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AstraZeneca to update on leading lung cancer portfolio at WCLC 2015

On September 4, 2015 AstraZeneca reported that data will be reported from across their industry-leading lung cancer portfolio at the World Conference on Lung Cancer (WCLC) 2015, beginning this weekend in Denver, Colorado (Press release, AstraZeneca, SEP 3, 2015, View Source;astrazeneca-to-update-lung-cancer-portfolio-at-wclc [SID:1234507394]). Presentations will feature 25 abstracts (including 9 oral and 4 late breaker presentations) on the company’s lung cancer pipeline, designed to address the unmet needs of patients with different forms of lung cancer.

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AZD92911: Targeting resistance mechanisms in lung cancer

AZD9291 will be the focus of six oral presentations on its clinical activity in both first-line and previously-treated patients with epidermal growth factor receptor mutation (EGFRm) T790M advanced non-small cell lung cancer (NSCLC). The data are consistent with previously reported efficacy and safety results of AZD9291 in these treatment settings.

Antoine Yver, Head of Oncology, Global Medicines Development at AstraZeneca said: "The data presented at WCLC illustrate the breadth of our lung cancer research across multiple disease settings and lines of therapy, as we aim to develop a comprehensive portfolio of effective and durable treatments for patients. AZD9291 is moving through clinical development with unprecedented speed, and was recently granted US Priority Review designation in recognition of its potential to target the mutation that drives resistance to current treatments for EGFR mutation positive advanced non-small cell lung cancer in the majority of patients."

In addition to AZD9291, AstraZeneca will also present results from the IRESSA (gefitinib) Clinical Access Programme (ICAP), which provides data on the long-term safety and tolerability of the EGFR tyrosine kinase inhibitor in 188 US cancer patients outside the clinical trial setting. IRESSA was approved by the US Food and Drug Administration (FDA) as a first-line treatment for EGFRm metastatic NSCLC in July 2015, and is already available in 91 countries worldwide.

Immuno-oncology (IO): Update on key clinical trials

Trial designs for the ongoing IO late-stage studies that will be presented at WCLC include:

ATLANTIC (NCT02087423): A Phase II trial of durvalumab (PD-L1 mAb) as third-line treatment in patients with PD-L1 positive, locally advanced or metastatic NSCLC
ARCTIC (NCT 02352948): A Phase III trial of durvalumab monotherapy and in combination with tremelimumab (CTLA-4 mAb) versus standard of care in third-line metastatic NSCLC
PACIFIC (NCT02125461): A Phase III placebo-controlled trial of durvalumab compared to placebo in patients with locally advanced, unresectable, NSCLC following completion of treatment with chemoradiotherapy and no evidence of tumour progression.
Robert Iannone, Head of Immuno-Oncology, Global Medicines Development, at AstraZeneca said: "WCLC provides another opportunity for us to update the medical community on our extensive immuno-oncology development programme in lung cancer. We have made tremendous progress in developing immuno-oncology-based combination approaches, with nine pivotal studies planned or underway in NSCLC alone, which will provide us with a steady stream of research milestones in the coming months."

The FDA has granted Fast Track designation to tremelimumab for the treatment of mesothelioma, an aggressive, rare form of cancer that affects the lining of the lungs and abdomen. Durvalumab was also granted Fast Track designation for patients with advanced NSCLC, who have received at least two prior systemic-treatment regimens, who do not have EGFR mutations or anaplastic lymphoma kinase (ALK) alterations, and have tumours that are determined to be PD-L1 positive.

AstraZeneca Pivotal Studies in Lung Cancer

Data presented at WCLC are part of AstraZeneca’s rapidly advancing lung cancer programme, which includes the following pivotal clinical trials and upcoming milestones.

