivotal phase III GADOLIN study in people with indolent non-Hodgkin lymphoma (iNHL) who relapsed during or within six months after treatment with a MabThera/Rituxan (rituximab)-based regimen (Press release, Hoffmann-La Roche , DEC 7, 2015, View Source [SID:1234508440]). In a subgroup analysis of people with follicular lymphoma, the most common type of iNHL, treatment with Gazyva/Gazyvaro (obinutuzumab) plus bendamustine provided significantly greater depth of remission at end of induction compared to bendamustine alone, as measured by minimal residual disease (MRD)-negativity (82% vs 43%, respectively; p<0.0001)1. MRD assessment was an exploratory analysis.

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"Building on the significant progression-free survival benefit previously reported in the GADOLIN study, these follow-up data show that Gazyva/Gazyvaro-based treatment achieves significant rates of deep remission, known as minimal residual disease negativity, at the end of induction treatment," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "This achievement is particularly impressive in this difficult-to-treat patient population with follicular lymphoma, for whom treatment options are limited."

An additional analysis of the overall study population in the GADOLIN trial showed that a greater proportion of patients in the Gazyva/Gazyvaro arm reported a meaningful improvement in health-related quality of life (HRQoL) compared to those treated with bendamustine alone. HRQoL was a secondary endpoint in the study. This finding suggests that increased progression-free survival (PFS) does not appear to come at the expense of an increase in treatment-related toxicity that adversely impacts a patient’s quality of life.

Data from the GADOLIN MRD subgroup analysis will be presented in a poster session today, Monday December 7 by Dr. Kirsten Mundt, Senior Scientist, Roche at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper), in Orlando, Florida. Data from the GADOLIN HRQoL analysis was also presented on Saturday, December 5, during a poster session by Dr. Peter Trask, Principal Scientist, Genentech and Professor Bruce Cheson from the Georgetown University Hospital, Washington DC, USA.

The FDA has accepted for priority review a supplemental Biologics License Application (sBLA) for Gazyva/Gazyvaro in the treatment of people with follicular lymphoma who relapsed after or are refractory to a MabThera/Rituxan-containing regimen. Marketing applications have also been submitted to other global regulatory authorities, including the EMA, for approval consideration in the treatment of people with follicular lymphoma who did not respond or who progressed during or up to six months after treatment with MabThera/Rituxan or a MabThera/Rituxan-containing regimen.

About the GADOLIN study
GADOLIN is a phase III open-label, multicentre, randomised two-arm study evaluating Gazyva/Gazyvaro plus bendamustine followed by Gazyva/Gazyvaro alone for up to two years, compared to bendamustine alone. GADOLIN included 413 patients with iNHL whose disease progressed during or within six months of prior MabThera/Rituxan-based therapy. The primary endpoint of the study is progression-free survival (PFS) as assessed by an independent review committee (IRC), with secondary endpoints including PFS as assessed by investigator review, response rate (RR), best response and overall survival (OS). GADOLIN data presented at the annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in June this year showed the median PFS (mPFS) was not reached in the Gazyva/Gazyvaro-based treatment group versus 14.9 months with bendamustine alone (HR=0.55, p=0.0001) as assessed by IRC. The median PFS with Gazyva/Gazyvaro-based treatment was more than double that with bendamustine alone (29.2 months versus 14.0 months (HR=0.52, p<0.0001) as assessed by investigator review. No unexpected safety signals were identified in the Gazyva/Gazyvaro-based treatment arm. Grade 3-4 adverse events that occurred in at least two percent of patients in the Gazyva/Gazyvaro-treated group or bendamustine alone group included low white blood cell count (33% versus 26.3%), low blood platelet count (10.8% versus 16.2%), infusion-related reactions (10.8% versus 5.6%), low red blood cell count (7.7% versus 10.1%), low white blood cell count with fever (4.6% versus 3.5%), nausea (1% versus 3%), fatigue (1.5% versus 2.5%), diarrhoea (1% versus 2.5%), vomiting (2.1% versus 1%), respectively.

The MRD data from the subgroup analysis of people with follicular lymphoma will be presented at a poster presentation today, Monday 7 December, from 6:00-8:00 PM ET [Abstract #3978].

About Gazyva/Gazyvaro (obinutuzumab)
Gazyva/Gazyvaro is an engineered monoclonal antibody designed to attach to CD20, a protein found only on B-cells. Gazyva/Gazyvaro is designed to attack and destroy targeted B-cells both directly and together with the body’s immune system. Gazyva/Gazyvaro is currently approved in more than 60 countries in combination with chlorambucil, for people with previously untreated chronic lymphocytic leukaemia. The approval was based on the CLL11 study, showing significant improvements with Gazyva/Gazyvaro plus chlorambucil across multiple clinical endpoints, including PFS, overall response rate (ORR), complete response rate (CR), and minimal residual disease (MRD) when compared head-to-head with MabThera/Rituxan plus chlorambucil. Gazyva is marketed as Gazyvaro in the EU and Switzerland.

