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TESARO Announces Validation of Marketing Authorisation Application for Oral Rolapitant by the European Medicines Agency

On March 23, 2016 TESARO, Inc. (NASDAQ:TSRO), an oncology-focused biopharmaceutical company, reported that the Marketing Authorisation Application (MAA) for oral rolapitant has been submitted to and validated by the European Medicines Agency (Press release, TESARO, MAR 23, 2016, View Source [SID:1234509849]). Rolapitant is a substance P/neurokinin-1 (NK-1) receptor antagonist that is marketed by TESARO in the United States under the brand name VARUBI.

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"TESARO is committed to advancing new therapeutic options for patients with cancer, and the oral rolapitant MAA submission represents a significant milestone for the Company," said Mary Lynne Hedley, Ph.D., President and COO of TESARO. "We believe rolapitant could become an important new treatment option for the prevention of nausea and vomiting for patients in Europe who are undergoing emetogenic chemotherapy."

The oral rolapitant MAA is supported by data from four controlled studies covering a spectrum of patients receiving emetogenic chemotherapy. One study enrolled patients receiving moderately emetogenic chemotherapy (MEC), and three studies enrolled patients receiving cisplatin-based highly emetogenic chemotherapy (HEC). The top-line results of each of the three Phase 3 studies of rolapitant were presented in detail at the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting in June 2014. Oral rolapitant was approved by the U.S. Food and Drug Administration on September 1, 2015 and is marketed by TESARO in the United States under the brand name VARUBI.

"TESARO has an exciting pipeline of oncology therapeutics, and with the filing of our MAA for oral rolapitant today and our planned niraparib MAA filing in the second half of this year, we look forward to globalizing our mission of providing transformative therapies to people bravely facing cancer," said Orlando Oliveira, Senior Vice President and General Manager of TESARO International.

About Chemotherapy-Induced Nausea and Vomiting (CINV)

Chemotherapy-induced nausea and vomiting is a debilitating, yet often preventable, side effect of chemotherapy.

More than 50% of patients undergoing highly or moderately emetogenic chemotherapy may experience delayed CINV (25 to 120 hours post chemotherapy)—even when prescribed a 5-HT3 receptor antagonist and corticosteroid.

Blocking both 5-HT3 and NK-1 receptors has been shown to offer better control of nausea and vomiting than inhibiting 5-HT3 receptors alone. Adding a single dose of VARUBI to an antiemetic regimen, including a 5-HT3 receptor antagonist and corticosteroid, further improves prevention of CINV in the delayed phase following chemotherapy.

About VARUBI (Rolapitant)

VARUBI is a substance P/neurokinin-1 (NK-1) receptor antagonist indicated in combination with other antiemetic agents in adults for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy. VARUBI is contraindicated in patients receiving thioridazine, a CYP2D6 substrate. The inhibitory effect of a single dose of VARUBI on CYP2D6 lasts at least seven days and may last longer. Avoid use of pimozide; monitor for adverse events if concomitant use with other CYP2D6 substrates with a narrow therapeutic index cannot be avoided. Please see full prescribing information, including additional important safety information, available at www.varubirx.com.

An intravenous formulation of rolapitant is also being developed. TESARO licensed exclusive rights for the development, manufacture, commercialization, and distribution of VARUBI (rolapitant) from OPKO Health, Inc.

Sunesis Pharmaceuticals Announces First Subject Dosed in Phase 1A Healthy Volunteer Study Evaluating Oral Non-Covalent BTK-inhibitor SNS-062

On March 23, 2016 Sunesis Pharmaceuticals, Inc. (Nasdaq:SNSS) reported that the first subject has been dosed in a Phase 1A, randomized, double-blind, placebo-controlled dose-ranging study to investigate the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of its oral, next-generation, non-covalently binding BTK-inhibitor, SNS-062, in healthy subjects (Press release, Sunesis, MAR 23, 2016, View Source [SID:1234509839]). The Phase 1A study is being conducted in Belgium, pursuant to a Clinical Trial Application (CTA). With a successful study outcome, SNS-062 is expected to proceed to a Phase 1B/2 study in patients with B-cell malignancies later this year.