CytRx Announces the Presentation of its Phase 2b Clinical Trial Design in Small Cell Lung Cancer at the World Conference on Lung Cancer in Denver, Colorado

On Septenber 3, 2015 CytRx Corporation (Nasdaq: CYTR), a biopharmaceutical research and development company specializing in oncology, reported that the Phase 2b clinical trial design of its clinical trial in small-cell lung cancer (SCLC) will be presented in the P3.07 Poster Session on SCLC at the 16th World Conference on Lung Cancer in Denver, Colorado, September 6 – 9, 2015 (Press release, CytRx, SEP 3, 2015, View Source;p=RssLanding&cat=news&id=2085122 [SID:1234507391]). Entitled "Phase 2 Study of Aldoxorubicin versus Topotecan for Relapsed/Refractory Small Cell Lung Cancer" (Poster # 1736), the poster will be available starting at 9:30 AM MDT, on September 9, 2015. Additionally, aldoxorubicin will be discussed in the Novel SCLC Therapies Mini Symposium (MS 16) on September, 8, 2015.

"We are pleased to present the aldoxorubicin Phase 2b clinical trial design in SCLC at the World Conference on Lung Cancer," said Steven A. Kriegsman, Chairman and Chief Executive Officer. "We believe this will raise awareness of aldoxorubicin’s potential to treat patients with relapsed or refractory SCLC, a devastating disease with a large unmet need. In prior Phase 1 trials, we have seen encouraging evidence of SCLC patients with tumor shrinkage and prolonged stable disease. Our previous data in relapsed or refractory solid tumor patients indicates that the dose of aldoxorubicin being administered to these patients is well tolerated and without any treatment-limiting side effects. Up to 21 cycles (4.8 grams/m2) have been given to one patient with small cell lung cancer with minimal side effects and good anti-tumor activity."

The Phase 2b trial is currently enrolling 132 patients at 37 sites in the USA, Hungary and Spain. Patients with metastatic small cell lung cancer who have either relapsed or were refractory to prior chemotherapy will receive either aldoxorubicin or topotecan in a 1:1 randomization. The primary endpoint for the trial is progression-free survival. Overall survival and safety are secondary endpoints.

About Small Cell Lung Cancer

An estimated 1.6 million new cases of lung cancer are diagnosed worldwide each year. In the Western world, approximately 13-15% of cases are SCLC, a deadly form of lung cancer associated with tobacco use. The five year survival rate is less than 7%, in part because an estimated 70% of patients have extensive disease at diagnosis. According to the National Cancer Institute, more than 30,000 new cases were diagnosed in the USA in 2014. The estimated 2014 SCLC incidences for Europe and Asia are over 58,000 and 136,000, respectively.

About Aldoxorubicin

The widely used chemotherapeutic agent doxorubicin is delivered systemically and is highly toxic, which limits its dose to a level below its maximum therapeutic benefit. Doxorubicin also is associated with many side effects, especially the potential for damage to heart muscle at cumulative doses greater than 450 mg/m2. Aldoxorubicin combines doxorubicin with a novel single-molecule linker that binds directly and specifically to circulating albumin, the most plentiful protein in the bloodstream. Protein-hungry tumors concentrate albumin, thus increasing the delivery of the linker molecule with the attached doxorubicin to tumor sites. In the acidic environment of the tumor, but not the neutral environment of healthy tissues, doxorubicin is released. This allows for greater doses (3 ½ to 4 times) of doxorubicin to be administered while reducing its toxic side effects. In studies thus far there has been no evidence of clinically significant effects of aldoxorubicin on heart muscle, even at cumulative doses of drug well in excess of 2,000 mg/m2.

MD Anderson Cancer Center and Cellectis Announce a Broad Preclinical and Clinical Strategic Alliance in Cancer Immunotherapy

On September 3rd 2015 Cellectis (Alternext: ALCLS – Nasdaq: CLLS), the gene editing company employing proprietary technologies to develop best-in-class CAR Tcell products in adoptive immunotherapy for cancer, and The University of Texas MD Anderson Cancer Center reported that they have entered into a research and development alliance aimed at bringing novel cellular immunotherapies to patients suffering from different types of liquid tumors (Press release, Cellectis, SEP 3, 2015, View Source [SID:1234507393]).

