On November 30, 2015 Ignyta, Inc. (Nasdaq: RXDX), a precision oncology biotechnology company, and the European Organisation for Research and Treatment of Cancer (EORTC) reported that they will collaborate via EORTC’s Screening Patients for Efficient Clinical Trial Access (SPECTA) biomarker screening initiative to identify patients who harbor a gene rearrangement to NTRK1, NTRK3, ROS1 or ALK and therefore may be eligible for Ignyta’s global STARTRK-2 Phase 2 clinical study (Press release, Ignyta, NOV 30, 2015, View Source [SID:1234508358]). Schedule your 30 min Free 1stOncology Demo! This study is evaluating entrectinib, Ignyta’s novel, orally available, selective tyrosine kinase inhibitor targeting tumors that harbor activating alterations to these genes. Under the collaboration between SPECTA and Ignyta, eligible patients testing positive for a gene rearrangement to NTRK1, NTRK3, ROS1 or ALK are to be exclusively recommended for enrollment in the STARTRK-2 clinical trial.
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
SPECTA is a pan-European clinical trial site and cancer patient molecular screening network established by EORTC in collaboration with more than 30 leading cancer treatment centers in 11 European countries to provide efficient access for patients to molecularly driven clinical trials. Tissue samples from cancer patients being treated at SPECTA institutions throughout Europe are sent to the SPECTA program central laboratory at 14M Genomics, a spin-out of the Wellcome Trust Sanger Institute, for molecular genetic analysis. The collaboration will focus initially on SPECTA’s currently active programs to screen patients with colorectal cancer (SPECTAcolor) and lung cancer (SPECTAlung) and will expand to include additional tumor types in the future as additional SPECTA cohorts become activated. The collaboration will extend throughout the accrual phase of the STARTRK-2 study.
"Since we first initiated dialog with the leadership of the EORTC SPECTA initiative a year-and-a-half ago, we have shared their vision to conduct efficient biomarker-driven clinical trials of innovative new cancer medicines," said Jonathan Lim, M.D., Chairman and CEO of Ignyta. "We are honored to be selected by EORTC as the first biopharmaceutical partner for the SPECTA initiative and see this collaboration as an opportunity to help cancer patients throughout Europe by matching patients with certain biomarker signatures to a targeted treatment option."
Denis Lacombe, M.D., EORTC Headquarters Director, added, "SPECTA is a unique model of partnership as it connects all stakeholders involved in drug development, enhancing joint expertise to benefit patients. We look forward to working with Ignyta to leverage the SPECTA infrastructure to study entrectinib in patients with potentially relevant molecular alterations."
About Entrectinib
Entrectinib is a novel, orally available, selective tyrosine kinase inhibitor targeting tumors that harbor activating alterations to NTRK1/2/3 (encoding TrkA/ TrkB/TrkC), ROS1 or ALK. Entrectinib is the most potent Trk inhibitor in the clinic, without undesirable off-target activity, and the only Trk inhibitor with clinically demonstrated activity against CNS metastases. This product candidate is in a Phase 2 clinical trial called STARTRK-2, which is the second of the "Studies of Tumor Alterations Responsive to Targeting Receptor Kinases." The trial is a global, multicenter, open label, potentially registration-enabling Phase 2 clinical trial of entrectinib that utilizes a basket design with screening of patient tumor samples for the relevant targets. Such a basket design takes full advantage of entrectinib’s demonstrated preliminary clinical activity across a range of different tumor types and molecular targets.
Kura Oncology Announces First Patient Dosed in an Investigator-Sponsored Phase 2 Trial of Tipifarnib in Patients With HRAS Mutant Urothelial Cancer
On November 30, 2015 Kura Oncology, Inc. (NASDAQ:KURA), reported that the first patient has been dosed in an investigator-sponsored Phase 2 trial of its lead drug candidate, tipifarnib, an inhibitor of protein farnesylation, in cancer patients with urothelial carcinoma tumors characterized by HRAS mutations (Press release, Kura Oncology, NOV 30, 2015, View Source [SID:1234508355]). The study is being conducted under the direction of Se Hoon Park, M.D., Ph.D. in the Division of Hematology-Oncology at the Samsung Medical Center in Seoul, South Korea. Schedule your 30 min Free 1stOncology Demo! "This study, in combination with our ongoing Phase 2 study in HRAS mutant tumors, should provide further insight into tipifarnib’s activity in HRAS mutant tumors and broaden our understanding of its mechanism of action," said Antonio Gualberto, M.D., Ph.D., Chief Medical Officer of Kura Oncology. "We are pleased to support the efforts of Dr. Park and his colleagues at the Samsung Medical Center."