"As a non-covalently binding kinase inhibitor with preclinical activity against Cys-481S mutated B-cell malignancies, SNS-062 is an important new drug candidate with the potential to address the emerging resistance to currently marketed and clinical-stage covalent-binding BTK inhibitors," said Daniel Swisher, Chief Executive Officer of Sunesis. "SNS-062’s distinct kinase selectivity profile also lends the potential for activity in a broader range of cancers. This is the second of Sunesis’ kinase inhibitors, after the Takeda-partnered TAK-580, to enter the clinic. Together with the ongoing review of our vosaroxin marketing authorization application in Europe, these programs provide for a milestone-rich period in the coming quarters."

"BTK inhibitors remain an area of keen interest among investigators and major industry participants, and we believe our clinical strategy will allow us to rapidly differentiate and reach proof-of-concept with SNS-062 in this important field of study," said Deborah Thomas, Ph.D., Senior Vice President, Regulatory Affairs, Quality Assurance, and Non-Clinical Development. "Through the CTA process, Sunesis is able to efficiently understand important aspects of SNS-062’s PK/PD profile in humans, identify a pharmacologically active dose and gather initial safety information, allowing us to move into a targeted patient population, including patients with relapsed chronic lymphoid leukemia with acquired mutations in Cys-481S, later this year."

The Phase 1A study will be conducted in three stages and is expected to enroll 52 subjects. In the first stage, the safety, pharmacokinetics, and pharmacodynamics of SNS-062 will be assessed over a range of doses. In the second stage, the effects of food on the pharmacokinetics of the drug will be assessed. In the last stage, a drug-drug interaction assessment will be conducted exploring the effects of CYP3A4 inhibition on the pharmacokinetics of SNS-062. The primary endpoint of the study is safety. The secondary endpoints are pharmacokinetics and pharmacodynamics.

About SNS-062

SNS-062 is a non-covalently binding inhibitor of Bruton’s tyrosine kinase (BTK). This target mediates signaling through the B-cell receptor, or BCR, which is critical for adhesion, migration, proliferation and survival of normal and malignant B-lineage lymphoid cells. BTK has been well validated as a target for treatment of B-cell malignancies, with a BTK inhibitor approved for relapsed/refractory mantle cell lymphoma, frontline and relapsed/refractory chronic lymphocytic leukemia, or CLL, CLL with 17p depletion and Waldenström’s macroglobulinemia. Because SNS-062 has a distinct binding site and favorable pharmacokinetic profile in preclinical studies, SNS-062 may provide differentiated opportunities for treatment of B-cell malignancies and other blood cancers. The rights to develop SNS-062 for oncology indications were in-licensed from Biogen in December 2013. SNS-062 is currently being evaluated in a Phase 1A Trial in healthy volunteers.

BioLineRx Announces Initiation of Phase 2 Trial for BL-8040 as Novel Stem Cell Mobilization Treatment

On March 23, 2016 BioLineRx Ltd. (NASDAQ/TASE:BLRX) reported the initiation of a Phase 2 trial for BL-8040 as a novel approach for the mobilization and collection of bone marrow stem cells from the peripheral blood circulation (Press release, BioLineRx, MAR 23, 2016, View Source [SID:1234509836]).

The Phase 2 open-label study will be conducted in collaboration with the Washington University School of Medicine, Division of Oncology and Hematology, and will enroll up to 24 donor/recipient pairs, aged 18-70. The trial is designed to evaluate the ability of BL-8040, as a single agent, to promote stem cell mobilization for allogeneic transplantation. On the donor side, the primary endpoint of the study is the ability of a single injection of BL-8040 to mobilize sufficient amounts of cells for transplantation following up to two leukapheresis collections. On the recipient side, the study aims to evaluate the functionality and engraftment following transplantation of the BL-8040 collected graft.

The study will also evaluate the safety and tolerability of BL-8040 in healthy donors, as well as graft durability, the incidence of grade 2-4 acute graft versus host disease (GvHD), and other recipient related parameters in patients who have undergone transplantation of hematopoietic cells mobilized with BL-8040.