The alliance is aimed at developing novel cancer immunotherapies based on Cellectis’ allogeneic chimeric antigen receptor (CAR) platform. MD Anderson Cancer Center’s leukemia and myeloma teams will work with Cellectis to bring better treatments to patients suffering from cancers with high unmet needs, particularly multiple myeloma (MM), acute lymphocytic leukemia (ALL), T-cell acute lymphocytic leukemia (ALL) and blastic plasmacytoid dendritic cell neoplasm (BPDCN).

The alliance will build on MD Anderson’s outstanding translational and state-of-the-art preclinical and clinical teams in leukemia and myeloma, coupled with Cellectis’ first-in-class allogeneic CAR T-cell therapy approach and manufacturing capabilities, to pursue the development of Cellectis’ candidate products UCARTCS1, UCART22, UCART38 in T-cell ALL and UCART123 in a rare non curable disease BPDCN. Cellectis has built an allogeneic CAR T-cell approach based on proprietary gene editing technologies, aimed at developing off-the-shelf cellular therapies for cancer treatment.

At MD Anderson, the alliance will be brought forward under the direction of Hagop Kantarjian, MD, Chair, Department of Leukemia, and Robert Orlowski, MD, PhD, Department Ad Interim Chair, Department of Lymphoma/Myeloma. MD Anderson’s Leukemia Department is known for its clinical trials and patient treatment using chemotherapies, tyrosine kinase inhibitors and monoclonal antibodies.

"We are extremely proud to have our research teams partnering with MD Anderson as we aim to address treatments for different types of liquid tumors," said Mathieu Simon, MD, Executive Vice President and Chief Operating Officer at Cellectis. "This alliance could potentially drive to 5 clinical developments within a time horizon of 3 years. Together, we are confident that we will quickly bring new therapeutic solutions to patients."

"Our efforts are always focused on providing more effective care for our patients," said Kantarjian. "Alliances such as this one are one more way that we can explore how to bring the latest therapies to the patients who need them."

"Significant unmet medical need exists in many types of liquid tumors. Cellectis is committed to changing patient expectations as we’re building a portfolio of candidate products in immune-oncology through our own research and key collaborations such as with MD Anderson," said André Choulika, Ph.D., Chief Executive Officer and Chairman of Cellectis.

"We’re highly encouraged by the potential of our product candidate pipeline to deliver innovative, best-in-class treatment options to patients."

"Immunotherapy is increasingly a significant element in cancer treatment," said Orlowski. "It is my hope that patients with multiple myeloma and other cancers will benefit through this alliance."

Sandoz launches ZarxioTM (filgrastim-sndz), the first biosimilar in the United States

On September 3, 2015 Sandoz, a Novartis company, reported that Zarxio(TM) (filgrastim-sndz) is now available in the United States. Zarxio is the first biosimilar approved by the US Food and Drug Administration (FDA) and the first to launch in the US (Press release, Novartis, SEP 3, 2015, View Source [SID:1234507390]).

"As the pioneer and global leader in biosimilars, Sandoz has maintained a commitment to bringing high-quality biosimilar medicines to patients and healthcare professionals around the world," said Richard Francis, Global Head, Sandoz. "With the launch of Zarxio, we look forward to increasing patient, prescriber and payor access to filgrastim in the US by offering a high-quality, more affordable version of this important oncology medicine."

"While biologics have had a significant impact on how diseases are treated, their cost and co-pays are difficult for many patients and the healthcare budget in general. Biosimilars can help to fill an unmet need by providing expanded options, greater affordability and increased patient access to life-saving therapies," said Dr. Ralph Boccia, Medical Director of the Center for Cancer and Blood Disorders, and Chief Medical Officer for the International Oncology Network (ION).

Sandoz understands the importance of providing comprehensive patient support services in the oncology setting. With the launch of Zarxio, Sandoz is also proud to offer Sandoz One SourceTM a patient services center, providing support that connects the patient to the information and resources they need.