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"The development of new drugs for patients with refractory urothelial cancer is an important unmet medical need," said Dr. Park, lead investigator of the study. "There is a compelling scientific rationale to evaluate the role of HRAS and the activity of tipifarnib in this setting."
The primary objective of the Phase 2 study is to investigate the antitumor activity, in terms of objective response rate, of tipifarnib in patients with locally advanced, unresectable or metastatic, relapsed and/or refractory urothelial cancer tumors that carry HRAS mutations. Secondary objectives include evaluation of progression-free survival, duration of response and safety. It is planned that the study will enroll up to 18 patients.
About HRAS
The HRAS protein is a GTPase involved in regulating cell division in response to growth factor stimulation. Growth factors act by binding cell surface receptors that span the cell’s plasma membrane. Once activated, receptors stimulate signal transduction events in the cytoplasm, a process by which proteins and second messengers relay signals from outside the cell to the cell nucleus and instruct the cell to grow or divide. HRAS is an early player in many signal transduction pathways.
HRAS acts as a molecular on/off switch. Once it is turned on, it recruits and activates proteins necessary for the propagation of the receptor’s signal. In certain tumors, mutations in HRAS or its upstream effectors cause it to be permanently on, resulting in persistent activation of downstream growth and proliferation signals that drive tumor cell growth. Farnesyl transferase inhibitors (FTIs), such as tipifarnib, work to prevent the aberrant growth and proliferation of cells that are dependent on these signaling pathways by switching HRAS off.
Trial Rationale
The development of new drugs for patients with refractory urothelial cancer represents an important unmet medical need. Although the expression of HRAS in bladder tumors has been reported to have an inverse correlation with recurrence and disease progression, no data are yet available on the prognostic value of HRAS mutation in this indication. However, the strong association between Costello syndrome and bladder cancer may implicate HRAS in bladder carcinogenesis.
About Tipifarnib
Kura Oncology’s lead drug candidate, tipifarnib, inhibits farnesylation, a key cell signaling process implicated in cancer initiation and development. In extensive clinical trials, tipifarnib has shown compelling and durable anti-cancer activity in certain patient subsets and a well-established safety profile. Preclinical and clinical data suggest that, in the right genetic context, tipifarnib has the potential to provide significant benefit to cancer patients with limited treatment options. Leveraging advances in next-generation sequencing as well as emerging information about cancer genetics, Kura Oncology will seek to identify patients most likely to benefit from tipifarnib. In addition to the currently ongoing Phase 2 clinical trial of tipifarnib in patients with tumors characterized by HRAS mutations, the company initiated a Phase 2 clinical trial in patients with peripheral T-cell lymphomas in the third quarter of 2015. Kura Oncology holds an exclusive license to develop and commercialize tipifarnib in the field of oncology, under an agreement with Janssen Pharmaceutica NV.
Lung cancer experts call for improved EGFR mutation testing to allow all eligible NSCLC patients access to personalised treatment
On November 30, 2015 Boehringer Ingelheim reported insights from experts working on-the-ground in lung cancer, compiled by Boehringer Ingelheim, shed light on challenges faced by patients with advanced stage adenocarcinoma, a type of non-small cell lung cancer (NSCLC), in being tested for EGFR mutations, leaving some without access to the most appropriate treatment for them (Press release, Boehringer Ingelheim, NOV 29, 2015, View Source [SID:1234508356]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
A new insights report sees healthcare professionals and patient group representatives reflect on existing gaps in nationwide EGFR testing, which should be conducted for eligible patients upon diagnosis according to guidelines.1
Dr Matthew Peters, Professor of Respiratory Medicine, Macquarie University Australia and Chair, Global Lung Cancer Coalition commented, "Whilst country-level insights within this report do vary, common barriers to achieving EGFR testing and personalised treatment for all eligible patients are clear. Education is key: for patients, healthcare professionals and the wider community. More is needed to bring us closer to helping each and every NSCLC patient receive the right treatment for them."