Gazyva/Gazyvaro is being studied in a large clinical programme, including the Phase III GOYA and GALLIUM studies. GOYA is comparing Gazyva/Gazyvaro head-to-head with MabThera/Rituxan plus CHOP chemotherapy in first line diffuse large B-cell lymphoma (DLBCL) and GALLIUM is comparing Gazyva/Gazyvaro plus chemotherapy followed by Gazyva/Gazyvaro maintenance head-to-head with MabThera/Rituxan plus chemotherapy followed by MabThera/Rituxan maintenance in first line indolent non-Hodgkin Lymphoma (iNHL). Additional combination studies investigating Gazyva/Gazyvaro with other approved or investigational medicines, including cancer immunotherapies and small molecule inhibitors, are planned or underway across a range of blood cancers.

About non-Hodgkin lymphoma
There are two main types of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma (NHL). NHL represents approximately 85 percent of all lymphomas diagnosed2. Approximately 200,000 people die each year from NHL worldwide and approximately one person is newly diagnosed every 90 seconds2. There are more than 60 different types of NHL that fall under two subsets, aggressive and indolent (slow growing). The most common type of indolent NHL is follicular lymphoma (FL), found in about 25 percent of all NHL patients3. Most cases of NHL start in B-lymphocytes, cells that are part of the body’s immune system and help to defend the body against infections. B-cell lymphoma develops when these cells become cancerous and begin to multiply and collect in the lymphatic system such as in lymph nodes, lymphatic tissues or the spleen.

On December 7, 2015 Nemucore Medical Innovations, Inc., a privately held, clinical-stage biopharmaceutical company dedicated to the development of therapies targeting multi-drug resistant cancers with a special emphasis on highly lethal women’s cancers, reported the completion of an option agreement with Cancer Research Technology Ltd (CRT), the commercial arm of Cancer Research UK, for the exclusive license of worldwide commercial rights to GSK1070916 (now designated NMI-900 by Nemucore), a potent Aurora B/C kinase inhibitor targeting a broad range of cancers (Press release, Cancer Research Technology, DEC 7, 2015, View Source [SID1234523201]).

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"We are thrilled to be able to build on the excellent foundational clinical research conducted by Cancer Research UK, and continue the development of this innovative and very promising anticancer therapeutic," said Timothy P. Coleman, Ph.D., Chairman, Chief Executive Officer and President of Nemucore. "Based on its unique properties and pharmaceutical profile, we believe NMI-900 has best-in-class potential as a breakout therapy for treating women’s and other cancers associated with high mortality rates that have already been demonstrated to be intractable to conventional therapeutics."

NMI-900 is a potent ATP-competitive inhibitor of Aurora B kinase that has demonstrated high affinity for Aurora B, a significantly slower dissociation rate compared to its peers, potent anti-proliferative activity in multiple cancer cell lines, and minimal effects on non-proliferating normal human cells. In 2014, Cancer Research UK’s Centre for Drug Development successfully completed a Phase 1/2a trial of NMI-900. In this trial, NMI-900 elicited response in 61% of patients with no remaining standard therapies available to them across a wide variety of advanced and/or metastatic solid tumors. NMI-900 was well tolerated, with the most prevalent adverse event presenting as predictable and treatable neutropenia. NMI-900 was developed by Cancer Research UK’s Centre for Drug Development in partnership with GSK, under the Clinical Development Partnerships (CDP) initiative. This initiative, a joint effort launched by Cancer Research UK and Cancer Research Technology Ltd, provides a simple route for companies to progress oncology agents that would not otherwise be developed, and increase the number of clinical trials being undertaken for the treatment of cancer.

Dr. Keith Blundy, CEO of Cancer Research Technology commented, "We’re very pleased that Nemucore plans to take this promising new drug candidate and develop it through more clinical trials so that it has a greater chance of reaching patients who are in urgent need of new treatment options, sooner. The drug forms part of our Clinical Development Partnerships initiative, and is one of twelve drugs on the scheme that are moving out of the lab into clinical trials – something that wouldn’t have been possible otherwise."

Nemucore expects to initiate a Phase 2b clinical trial of NMI-900 in patients with advanced, platinum-resistant ovarian cancer in mid-2016 based on the supportive preclinical and early clinical trial results. As part of their clinical development and commercial strategy, the Company is concurrently developing a companion diagnostic with the Medical Prognosis Institute to identify patients most likely to respond to NMI-900. Nemucore expects to investigate the efficacy of NMI-900 in the treatment of EGF receptor-positive non-small cell lung cancer (NSCLC), myelodysplastic syndrome (MDS) and other difficult-to-treat cancers in the future.