The launch follows the FDA approval of Zarxio on March 6, 2015. The approval, via the new biosimilars pathway established under the Biologics Price Competition and Innovation Act, was based on a comprehensive package of analytical, nonclinical, and clinical data, which confirmed that Zarxio is highly similar with no clinically meaningful differences to the US-licensed reference product. The successful Sandoz pivotal head-to-head PIONEER study was the final piece of data contributing to the totality of evidence used by FDA to approve Zarxio as biosimilar to the reference product. Importantly, the data demonstrating high similarity was sufficient to allow extrapolation of use of Zarxio to five indications of the reference product.

Sandoz has an unwavering commitment to increasing patient access to high-quality, life-enhancing biosimilars. Sandoz is the global market leader and currently markets three biosimilars outside the US. Sandoz has a leading pipeline with several biosimilars across the various stages of development, including five programs in Phase III clinical trials/filing preparation.

For more information on Zarxio, please visit www.zarxio.com (link is external).

INDICATIONS

Patients with Cancer Receiving Myelosuppressive Chemotherapy: to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a significant incidence of severe neutropenia with fever.

Patients with Acute Myeloid Leukemia Receiving Induction or Consolidation Chemotherapy: to reduce the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of patients with acute myeloid leukemia (AML).

Patients with Cancer Undergoing Bone Marrow Transplantation: to reduce the duration of neutropenia and neutropenia-related clinical sequelae, e.g., febrile neutropenia, in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation.

Patients Undergoing Autologous Peripheral Blood Progenitor Cell Collection and Therapy: for the mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis.

Patients with Severe Chronic Neutropenia: for chronic administration to reduce the incidence and duration of sequelae of neutropenia (e.g, fever, infections, oropharyngeal ulcers) in symptomatic patients with congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia.
IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

ZARXIO is contraindicated in patients with a history of serious allergic reactions to human granulocyte colony-stimulating factors such as filgrastim or pegfilgrastim.

WARNINGS AND PRECAUTIONS

Splenic rupture, including fatal cases, has been reported following the administration of filgrastim products. Patients who report left upper abdominal or shoulder pain should be evaluated.

Acute respiratory distress syndrome (ARDS) has been reported in patients receiving filgrastim products. Patients who develop fever and lung infiltrates or respiratory distress should be evaluated. Discontinue ZARXIO in patients with ARDS.

Serious allergic reactions, including anaphylaxis, have been reported in patients receiving filgrastim products. The majority of reported events occurred upon initial exposure. Provide symptomatic treatment for allergic reactions. Allergic reactions, including anaphylaxis, in patients receiving filgrastim products can recur within days after the discontinuation of initial anti-allergic treatment. Permanently discontinue ZARXIO in patients with serious allergic reactions.

Sickle cell crisis, in some cases fatal, has been reported with the use of filgrastim products in patients with sickle cell trait or sickle cell disease.

Glomerulonephritis has occurred in patients receiving filgrastim products. The diagnoses were based upon azotemia,hematuria (microscopic and macroscopic), proteinuria, and renal biopsy. Generally, events of glomerulonephritis resolved after dose reduction or discontinuation of filgrastim. If glomerulonephritis is suspected, evaluate for cause. If causality is likely, consider dose-reduction or interruption of ZARXIO.

Alveolar hemorrhage manifesting as pulmonary infiltrates and hemoptysis requiring hospitalization have been reported in healthy donors treated with filgrastim undergoing peripheral blood progenitor cell (PBPC) collection mobilization. Hemoptysis resolved with discontinuation of filgrastim. The use of ZARXIO for PBPC mobilization in healthy donors is not an approved indication.
Capillary leak syndrome (CLS) has been reported after G-CSF administration, including filgrastim products, and is characterized by hypotension, hypoalbuminemia, edema and hemoconcentration. Episodes vary in frequency, severity and may be life-threatening if treatment is delayed. Patients who develop symptoms of capillary leak syndrome should be closely monitored and receive appropriate treatment.