Country-level themes identified by experts from Western Europe and North America include:
Germany: insufficient reimbursement for mutation tests impacts EGFR testing rates for inpatients (majority of patients are diagnosed in an inpatient setting)
Italy: high number of patients are tested for EGFR mutations, but some patients and caregivers ask to start first-line treatment before receiving test results
Spain: many cancer centres are currently achieving high EGFR testing rates, but disparity exists as some centres are increasingly impacted by the growing economic crisis
UK: despite high levels of EGFR testing, some patients start treatment before results of this testing are available, so treatment is not personalised for their mutation
Canada: a healthcare system which is publically funded through each province and territory brings forth challenges in ensuring all eligible patients across the country are EGFR tested at diagnosis
USA: a substantial percentage of treatment decisions are not based on EGFR mutation subtype resulting in patients not receiving the most appropriate personalised treatment plans
Experts unite with a shared vision where all eligible NSCLC patients have the most appropriate diagnostic tests and access to personalised treatment. Common barriers holding back the realisation of this vision include difficulties in obtaining adequate tumour tissue samples to test, and delays in receiving test results. This is important as data have shown that EGFR targeted treatments significantly delay disease progression when compared to chemotherapy. For a specific targeted therapy, extended overall survival of patients with the most common type of mutation (del19) when compared to chemotherapy has also been observed.2
Dr Mehdi Shahidi, Medical Head, Solid Tumour Oncology, Boehringer Ingelheim added, "EGFR testing rates have improved dramatically over recent years, but there is still work to be done. Targeted therapies can benefit patients with EGFR mutation-positive lung cancer by delaying disease progression and for some, offering survival advantages compared to chemotherapy. This is why EGFR mutation testing and acting on the results of these tests is so important. Healthcare teams need to optimise the tools, resources and tests available to improve access to personalised treatment, for the ultimate benefit of patients."
Novartis highlights clinical advances at ASH 2015, underscoring leadership in hematology research
On November 30, 2015 Novartis reported that it will demonstrate the strength of its research program and portfolio at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Novartis, NOV 29, 2015, View Source [SID:1234508354]). Presentations will highlight data across leukemias, lymphomas and myelomas as well as supportive care, including key findings in rare and difficult-to-treat patient populations, in addition to personalized cell therapies. The ASH (Free ASH Whitepaper) Annual Meeting will be held December 5-8 in Orlando, Florida.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"We pride ourselves in our drive for new science and innovation, and look forward to bringing this promise to life at ASH (Free ASH Whitepaper) through the results of our latest hematology research," said Bruno Strigini, President, Novartis Oncology. "We will be presenting encouraging overall survival data for both investigational and approved products, underscoring our commitment to improve and extend people’s lives."
A key focus in hematology for Novartis is developing therapies for rare and difficult-to-treat patient populations. The acute myeloid leukemia (AML) community in particular is in need of new treatment options as the general therapeutic strategy has remained unchanged for more than 25 years[1],[2]. Further, about one-third of AML patients harbor a FLT3 mutation, which is associated with poorer prognoses than in those without the mutation[3],[4]. To this end, key data on PKC412 (midostaurin) from the following two studies will be presented:
The Multi-Kinase Inhibitor Midostaurin (M) Prolongs Survival Compared with Placebo (P) in Combination with Daunorubicin (D)/Cytarabine (C) Induction (ind), High-Dose C Consolidation (consol), and As Maintenance (maint) Therapy in Newly Diagnosed Acute Myeloid Leukemia (AML) Patients (pts) Age 18-60 with FLT3 Mutations (muts): An International Prospective Randomized (rand) P-Controlled Double-Blind Trial (CALGB 10603/RATIFY [Alliance]) (Abstract #6, Plenary Session, Sunday, December 6, 2:00 – 4:00 pm EST)
Midostaurin in Combination with Intensive Induction and As Single Agent Maintenance Therapy after Consolidation Therapy with Allogeneic Hematopoietic Stem Cell Transplantation or High-Dose Cytarabine (NCT01477606) (Abstract #322, Oral Presentation, Sunday, December 6, 5:15 pm EST)