Dr. Kinneret Savitsky, Chief Executive Officer of BioLineRx, stated, "We are pleased to be collaborating with the Washington University School of Medicine, whose bone marrow and stem cell transplantation program is one of the largest in the world, in this Phase 2 trial for our lead oncology platform. The trial will assess BL-8040 as a single agent for stem cell mobilization, for the purpose of harvesting hematopoietic stem cells for transplantation. Hematopoietic stem cells are increasingly used as part of the treatment regimen for certain types of hematological cancers, as well as for severe anemia or immune deficiency disorders. We have already completed a successful Phase 1 safety and efficacy study in healthy volunteers, supporting BL-8040 as one-day, single-dose collection regimen for rapidly mobilizing substantial amounts of stem cells. This represents a significant improvement upon the current standard of care. Since there are no approved drugs for stem cell mobilization to support allogeneic transplant, we are looking forward to the partial results expected by the end of 2016 and topline results expected by the end of 2017."

"We continue to expand and enhance the potential of our unique BL-8040 oncology platform, with multiple clinical studies in additional indications, including as a potential combination treatment with immune checkpoint inhibitors. We are also eagerly awaiting the top-line results from BL-8040’s Phase 2 trial for the treatment of relapsed and refractory AML patients, which we expect to report by the end of this month," added Dr. Savitsky.

About BL-8040

BL-8040 is a clinical-stage drug candidate for the treatment of acute myeloid leukemia, as well as other hematological indications. It is a short peptide that functions as a high-affinity antagonist for CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis (growth of new blood vessels in the tumor), metastasis (spread of the disease to other organs or organ parts) and cell survival. CXCR4 is over-expressed in more than 70% of human cancers and its expression often correlates with disease severity. BL-8040 is currently in the midst of a Phase 2 study for relapsed/refractory acute myeloid leukemia (AML) and has recently initiated a Phase 2b study as an AML consolidation treatment and a Phase 1/2 study in hMDS and AA,. In addition, in a Phase 1/2, open-label, dose escalation, safety and efficacy clinical trial in 18 multiple myeloma patients, BL-8040, when combined with G-CSF, demonstrated an excellent safety profile at all doses tested and was highly effective in the mobilization of hematopoietic stem cells and white blood cells from the bone marrow to the peripheral blood. Additionally, in a Phase 1 stem-cell mobilization study in healthy volunteers, BL-8040 as a single agent was safe and well tolerated at all doses tested and resulted in efficient stem-cell mobilization and collection in all study participants. Importantly, the results of this study support the use of BL-8040 as one-day, single-dose collection regimen, which is a significant improvement upon the current standard of care.

BL-8040 effectively mobilizes cancer cells from the bone marrow and may therefore sensitize these cells to chemo- and bio-based anti-cancer therapy. Importantly, BL-8040 has also demonstrated a direct anti-cancer effect by inducing apoptosis. Pre-clinical studies show that BL-8040 inhibits the growth of various tumor types including multiple myeloma, non-Hodgkin’s lymphoma, leukemia, non-small cell lung carcinoma, neuroblastoma and melanoma. BL-8040 also significantly and preferentially stimulated apoptotic cell death of malignant cells (multiple myeloma, non-Hodgkin’s lymphoma and leukemia). Significant synergistic and/or additive tumor cell killing activity has been observed in vitro and in vivo when tumor cells were treated with BL-8040 together with Rituximab, Bortezomib, Imatinib, Cytarabine and the FLT-3 inhibitor AC-220 (in NHL, MM, CML, AML, and AML-FLT3-ITD models, respectively). BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.

About Stem Cell Mobilization

High-dose chemotherapy followed by stem cell transplantation has become an established treatment modality for a variety of hematologic malignancies, including multiple myeloma, as well as various forms of lymphoma and leukemia. Modern peripheral stem-cell harvesting often replaces the use of traditional surgical bone marrow stem-cell harvesting. In the modern method, stem cells are mobilized from the bone marrow using granulocyte colony-stimulating factor (G-CSF), often with the addition of a mobilizing agent such as Plerixafor (Mozobil), harvested from the donor’s peripheral blood by apheresis, and infused to the patient after chemotherapy ablation treatment.

Argos Therapeutics Announces Initiation of a Phase 2 Clinical Trial of AGS-003 for the Treatment of Non-small Cell Lung Cancer in Combination with Standard-of-Care Chemotherapy

On March 23, 2016 Argos Therapeutics, Inc. (Nasdaq:ARGS) ("Argos"), an immuno-oncology company focused on the development and commercialization of truly individualized immunotherapies for the treatment of cancer based on the Arcelis technology platform, reported the initiation of an investigator-sponsored Phase 2 clinical trial of AGS-003 in combination with standard platinum-doublet chemotherapy with or without radiation in patients with newly diagnosed Stage 3 non-small cell lung cancer (NSCLC) (Press release, Argos Therapeutics, MAR 23, 2016, View Source [SID:1234509835]).