Confirm the diagnosis of severe chronic neutropenia (SCN) before initiating ZARXIO therapy. Myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) have been reported to occur in the natural history of congenital neutropenia without cytokine therapy. Cytogenetic abnormalities, transformation to MDS, and AML have also been observed in patients treated with filgrastim for SCN. Abnormal cytogenetics and MDS have been associated with the eventual development of myeloid leukemia. The effect of filgrastim products on the development of abnormal cytogenetics and the effect of continued filgrastim administration in patients with abnormal cytogenetics or MDS are unknown. If a patient with SCN develops abnormal cytogenetics or myelodysplasia, the risks and benefits of continuing ZARXIO should be carefully considered.

Thrombocytopenia has been reported in patients receiving filgrastim products. Monitor platelet counts.

Leukocytosis:
Patients with Cancer Receiving Myelosuppressive Chemotherapy: White blood cell counts of 100,000/mm3 or greater were observed in approximately 2% of patients receiving filgrastim at dosages above 5 mcg/kg/day. In patients with cancer receiving ZARXIO as an adjunct to myelosuppressive chemotherapy, to avoid the potential risks of excessive leukocytosis, it is recommended that ZARXIO therapy be discontinued if the ANC surpasses 10,000/mm3 after the chemotherapy-induced ANC nadir has occurred. Monitor CBCs at least twice weekly during therapy.

Peripheral Blood Progenitor Cell (PBPC) Collection and Therapy: During the period of administration of ZARXIO for PBPC mobilization in patients with cancer, discontinue ZARXIO if the leukocyte count rises to >100,000/mm3.

Cutaneous vasculitis has been reported in patients treated with filgrastim products. In most cases, the severity of cutaneous vasculitis was moderate or severe. Most of the reports involved patients with SCN receiving long-term filgrastim therapy. Hold ZARXIO therapy in patients with cutaneous vasculitis. ZARXIO may be started at a reduced dose when the symptoms resolve and the ANC has decreased.

The possibility that filgrastim acts as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which filgrastim is not approved, cannot be excluded. The safety of filgrastim products in chronic myeloid leukemia (CML) and myelodysplasia has not been established. When ZARXIO is used to mobilize PBPC, tumor cells may be released from the marrow and subsequently collected in the leukapheresis product. Available data is limited and inconclusive.

The safety and efficacy of filgrastim products given simultaneously with cytotoxic chemotherapy have not been established. Do not use ZARXIO in the period 24 hours before through 24 hours after the administration of cytotoxic chemotherapy. The safety and efficacy of filgrastim products have not been evaluated in patients receiving concurrent radiation therapy. Avoid the simultaneous use of ZARXIO with chemotherapy and radiation therapy.

Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone-imaging changes on nuclear imaging.

ADVERSE REACTIONS

Most common adverse reactions in patients:

With nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs (>= 5% difference in incidence compared to placebo) are thrombocytopenia, nausea, pyrexia, chest pain, pain, fatigue, back pain, arthralgia, bone pain, pain in extremity, dizziness, cough, dyspnea, rash, blood lactate dehydrogenase increased and blood alkaline phosphatase increased

With AML (>= 2% difference in incidence) are epistaxis, back pain, pain in extremity, erythema, and rash maculo-papular
With nonmyeloid malignancies undergoing myeloablative chemotherapy followed by BMT (>= 5% difference in incidence) are rash and hypersensitivity

Undergoing peripheral blood progenitor cell mobilization and collection (>= 5% incidence) are bone pain, pyrexia, blood alkaline phosphatase increased and headache

With severe chronic neutropenia (SCN) (>= 5% difference in incidence) are arthralgia, bone pain, back pain, muscle spasms, musculoskeletal pain, pain in extremity, splenomegaly, anemia, upper respiratory tract infection, urinary tract infection, epistaxis, chest pain, diarrhea, hypoesthesia, and alopecia

10-K – Annual report [Section 13 and 15(d), not S-K Item 405]

(Filing, 10-K, MEI Pharma, SEP 2, 2015, View Source [SID:1234507383])