Novartis and the University of Pennsylvania’s Perelman School of Medicine (Penn) have an exclusive global collaboration to research, develop and commercialize chimeric antigen receptor (CAR) T cell therapies for the investigational treatment of cancers. New data on investigational CART therapy CTL019, as well as cell processing technology will be presented at ASH (Free ASH Whitepaper) including:
Durable Remissions in Children with Relapsed/Refractory ALL Treated with T Cells Engineered with a CD19-Targeted Chimeric Antigen Receptor (CTL019) (Abstract #681, Oral Presentation, Monday, December 7, 3:15 pm EST)
Sustained Remissions Following Chimeric Antigen Receptor Modified T Cells Directed Against CD19 (CTL019) in Patients with Relapsed or Refractory CD19+ Lymphomas (Abstract #183, Oral Presentation, Sunday, December 6, 8:00 am EST)
Successful Translation of Chimeric Antigen Receptor (CAR) Targeting CD19 (CTL019) Cell Processing Technology from Academia to Industry (Abstract #3100, Poster Presentation, Sunday, December 6, 6:00 – 8:00 pm EST)
Novartis will share new research for pipeline compound ABL001, a small molecule designed to inhibit BCR-ABL. ABL001 is different from Glivec (imatinib)* and Tasigna (nilotinib) as it binds to a unique region of BCR-ABL, forcing a conformational change that disables the protein’s active site. As part of Novartis’ ongoing commitment to chronic myeloid leukemia (CML) research, ABL001 represents the company’s evolving science and is being investigated in Phase I trials:
ABL001, a Potent, Allosteric Inhibitor of BCR-ABL, Exhibits Safety and Promising Single- Agent Activity in a Phase I Study of Patients with CML with Failure of Prior TKI Therapy (Abstract #138, Oral Presentation, Saturday, December 5, 5:15 pm EST)
Novartis will also be presenting safety and efficacy data, including long-term studies, at ASH (Free ASH Whitepaper) from its approved hematological treatments:
Jakavi (ruxolitinib)**
Long-Term Efficacy and Safety in COMFORT-II, a Phase 3 Study Comparing Ruxolitinib with Best Available Therapy for the Treatment of Myelofibrosis: 5-Year Final Study Results (Abstract #59, Oral Presentation, Saturday, December 5, 10:30 am EST)
Safety and Efficacy of Ruxolitinib in an 1869-Patient Cohort of JUMP: An Open-Label, Multicenter, Single-Arm, Expanded-Access Study in Patients with Myelofibrosis (Abstract #2799, Poster Presentation, Sunday, December 6, 6:00 – 8:00 pm EST)
Demographics, Baseline (BL) Characteristics, and Disease Symptom Burden in RESPONSE-2: A Randomized, Phase 3 Study of Ruxolitinib in Polycythemia Vera Patients (pts) Who Are Resistant to or Intolerant of Hydroxyurea (HU) (Abstract #2807, Poster Presentation, Sunday, December 6, 6:00 – 8:00 pm EST)
Continued Treatment With Ruxolitinib Provides Additional Hematocrit Control and Spleen Volume Responses in Patients with PV Treated in the RESPONSE Study (Abstract #2804, Poster Presentation, Sunday, December 6, 6:00 – 8:00 pm EST)
Tasigna (nilotinib)
Dose-Optimized Nilotinib (NIL) in Patients (pts) with Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP): Final results from ENESTxtnd study (Abstract #344, Oral Presentation, Sunday, December 6, 4:45 pm EST)
Impact of Age on Efficacy and Toxicity of Nilotinib in Patients with Chronic Myeloid Leukemia in Chronic Phase (CML-CP): ENEST1st Sub-Analysis (Abstract #479, Oral Presentation, Monday, December 7, 8:00 am EST)
International Scale (IS)-Standardized BCR-ABL1 Digital Polymerase Chain Reaction (dPCR) Assays Using ABL1, BCR, and GUS Control Genes for Measuring Deep Molecular Response (MR) in Chronic Myeloid Leukemia (CML) (Abstract #136, Oral Presentation, Saturday, December 5, 4:45 pm EST)
Quantification of BCR-ABL with Digital PCR Results in a Significantly Lower Rate of Deep Molecular Response when Compared to RT-qPCR in CML Patients Treated in the ENEST1st Trial (Abstract #135, Oral Presentation, Saturday, December 5, 4:30 pm EST)
Farydak (panobinostat)
Final Analysis of Overall Survival from the Phase 3 Panorama 1 Trial of Panobinostat Plus Bortezomib and Dexamethasone Versus Placebo Plus Bortezomib and Dexamethasone in Patients with Relapsed or Relapsed and Refractory Multiple Myeloma (Abstract #3026, Poster Presentation, Sunday, December 6, 6:00 – 8:00 pm EST)
Analysis of Outcomes Based on Response in Patients with Relapsed or Relapsed and Refractory Multiple Myeloma Treated with Panobinostat or Placebo in Combination with Bortezomib and Dexamethasone in the Panorama 1 Trial: Updated Analysis Based on Prior Treatment (Abstract #4230, Poster Presentation, Monday, December 7, 6:00 – 8:00 pm EST)
In addition, Sandoz, a Novartis company and the global leader in biosimilars, will present data from PROTECT 2, one of their pivotal Phase III trials investigating use of their proposed pegfilgrastim biosimilar in patients with chemotherapy-induced neutropenia.
