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Helsinn Group and MEI Pharma Report Prolongation of Survival Results from Phase 2 Clinical Study of Pracinostat and Azacitidine in Acute Myeloid Leukemia

On December 5, 2016 Helsinn, a Swiss pharmaceutical group focused on building quality cancer care products, and MEI Pharma, Inc. (Nasdaq: MEIP), an oncology company focused on the clinical development of novel therapies for cancer, reported final results from a Phase 2 clinical study of the investigational drug candidate Pracinostat and azacitidine in elderly patients with acute myeloid leukemia (AML) who were not eligible for induction chemotherapy, including evidence of prolongation of survival in the overall population and across a number of patient subgroups (Press release, MEI Pharma, DEC 5, 2016, View Source [SID1234516928]).

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In an oral presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting on Saturday, Dr. Guillermo Garcia-Manero, MD Anderson Cancer Center, principal investigator of the study, reported a median overall survival of 19.1 (95%CI: 10.7-26.5) months, one-year survival of 62% and a complete response (CR) rate of 42%.

"The results from this study of Pracinostat and azacitidine in elderly patients deemed unfit for intensive therapy are particularly encouraging," said Dr. Garcia-Manero. "Despite recent advances in the treatment of AML, options for these elderly unfit patients remain limited. The combination of Pracinostat and azacitidine appears to show a long-term survival benefit in this population, including an unprecedented two-year survival rate of 41% in this study. Furthermore, the prolongation of survival over what is generally expected for azacitidine alone is observed not only in the overall population, but across virtually every defined patient subset, including cytogenetic risk group, de novo or secondary AML, age and ECOG performance status."

A copy of the presentation, entitled "A Phase 2 Study of Pracinostat and Azacitidine in Elderly Patients with Acute Myeloid Leukemia (AML) Not Eligible for Induction Chemotherapy: Response and Long-Term Survival Benefit," is available at www.meipharma.com.

The open-label Phase 2 study enrolled a total of 50 patients at 15 centers across the U.S. Median age in the study was 75 years. Patients received 60 mg of Pracinostat orally three times a week for three weeks followed by one week of rest and 75 mg m2 of azacitidine via subcutaneous injection or intravenous infusion for the first seven days of each 28-day cycle. The combination of Pracinostat and azacitidine had no unexpected toxicities. The most common grade 3/4 treatment-emergent adverse events reported in >10% of all patients included thrombocytopenia, febrile neutropenia, neutropenia, fatigue and anemia.

Site recruitment is ongoing for the global Phase 3 study of Pracinostat and azacitidine in newly diagnosed AML patients who are ≥75 years of age or unfit for intensive induction chemotherapy.

About Pracinostat
Pracinostat is a potential best-in-class, oral histone deacetylase (HDAC) inhibitor. The U.S. Food and Drug Administration has granted Breakthrough Therapy Designation for Pracinostat in combination with azacitidine for the treatment of patients with newly diagnosed AML who are ≥75 years of age or unfit for intensive chemotherapy. In August 2016, Helsinn and MEI Pharma entered into an exclusive licensing, development and commercialization agreement for Pracinostat in AML and other potential indications. The deal provides the complementary resources from both organizations to rapidly advance Pracinostat into Phase 3 clinical development and expand into additional indications, including high and very high risk myelodysplastic syndrome (MDS).

Pracinostat is an investigational agent and is not approved for use in the U.S.

About AML
Acute myeloid leukemia (also known as acute myelogenous leukemia) is the most common acute leukemia affecting adults, and its incidence is expected to continue to increase as the population ages. The American Cancer Society estimates about 20,830 new cases of AML per year in the U.S., with an average age of about 67 years. Treatment options for AML remain virtually unchanged for nearly 40 years. Front line treatment consists primarily of chemotherapy, while the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology recommend hypomethylating agents azacitidine or decitabine as low intensity treatment options for AML patients over the age of 60 who are unsuitable for induction chemotherapy.

