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Phase 1 Data for Flotetuzumab, MacroGenics’ CD123 x CD3 DARTÂ® Molecule, Accepted for Oral Presentation at ESMO Congress 2017

On July 17, 2017 MacroGenics, Inc. (NASDAQ: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, as well as autoimmune disorders and infectious diseases, reported that data from the ongoing Phase 1 clinical study of flotetuzumab has been accepted for an oral presentation at the European Society for Medical Oncology Annual Congress, ESMO (Free ESMO Whitepaper) 2017, taking place in Madrid, Spain from September 8-12, 2017 (Press release, MacroGenics, JUL 17, 2017, View Source [SID1234519806]). The Phase 1 study (NCT02152956) is evaluating the safety and efficacy of flotetuzumab, a bispecific DART molecule that recognizes both CD123 and CD3, for the investigational treatment of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).

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MacroGenics will present the following oral presentation:
Title: Interim Results from a Phase 1 First-in-Human study of flotetuzumab, a CD123 x CD3 bispecific DART molecule, in AML/MDS
Date: September 10, 2017
Time: 11:00 CEST
Full session details and data presentation listings for ESMO (Free ESMO Whitepaper) 2017 Congress can be found at View Source

About Flotetuzumab
Flotetuzumab (also known as MGD006 and S80880) is a clinical-stage molecule that recognizes both CD123 and CD3. CD123, the Interleukin-3 receptor alpha chain, has been reported to be over-expressed on cancer cells in a wide range of hematological malignancies including AML and MDS. The primary mechanism of action of flotetuzumab is believed to be its ability to redirect T lymphocytes to kill CD123-expressing cells. To achieve this, the DART molecule combines a portion of an antibody recognizing CD3, an activating molecule expressed by T cells, with an arm that recognizes CD123 on the target cancer cells.

Flotetuzumab is currently being evaluated in the U.S. and Europe in a Phase 1 dose-escalation study designed to assess the safety and tolerability of the molecule in patients with relapsed/refractory AML or MDS. MacroGenics retains full development and commercialization rights to flotetuzumab in the U.S., Canada, Mexico, Japan, South Korea and India. Servier participates in the development and has rights to flotetuzumab in all other countries. The U.S. Food and Drug Administration has granted orphan drug designation to flotetuzumab for the investigational treatment of AML.

Polaris Group Announces Treatment of First Patient in Phase 1 Study of ADI‑PEG 20 Plus Pembrolizumab in Advanced Solid Tumors

On July 14, 2017 Polaris Group reported that the first patient has been dosed in its phase 1 trial of ADI‑PEG 20 in combination with pembrolizumab for the treatment of advanced solid tumors (Press release, Polaris Pharmaceuticals, JUL 14, 2017, View Source [SID1234526284]). In addition to a global phase 2/3 trial in malignant plural mesothelioma featuring ADI‑PEG 20 in combination with pemetrexed and cisplatin (PemCis), Polaris Group is currently conducting multiple phase 1 clinical trials, including ADI‑PEG 20 in combination with PemCis in non-small cell lung carcinoma, glioblastoma, and uveal melanoma, in combination with low-dose cytarabine in older patients with acute myeloid leukemia and in combination with FOLFOX in hepatocellular carcinoma, gastric cancer, and colorectal cancer.

"In addition to its enzymatic activity to breakdown arginine, ADI‑PEG 20 has also shown immune regulating activities in pre-clinical studies. We hope the combination will further enhance pembrolizumab’s efficacy while conferring additional anti-tumor activity from ADI‑PEG 20", said John Bomalaski, M.D., Executive Vice President, Medical Affairs at Polaris Pharmaceuticals, Inc.