Proposed Biosimilar Pegfilgrastim (LA-EP2006) and Reference Pegfilgrastim for the Prevention of Neutropenia in Patients with Breast Cancer: A Randomized, Double-Blind Trial. PROTECT 2: Pegfilgrastim Randomized Oncology (supportive care) Trial to Evaluate Comparative Treatment Results (Abstract #632, Oral Presentation, Monday, December 7, 10:45 am EST)
Throughout ASH (Free ASH Whitepaper) 2015, Novartis Oncology will host dedicated content on the company website (View Source) that will feature unique insights and perspectives on emerging areas of cancer care and research.
Product Information
Approved indications for products vary by country and not all indications are available in every country. The product safety and efficacy profiles have not yet been established outside the approved indications. Because of the uncertainty of clinical trials, there is no guarantee that compounds will become commercially available with additional indications.
For full prescribing information, including approved indications and important safety information about marketed products, please visit
View Source
Because PKC412 (midostaurin), CTL019 and ABL001 are investigational compounds, the safety and efficacy profiles have not yet been fully established. Access to these investigational compounds is available only through carefully controlled and monitored clinical trials. These trials are designed to better understand the potential benefits and risks of the compound. Because of the uncertainty of clinical trials, there is no guarantee that PKC412 (midostaurin), CTL019 and ABL001 will ever be commercially available anywhere in the world.
Co-D Therapeutics Granted Orphan Designation for Triolimus for the Treatment of Angiosarcoma
On April 28, 2015 Co-D Therapeutics, Inc., a pre-clinical stage pharmaceutical company developing agents for the treatment of cancer, reported that the U.S. Food and Drug Administration (FDA) has granted Co-D’s request for orphan drug designation of Triolimus for the treatment of the highly lethal malignancy, angiosarcoma (Press release, Co-D Therapeutics, 28 11, 2015, View Source [SID1234516124]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"We are pleased that Triolimus has been designated an orphan drug for the treatment of angiosarcoma," commented Dr. Kevin Kozak, co-founder and Chief Medical Officer of Co-D Therapeutics. "With few effective options, new agents for angiosarcoma treatment are urgently required. The orphan designation reflects both the FDA’s and Co-D’s commitment to addressing the unmet clinical needs of patients with rare diseases like angiosarcoma."
The Orphan Drug Act provides for economic incentives to encourage the development of drugs for diseases affecting fewer than 200,000 people in the United States. Orphan drug designation will entitle Co-D to seven years of market exclusivity for Triolimus as a treatment for angiosarcoma following marketing approval by the FDA. Additional benefits include tax credits related to clinical trial expenses, potential exemption from the FDA-user fee, assistance in clinical trial design, and smaller trials required for new drug applications.
"The designation of Triolimus as an orphan-drug for angiosarcoma treatment is an early and critical milestone and will facilitate progress through the clinical and regulatory development process," said Abdalla Saad, co-founder and Chief Executive Officer of Co-D Therapeutics. "We find our preclinical data compelling and are thrilled the FDA judged Triolimus meritorious of orphan-drug designation."
Triolimus technology was developed by Prof. Glen Kwon at the University of Wisconsin-Madison. "We are excited to continue the enormously rewarding process of advancing Triolimus to the clinic," said co-founder and Chief Scientific Officer Prof. Kwon.
Triolimus’ intellectual property portfolio will be licensed from the Wisconsin Alumni Research Foundation (WARF). Funding from WARF’s Accelerator Program supported pre-clinical development of Triolimus.
About Angiosarcoma
Angiosarcoma is a rare, aggressive malignancy of endothelial cell differentiation that has a propensity for both local recurrence as well as regional and distant metastases. Long-term disease-free survival is achieved in only half of patients who present with apparently localized disease. Average survival in patients who present with distant disease is less than one year. This poor survival is, in large part, attributable to a dearth of currently available, effective treatment options.
About Triolimus
Triolimus is a novel "3-in-1" nanoparticle that contains three proven anti-cancer agents in a non-toxic carrier. Triolimus is designed to be superior to currently available chemotherapies through both the elimination of toxic excipients often required for intravenous use and through the delivery of three, complementary drugs to maximize anti-cancer effects.