Celldex Presents Data on CDX-1140, a Novel CD40 Agonist Antibody for Hematologic and Solid Malignancies, at the American Society of Hematology (ASH) Annual Meeting

On December 5, 2016 Celldex Therapeutics, Inc. (NASDAQ:CLDX) reported data on new product candidate CDX-1140, a fully human antibody targeted to CD40 that has demonstrated potent agonist and anti-lymphoma activity (Press release, Celldex Therapeutics, DEC 5, 2016, View Source [SID1234516926]). Found on antigen presenting cells, such as dendritic cells, macrophages and B cells, CD40 is a key activator of the immune response and is expressed on many cancer cells, in particular B cell lymphomas. The data were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting on Saturday, December 3 in a poster titled "CDX-1140, A Novel Agonist CD40 Antibody with Potent Anti-lymphoma Activity" (Abstract #1848). CDX-1140 is expected to be ready to enter clinical studies in patients with advanced cancers, including lymphoma, in 2017.

"We have previously characterized CDX-1140 as possessing a needed balance between its agonist activity and its safety profile to allow for systemic dosing at levels that provide good tissue and tumor penetration, which we believe to be important in order to fully capture the benefit of CD40 immunotherapy," said Tibor Keler, Ph.D., Executive Vice President and Chief Scientific Officer of Celldex Therapeutics. "With this study in preclinical lymphoma tumor models, we show both direct and indirect anti-lymphoma activity as well as synergistic anti-lymphoma activity with our CD27 agonist varlilumab, supporting potential combination treatment in this setting."

The poster features detailed analyses of the anti-lymphoma efficacy of CDX-1140 both as a single-agent and in combination with varlilumab, Celldex’s agonist antibody that binds and activates CD27, or with human immune cells. It is available on the "Publications" page of the "Science" section of the Celldex website. Key findings include:

CDX-1140 elicits direct anti-tumor activity against CD40-positive lymphomas in preclinical tumor models.
The addition of human peripheral blood mononuclear cells (PBMCs) to the tumor models enhances the anti-tumor activity of CDX-1140 compared to the administration of either human PBMC or CDX-1140 alone, indicating an activated anti-tumor immune response by CDX-1140 in addition to direct anti-tumor activity.
The combination of CDX-1140 and varlilumab, elicited greater anti-tumor activity than either antibody alone.
Celldex is currently performing manufacturing and IND-enabling studies to support Phase 1 dose-escalation studies of CDX-1140. The Company believes that the potential for CDX-1140 will be best defined in combination studies with other immunotherapies or conventional cancer treatments.

Additionally, data from investigator sponsored research with varlilumab, CDX-301 and CDX-1401 were/will be presented by Celldex’s collaborating investigators during the ASH (Free ASH Whitepaper) Annual Meeting.

Varlilumab: "Anti-CD27 Enhances Lymphoma Immunotherapy through Profound Myeloid Cell Recruitment" was presented in a poster session on Sunday, December 4 (Abstract #3024). This poster was selected for discussion in a Special-Interest Session called, "Novel Approaches to Immunotherapy — Not Just Checkpoint" to be held on Monday, December 5, 2016 from 12:15-1:15 pm PST.
CDX-301: "Combining In Situ Vaccination with Immune Checkpoint Blockade Induces Long-Term Regression of Lymphoma Tumors" was presented in an oral session on Sunday, December 4 (Abstract #465).

CDX-1401: "Vaccination with NY-ESO-1 in Combination with Decitabine for Patients with MDS" will be presented in a poster session on Monday, December 5 (Abstract #4326)

Aduro Biotech Announces Anti-CD27 Agonist, an Investigational Anti-Cancer Immunotherapy, Advancing in Collaboration with MSD

On December 5, 2016 Aduro Biotech, Inc. (Nasdaq:ADRO), a biopharmaceutical company with three distinct immunotherapy technologies, reported that an anti-CD27 antibody developed by Aduro Biotech Europe and derived from its proprietary B-select technology has been selected to be advanced into clinical development by Merck & Co., Inc., Kenilworth, NJ, USA (known as MSD outside the U.S. and Canada), through a subsidiary (Press release, Aduro BioTech, DEC 5, 2016, View Source [SID1234516924]). CD27 has been recognized as having a critical role in activating a productive anti-cancer immune response and has demonstrated the potential to be combined with checkpoint inhibitors in pre-clinical studies.

"Pre-clinical studies have shown that an anti-CD27 agonist can induce a T cell-mediated anti-cancer immune response, and in combination with PD-1 immune checkpoint inhibitors complete tumor eradication can be achieved," said Hans van Eenennaam, Ph.D., chief operational officer, Aduro Biotech Europe.