About ADI‑PEG 20

ADI‑PEG 20 is a biologic being developed by Polaris Group to treat cancers carrying a major metabolic defect that renders them unable to internally synthesize arginine. Because arginine is essential for protein synthesis and survival of cells, these cancer cells become dependent upon the external supply of arginine to survive and grow. ADI‑PEG 20 is designed to deplete the external supply of arginine, causing arginine-dependent cancer cells to die while leaving the patient’s normal cells unharmed. Multiple cancers have been reported to have a high degree of arginine-dependency and can potentially be treated with ADI‑PEG 20.

Amgen Submits Regulatory Applications In US And Europe To Include Overall Survival Data In KYPROLIS® (Carfilzomib) Label

On July 14, 2017 Amgen (NASDAQ:AMGN) reported the submission of a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) and a variation to the marketing application to the European Medicines Agency (EMA) to include overall survival (OS) data from the Phase 3 head-to-head ENDEAVOR trial in the product information for KYPROLIS (carfilzomib) (Press release, Amgen, JUL 14, 2017, View Source [SID1234519801]).

Data submitted to regulatory authorities showed that KYPROLIS, administered at the 56 mg/m2 dose as a 30-minute infusion twice weekly with dexamethasone (Kd56), reduced the risk of death by 21 percent over Velcade (bortezomib) and dexamethasone (Vd), resulting in a 7.6 month OS benefit (median OS 47.6 months for Kd56 versus 40.0 months for Vd, HR=0.79; p=0.01). The OS benefit was consistent regardless of prior bortezomib therapy (HR 0.75 for no prior Velcade; HR 0.84 for prior Velcade). These results were presented earlier this year at the 16th International Myeloma Workshop and the 22nd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper).

"KYPROLIS is the first-and-only multiple myeloma therapy to demonstrate superior overall survival in a head-to-head comparison with a current standard of care, extending survival by 7.6 months over Velcade," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "We submitted these important data to regulatory authorities in the U.S. and Europe because we know that KYPROLIS may offer appropriate multiple myeloma patients a better chance for a longer life at first relapse compared to Velcade when added to dexamethasone."

Since its approval in 2012, KYPROLIS has been prescribed to more than 50,000 patients worldwide. The KYPROLIS clinical program continues to focus on providing solutions for physicians and patients in treating this frequently relapsing and difficult-to-treat cancer. KYPROLIS is available for patients whose myeloma has relapsed or become resistant to another treatment and continues to be studied in a range of combinations and patient populations.

Adverse events observed in this updated analysis were consistent with those previously reported for ENDEAVOR. The most common adverse events (greater than or equal to 20 percent) in the KYPROLIS arm were anemia, diarrhea, pyrexia, dyspnea, fatigue, hypertension, cough, insomnia, upper respiratory tract infection, peripheral edema, nausea, bronchitis, asthenia, back pain, thrombocytopenia and headache.

About ENDEAVOR
The randomized ENDEAVOR (RandomizEd, OpeN Label, Phase 3 Study of Carfilzomib Plus DExamethAsone Vs Bortezomib Plus DexamethasOne in Patients With Relapsed Multiple Myeloma) trial of 929 patients evaluated Kd56 versus Vd in patients whose multiple myeloma has relapsed after at least one, but not more than three prior therapeutic regimens. The primary endpoint of the trial was progression-free survival, defined as the time from treatment initiation to disease progression or death. The primary analysis was published in The Lancet Oncology and is described in the Prescribing Information.

Patients received treatment until progression with KYPROLIS as a 30-minute infusion on days 1, 2, 8, 9, 15 and 16 of 28 day treatment cycles, along with low-dose dexamethasone (20 mg). For cycle one only, KYPROLIS was administered at 20 mg/m2 on days 1 and 2, and if tolerated was escalated to 56 mg/m2 from day 8 cycle one onwards. Patients who received bortezomib (1.3 mg/m2) with low-dose dexamethasone (20 mg) were treated with bortezomib administered subcutaneously or intravenously at the discretion of the investigator and in accordance with regional regulatory approval of bortezomib. Eighty-two percent of the patients in the control arm received bortezomib subcutaneously. This study was conducted at 235 sites worldwide. For information about this trial, please visit www.clinicaltrials.gov under trial identification number NCT01568866.

