ENZALUTAMIDE (XTANDI) NOW APPROVED IN EUROPE FOR THE TREATMENT OF MEN WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER WHO ARE CHEMOTHERAPY-NAÏVE

On December 2, 2014 Astellas Pharma reported that the European Commission (EC) has granted a variation to amend the Marketing Authorisation for enzalutamide (trade name XTANDI) (Press release Astellas, DEC 2, 2014, View Source [SID:1234501049]). Enzalutamide is now approved for the treatment of adult men with metastatic castration-resistant prostate cancer (mCRPC) who are asymptomatic or mildly symptomatic after failure of androgen-deprivation therapy in whom chemotherapy is not yet clinically indicated.

The approval of the variation is based on results from the pivotal phase III PREVAIL study which demonstrate that enzalutamide improves outcomes for men with advanced prostate cancer who have not received chemotherapy.

Compared with placebo, enzalutamide reduced the risk of death by 29% (HR=0.71; p<0.001) and the risk of radiographic progression or death by 81% (HR=0.19; p<0.001). Men treated with enzalutamide experienced a 17-month delay in the time to initiation of chemotherapy compared to placebo (28.0 months versus 10.8 months, respectively; HR=0.35; p<0.001). Astellas expects to launch enzalutamide in the pre-chemotherapy setting in the first European countries, including the UK, from January 2015. The approval of this new indication for enzaltamide triggers $45 million in milestone payments to Medivation (NASDAQ: MDVN) under its collaboration agreement with Astellas. The impact has been accounted in Astellas’ financial forecasts for fiscal year ending March 2015.

Glutaminase Inhibitor CB-839 Synergizes with Pomalidomide in Preclinical Multiple Myeloma Models

On December 1, 2014 Calithera Biosciences presented the corporate presentation (Poster, ASH (Free ASH Whitepaper) 2014, Calithera Biosciences, DEC 1, 2014, View Source [SID1234535307]).

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iomarkers of Response to the Glutaminase Inhibitor CB-839 in Multiple Myeloma Cells

On December 1, 2014 Calithera Biosciences presented the corporte presentation (Presentation, Calithera Biosciences, DEC 1, 2014, View Source [SID1234535306]).

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A Novel Pharmacodynamic Assay to Measure Glutaminase Inhibition Following Oral Administration of CB-839 in Triple Negative Breast Cancer Biopsies

On December 1, 2014 Calithera Biosciences presented the corporate presentation (Presentation, Calithera Biosciences, DEC 1, 2014, View Source [SID1234535305]).

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Unum Therapeutics Announces Start of First Phase I Clinical Trial of Cellular Immunotherapy Targeting CD20+ Chronic Lymphocytic Leukemia and Non-Hodgkin Lymphoma

On December 1, 2014 Unum Therapeutics, a company developing a universal cellular immunotherapy to treat multiple cancers, announced today that recruitment has begun in the first clinical trial of the ATTCK20 therapy (Press release, Unum Therapeutics, DEC 1, 2014, View Source!2014dec01-unum-starts-phase-1/cyn5 [SID:1234505419]). The Phase I study will examine the feasibility, safety and potential efficacy of infusing the ATTCK20 combination therapy in patients with B-cell malignancies and persistent disease following standard therapy. The clinical program commences shortly after the company’s official launch in October 2014.

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"Despite recent advances in cancer treatments, there are still far too many individuals with B-cell malignancies who die from their disease," said Chuck Wilson, PhD, President & CEO of Unum Therapeutics. "With these unmet medical needs fueling our efforts, we are excited to see the start of clinical testing for ATTCK20. This novel therapy leverages two of the strongest immunotherapy technologies in modern medicine – engineered T-cells and monoclonal antibodies – to target cancer."

ATTCK20 Clinical Trial

Antibody-Targeted Tumor Cell Killing (ATTCK) happens when T-cells expressing an antibody-coupled T-cell receptor (ACTR) engage a tumor-targeting antibody on the surface of a cancer cell. ATTCK20 is a combination of a patient’s ACTR T-cells administered with rituximab, a monoclonal antibody targeting CD20. The first Phase I dose escalation study for ATTCK20 is taking place in Singapore at National University Hospital (NUH) and Singapore General Hospital (SGH). T-cells from patients in the study are processed at the Tissue Engineering & Cell Therapy (TECT) Laboratory at NUH. The Hematology-Oncology Research Group Trial Unit within the National University Cancer Institute, Singapore (View Source) manages and supports all aspects of the clinical trial. At present, the unit is conducting over 60 clinical trials, many of which are Phase I and II studies. The Hematopoietic Progenitor Cell Transplant Program is the only one in Asia accredited by the Foundation for the Accreditation of Cellular Therapy (FACT).

"This study is designed to translate recent laboratory findings into clinical application," said Unum’s Scientific Founder Dario Campana, MD, PhD. "The efficacy of ACTR T-cells shown in our preclinical studies, together with the demonstrated feasibility of infusing autologous T-cells, forms a compelling rationale for the clinical testing of this novel approach. We look forward to enrolling patients in the ATTCK20 study and will continue to plan for additional clinical studies to leverage our ACTR technology with tumor-targeting antibodies in other types of cancer."

ACTR AND ATTCK20

ACTR is a chimeric protein that combines components from receptors normally found on two different human immune cell types – natural killer (NK) cells and T-cells – to create a novel cancer cell killing activity. As reported earlier this year in the journal Cancer Research[1], T-cells bearing the ACTR receptor can be armed to attack a tumor by combining with a monoclonal antibody that binds antigens on the cancer cell surface. CD20 is expressed on cancer cells from many patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL). Rituximab, an antibody specific for CD20, is currently part of standard therapy for these indications. Studies carried out in Dr. Campana’s laboratory show remarkable enhancement in the activity of rituximab when it is armed with ACTR T-cells.

Unum has built a platform for cancer treatment based upon ACTR. In contrast to other approaches that are limited to a single target and treat a narrow set of tumors, Unum’s approach is not restricted by antigen and may have applications for treating many types of cancers. The ATTCK20 study will be the first clinical trial to assess clinical candidates engineered with the ACTR technology.