The study is being conducted at the Cancer Research Network of Nebraska (CRNN) and is expected to enroll 20 patients. AGS-003 will be administered either concurrently with chemotherapy and with or without radiation or sequentially with chemotherapy and with or without radiation, according to the subject’s assigned treatment arm.

"The standard of treatment of NSCLC has been chemotherapy after surgery, but now we can offer this exciting new option of individualized immunotherapy," said Dr. Stephen Lemon, co-principal investigator and president of Oncology Associates, Omaha, Nebraska, a CRNN collaborating practice. "We are thrilled to participate in this exciting study and are hopeful that AGS-003 will be safe and effective, and help our patients fight this terrible disease."

AGS-003 is an individualized immunotherapy designed to induce a memory T-cell response specific to each patient’s cancer, including the unique tumor mutations (or neoantigens). It is produced using a small sample of RNA from a patient’s own tumor, and dendritic cells derived from a cell collection procedure from the patient.

The research team at CRNN will evaluate the impact of AGS-003 on the toxicity of standard chemotherapy as the primary safety endpoint. Researchers will also measure the activation of memory T-cells in patients who complete the Induction Phase and receive five or more doses of AGS-003 to determine the immunologic response.

"We are excited that this trial has opened for enrollment. This is the first clinical trial of AGS-003 outside of metastatic renal cell carcinoma and we can now explore the potential activity of this novel immunotherapy in other solid tumors. NSCLC is interesting because it is a tumor type reported to have a high number of mutated targets for the immune system, and therefore represents an important opportunity to integrate treatment with AGS-003 during or following standard-of-care chemotherapy," said Lee F. Allen, M.D., Ph.D., chief medical officer at Argos. "The CRNN team is among the most prominent and experienced oncology research groups in the Midwest, and we look forward to their efforts to rapidly advance this important clinical research and expand the potential indications for the use of AGS-003."

To learn more about the clinical trial visit View Source, call 402-697-2229, or send an e-mail to [email protected].

About Lung Cancer

American Cancer Society estimated that in 2016 approximately 224,000 Americans would be diagnosed with lung cancer resulting in nearly 160,000 deaths. It is the second most common cancer and the leading cause of cancer death for men and women; about 1 out of 4 cancer deaths result from lung cancer. Between 85 and 90% of these are non-small cell lung cancer (NSCLC) histology, which includes squamous cell, adenocarcinoma, and large cell (undifferentiated) cancers. Despite early detection screening efforts, the majority of NSCLC patients continue to present with advanced stage disease (Stage III, IV) at the time of diagnosis. The mainstay of treatment for Stage IV NSCLC is limited to systemic therapies.

Expanded IgG Lineages in Lung Cancer Non-Progressors Reveal Anti-Tumor Antibodies

Abstract: Analyzing anti-cancer immune responses is key to understanding cancer immunotherapy mechanisms. We used Immune Repertoire Capture (IRC) technology to sequence the full length variable regions of natively paired immunoglobulin heavy and light chain genes expressed by over 5000 blood plasmablasts (activated B cells) from a patient with Stage 4 lung adenocarcinoma during a period of long term non-progression (2+ years). There was extensive diversity of germline gene usage and elevated levels of somatic hypermutation (SHM) among the individual B cells. Sequences were grouped into putative clonal families based on immunoglobulin gene usage and other sequence features. Over 1500 putative antibody clonal families were identified, including families observed across blood collection time points and similar to families from another lung adenocarcinoma patient. The full length variable regions of IRC sequences were directly gene synthesized to generate recombinant antibodies representing over 150 large and small putative families. Antibodies showed a range of staining patterns on tumor and normal tissues, including some antibodies that bound tumor types other than lung tumor and some that bound tumor much better than normal tissue. Over one third of the antibodies bound lung cancer-derived cell lines. Some antibodies mediated ADCC killing in vitro. Human proteome arrays are being used to identify the targets of the antibodies. Analyses identified clones with differing SHM from the same putative family that bind the same target with varying potencies, indicating that the mutational differences between sibling antibodies reveal structure-activity information.