Kite Highlights Durable Complete Remissions Up to 56+ Months in Patients with Chemorefractory Aggressive Non-Hodgkin Lymphoma (NHL) after Anti-CD19 CAR T-Cell Therapy at the National Cancer Institute

On July 20, 2017 Kite Pharma, Inc. (Nasdaq:KITE), a leading cell therapy company, highlighted the recent online publication of results in Molecular Therapy from a National Cancer Institute (NCI) study of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in patients with aggressive NHL including diffuse large B-cell lymphoma (DLBCL) (Press release, Kite Pharma, JUL 13, 2017, View Source [SID1234521047]). The research, led by James N. Kochenderfer, M.D., an Investigator in the Experimental Transplantation and Immunology Branch of the NCI Center for Cancer Research, and Steven A. Rosenberg, M.D., Ph.D., Chief of the Surgery Branch at NCI’s Center for Cancer Research, was performed pursuant to a Cooperative Research and Development Agreement (CRADA) between NCI and Kite.

This work follows previously published data in the February 2015 issue of the Journal of Clinical Oncology in which nine patients with chemorefractory aggressive NHL were treated with a single dose of anti-CD19 CAR T cells with a CD28 co-stimulatory domain. Seven of the 9 patients were evaluable for response. Complete remissions (CR) were observed in 5 of the 7 evaluable patients. Four of the 5 CRs are ongoing from 38 to 56+ months after treatment. There were no chronic toxicities attributable to CAR T cells except B-cell aplasia and hypogammaglobulinemia. Importantly, 3 of 4 patients in ongoing CR had recovery of normal polyclonal B cells, showing that durable CRs can be maintained in the absence of continued activity of anti-CD19 CAR T cells.

"We are encouraged to see durable CRs ongoing for more than 3 years, which raises a possibility of cure, from a single infusion of anti-CD19 CAR T cells in patients with chemorefractory DLBCL, a population that previously had no curative treatment options. This study helps us to understand the long-term potential for this anti-CD19 CAR T cell therapy (axicabtagene ciloleucel) in the larger aggressive NHL patient population," said David Chang, M.D., Ph.D., Executive Vice President of Research and Development and Chief Medical Officer of Kite.

FDA Advisory Committee Unanimously Recommends CTL019 (tisagenlecleucel) for Approval

On July 13, 2017 Oxford BioMedica plc ("Oxford BioMedica" or "the Group") (LSE:OXB), a leading gene and cell therapy group, reported that the US Food and Drug Administration’s (FDA) Oncologic Drugs Advisory Committee voted unanimously 10 to 0 in favour of approval of Novartis investigational therapy CTL019 (tisagenlecleucel) for the treatment of relapsed and refractory (r/r) paediatric and young adult patients with B-cell acute lymphoblastic leukaemia (ALL) (Press release, Oxford BioMedica, JUL 13, 2017, View Source [SID1234519799]).

Novartis announced in March that the FDA accepted its BLA filing and granted priority review for CTL019 in paediatric and young adult patients with B-cell ALL. The BLA review is ongoing and is under FDA priority review.

Oxford BioMedica is the sole manufacturer of the lentiviral vector that encodes CTL019. As announced in October 2014, Oxford BioMedica will also receive undisclosed royalties on potential future sales of Novartis CAR-T products. Oxford BioMedica recently signed an agreement with Novartis for the commercial and clinical supply of lentiviral vectors used to generate CTL019 and other undisclosed CAR-T products, for which Oxford BioMedica could potentially receive in excess of $100m from Novartis over the next three years.

John Dawson, Chief Executive Officer of Oxford BioMedica, commented: "The positive vote by 10 to 0 provides further support for CTL019, a novel immunocellular therapy, and we are proud to be a part of this important development. We continue to work closely with Novartis in delivering the lentiviral vector that encodes CTL019, a product the company described earlier this year as having "blockbuster" potential."