The CD27 antibody was licensed by MSD to advance as a part of their successful immunotherapy development program and was identified in close collaboration with Prof. Jannie Borst, Ph.D., professor at the University of Amsterdam and division head at the Netherlands Cancer Institute, through Aduro’s B-select monoclonal antibody technology. This technology includes a proprietary ultra-selective functional screening process to identify antibodies with unique binding properties against a broad repertoire of targets that can modulate the innate and adaptive arms of the immune system.

"In 2014, prior to the acquisition by Aduro Biotech, BioNovion entered into a worldwide license agreement with MSD that covers the product candidate’s development and advancement through commercialization," said Andrea van Elsas, Ph.D., chief scientific officer of Aduro Biotech Europe. "Both companies recognized the significant potential of targeting CD27 as a new and distinct mechanism in cancer immunotherapy, especially in the context of PD-1 checkpoint inhibitors, and were strongly committed to accelerate a quality candidate into the clinic."

Conference Call with Management
Aduro’s management will host a conference call to review this announcement and provide a program update, including STELLAR, today at 5:30 a.m. PT/ 8:30 a.m. ET. To participate in the conference call, please dial (844) 309-0604 (domestic) or (574) 990-9932 (international) and refer to conference ID 31336163. Live audio of the conference call will be simultaneously webcast and will be available to members of the news media, investors and the general public at View Source

About the Aduro – MSD Collaboration
BioNovion B.V. and MSD, through a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, entered into a worldwide license agreement in 2014 for the development and commercialization of CD27 antibody agonists, and BioNovion received an up-front payment of $15 million. In 2015, BioNovion was acquired by Aduro Biotech and became its subsidiary, Aduro Biotech Europe B.V.

Under the agreement, a Joint Research Committee was formed to advance the program. Aduro has been reimbursed for certain research activities and is eligible to receive future development, commercial and net sales milestone payments. In addition, Aduro is eligible to receive royalties in the mid-single digits to low teens based on any net sales of the product, if it is approved for marketing.

Adaptimmune Announces Initiation of Myxoid/Round Cell Liposarcoma Study

On December 5, 2016 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, reported that it has initiated a study of its NY‑ESO SPEAR T‑cells in myxoid/round cell liposarcoma (MRCLS) (Press release, Adaptimmune, DEC 5, 2016, View Source [SID1234516923]). Patient screening is underway, and the results from this study in up to 15 patients will inform a potential future registration trial. The initiation of screening in this study meets a milestone set forth in the Company’s strategic collaboration agreement with GlaxoSmithKline plc (LSE/NYSE: GSK).

This is an open-label pilot study in patients to assess preliminary safety and efficacy in this new indication. Initially, 10 patients will be enrolled. If further characterization of the treatment is required, up to 5 additional patients may be enrolled. Eligible patients will be HLA-A*02:01, HLA‑A*02:05 and/or HLA-A*02:06 with advanced (metastatic or inoperable) high grade MRCLS whose tumor shows positive NY-ESO-1 expression defined as ≥30 percent of cells that are 2+ or 3+ by immunohistochemistry. Patients will receive preconditioning with fludarabine and cyclophosphamide at the same dose that is being used in Cohort 4 of the Company’s ongoing synovial sarcoma study.

About MRCLS
Soft tissue sarcomas can develop from tissues like fat, muscle, nerves, fibrous tissues, blood vessels, or deep skin tissues. There are approximately 50 types of soft tissue sarcomas, including MRCLS. Myxoid/round cell liposarcoma is associated with specific chromosomal translocations and represents about 30 to 35 percent of liposarcomas and 5 to 10 percent of all adult soft tissue sarcomas. Myxoid/round cell liposarcoma commonly presents at an age ranging from 35 to 55 years.

Sunesis Pharmaceuticals Announces Presentation of Results from Completed Phase 1A Healthy Volunteer Study Evaluating Oral Non-Covalent BTK inhibitor SNS-062 at ASH Annual Meeting

On December 5, 2016 Sunesis Pharmaceuticals, Inc. (Nasdaq:SNSS) reported the presentation of results from the Company’s Phase 1A study in healthy volunteers evaluating oral non-covalent reversible BTK inhibitor SNS-062 (Press release, Sunesis, DEC 5, 2016, View Source [SID1234516922]). The results were presented in a poster session titled "CLL: Therapy, excluding Transplantation: Poster I" on Saturday, December 3, at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego, California. The presentation, titled "First-in-Human Phase 1a Study of the Safety, Pharmacokinetics, and Pharmacodynamics of the Noncovalent Bruton’s Tyrosine Kinase (BTK) Inhibitor SNS-062 in Healthy Subjects," is available at www.sunesis.com.

"These final results from the Phase 1A Healthy Volunteer study suggest that SNS-062, with a favorable safety, pharmacokinetic (PK) and pharmacodynamic (PD) profile, and its improved PK properties over ibrutinib and acalabrutinib, has significant potential to become a new treatment option for patients with B-cell malignancies," said Linda Neuman, M.D., Vice President, Clinical Development of Sunesis. "Additionally, as a non-covalent BTK inhibitor with a distinct reversible binding profile, SNS-062 may overcome the acquired resistance to ibrutinib and other covalent clinical-stage BTK inhibitors resulting from a point mutation (C481S) in the active site."

"The safety profile, extent of SNS-062 exposure, and duration of BTK inhibition from these study results are encouraging and support our plans for a Phase 1B/2 study to assess safety and efficacy in patients with advanced B-cell malignancies after prior ibrutinib exposure, both with and without a BTK C481 mutation," said Daniel Swisher, President and Chief Executive Officer of Sunesis. "We are preparing an IND filing for this year as we work closely with our identified clinical sites for this study, and expect to begin dosing patients within the first half of 2017."

The reported data from this Phase 1A randomized, double-blind, placebo-controlled, single-dose study are from four sequential cohorts of 8 subjects each who were randomly assigned to receive progressively higher single oral administrations of SNS-062 at doses of 25, 50, 100, 200, and 300 mg (n=6 per cohort) or placebo (n=2 per cohort).

For the primary endpoint of safety in stage 1, investigators were blinded to treatment arm for assessment of relatedness. Overall, AEs were reported for 8 (33%) subjects who received SNS-062 and for 3 (38%) subjects who received placebo. In the unblinded stages 2 and 3 of the trial, a similar pattern and rate of AEs were observed. Overall, no obvious pattern of dose-dependent toxicity was observed. All AEs were transient and low grade. None of the AEs, laboratory abnormalities, or ECG or telemetry findings were considered clinically meaningful. No SAEs were reported.

SNS-062 was rapidly absorbed and had mean plasma half-life values across all dose cohorts of 6.9 to 17 hours. SNS-062 demonstrated rapid, profound (~100%), and prolonged inhibition of BTK at all dose levels support investigation of a twice-daily dosing regimen in B-cell malignancies with or without an acquired BTK resistance mutation.

Furthermore in stage 2, food had no impact on the extent of absorption or elimination of SNS-062, suggesting that it may be administered to patients without regard to food. In stage 3, SNS-062, similar to ibrutinib, is a sensitive substrate of CYP3A4 and administration with moderate/strong CYP3A4 inhibitors or inducers is not recommended.

About SNS-062

SNS-062 is a novel, second-generation BTK inhibitor, a class of kinase inhibitors that selectively inhibits the enzyme Bruton’s tyrosine kinase (BTK). This target mediates signaling through the B-cell receptor, which is critical for adhesion, migration, proliferation and survival of normal and malignant B-lineage lymphoid cells. Unlike other drugs in its class, SNS-062 binds non-covalently and reversibly to the BTK enzyme. Its binding profile along with improved PK/PD properties potentially provide SNS-062 an opportunity to address the leading acquired resistance to ibrutinib, a mutation in the enzyme’s binding site required for covalent binding. In preclinical studies, SNS-062 demonstrated potent activity against C481S mutated B-cell malignancies, and has been studied in healthy subjects in a completed Phase 1A, randomized, double-blind, placebo-controlled dose-ranging study to investigate the drug’s safety, pharmacokinetics, and pharmacodynamics. With the reported successful study outcome, SNS-062 is proceeding to a Phase 1B/2 study in patients with B-cell malignancies.