On October 12, 2016 Celgene Corporation (NASDAQ:CELG) and Agios Pharmaceuticals, Inc. (NASDAQ:AGIO) reported each company has entered into collaboration agreements with Abbott (NYSE: ABT), a leader in diagnostic technologies, to develop and commercialize companion diagnostic tests on Abbott’s m2000 RealTime System to identify isocitrate dehydrogenase (IDH) mutations in acute myeloid leukemia (AML) patients (Press release, Agios Pharmaceuticals, OCT 12, 2016, View Source [SID1234515759]). Celgene is currently developing enasidenib (AG-221/CC-90007), an IDH2 mutant inhibitor, for the treatment of patients with relapsed or refractory AML who have an IDH2 mutation. Agios is developing AG-120, an IDH1 mutant inhibitor, for the treatment of patients with relapsed or refractory AML who have an IDH1 mutation. Schedule your 30 min Free 1stOncology Demo! IDH1 and IDH2 mutations occur in approximately 20% of AML patients. An article published online this week in the journal Leukemia (Medeiros, Leukemia 2016) concluded that advances in the understanding of the genetics underlying myeloid malignancies are driving an era of development for targeted treatments such as IDH mutant inhibitors. The authors recommend that IDH mutational analysis should become part of the routine AML diagnostic workup and repeated at relapse to identify patients who may be eligible for targeted investigational treatments currently under clinical study.
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"AML is a complex and heterogeneous disease, making it difficult to treat," said Han Myint, M.D., Vice President, Global Medical Affairs, Myeloid for Celgene. "IDH mutations lead to aberrant DNA methylation, causing a block in myeloid differentiation that leads to disease progression. Molecular profiling is important to identify genomic mutations which may have prognostic and potential treatment implications for patients with AML."
Abbott’s m2000rt RealTime System, is a polymerase chain reaction (PCR) instrument designed to enable clinical laboratories to automate PCR and results analysis, simplifying the complex and manual steps often associated with molecular diagnostics. Both Celgene and Agios have incorporated this screening into clinical trial designs, including the recently initiated Phase 3 IDHENTIFY trial comparing enasidenib with conventional therapy in older patients with an IDH2 mutation and relapsed or refractory AML (NCT02577406).
"The field of personalized medicine is advancing at a rapid pace for a broad range of medical conditions, especially within hematology-oncology," said Chris Bowden, M.D., chief medical officer at Agios. "Our collaboration with Abbott will provide a test to help identify AML patients with IDH mutations who are in need of treatment options."
The m2000 system has not been FDA cleared or approved for use with enasidenib or AG-120.
Enasidenib and AG-120 have not been approved for any use in any country.
Author: [email protected]
Daiichi Sankyo and Dana-Farber Cancer Institute Announce Lung Cancer Research Collaboration
On October 12, 2016 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) and the Dana-Farber Cancer Institute reported a preclinical research collaboration focused on lung cancer (Press release, Daiichi Sankyo, OCT 11, 2016, View Source [SID:SID1234515767]).
A team of scientists led by Pasi A. Jänne, M.D., Ph.D., Director, Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute; Scientific Director, Belfer Center for Applied Cancer Science; and, Professor of Medicine, Harvard Medical School will partner with Daiichi Sankyo on the development of a translational pharmacology package with unique experimental animal and patient derived xenograft models that were established at Dana-Farber Cancer Institute. The collaboration will leverage the translational medicine expertise of the Belfer Center. Financial terms of the agreement were not disclosed.
"We are excited to enter into this unique partnership with Daiichi Sankyo. Working together we can accelerate the development of new therapeutic strategies for patients with lung cancer," said Dr. Jänne.
"Despite several recent significant advances in the treatment of lung cancer with EGFR mutations,many patients still die of this disease, hence our urgency and obligation to pursue swiftly great science," said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo. "By partnering with scientists at Dana-Farber, we are looking to better understand drivers of disease as well as initial and secondary resistance to established targeted treatments with the ultimate goal of identifying a potential new treatment for patients with lung cancer."
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Daiichi Sankyo Announces First Patient Enrolled in Phase 3 QuANTUM-First Trial Investigating Quizartinib in Newly-Diagnosed FLT3-ITD+ Acute Myeloid Leukemia
On October 11, 2016 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that the first patient has been enrolled in the global phase 3 QuANTUM-First study evaluating the oral FLT3-ITD inhibitor quizartinib in patients with newly-diagnosed FLT3-ITD-positive (+) acute myeloid leukemia (AML) (Press release, Daiichi Sankyo, OCT 11, 2016, View Source [SID:SID1234515762]).
QuANTUM-First is a randomized, double-blind, placebo-controlled study evaluating quizartinib in combination with induction and consolidation chemotherapy and as maintenance monotherapy in patients with newly-diagnosed FLT3-ITD+ AML. The primary endpoint of the study is event-free survival. Secondary endpoints include overall survival, complete remission rate, composite complete remission rate and the percentage of subjects achieving a complete remission with no evidence of minimal residual disease.
Approximately 30 percent of patients with AML have a genetic mutation called FLT3-ITD, which is associated with more aggressive disease, resulting in increased relapse rate and reduced overall survival compared to those without this mutation.1FLT3-ITD mutations are more common than FLT3-TKD mutations, which occur in approximately 10 percent of AML patients.1There is controversy as to whether FLT3-TKD mutations carry as poor a prognosis as FLT3-ITD mutations.1Currently, there are no approved targeted treatments for FLT3-ITD+ AML, with little change in the treatment of AML for the past 30 years.2
"It is well established that patients with FLT3-ITD mutated AML have an overall worse prognosis compared to those without this specific mutation," said Harry Erba, MD, PhD, Chair of the QuANTUM-First Steering Committee and Professor of Medicine and Director of the Hematologic Malignancy Program at the University of Alabama at Birmingham. "In this study we are evaluating whether adding quizartinib to standard first-line chemotherapy will help delay or prevent relapse, which in turn may impact overall survival in patients with FLT3-ITD+ AML."
"Given the high unmet need in FLT3-ITD+ AML, we are moving forward with a comprehensive clinical development program investigating the role of quizartinib in multiple lines of treatment including induction and consolidation chemotherapy, maintenance therapy and salvage therapy," said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo. "Additionally, we also are looking to combine quizartinib with other investigational agents in our pipeline such as our MDM2 and BRD4 inhibitors where science suggests combining different mechanisms of action may help improve outcomes."
QuANTUM-First is expected to enroll more than 500 patients between 18 and 75 years of age in the Americas, Europe and Asia-Pacific. More information about the study is available at ClinicalTrials.gov or www.QuantumFirstStudy.com.
About Acute Myeloid Leukemia (AML)
Acute myeloid leukemia (AML) is the most common type of acute leukemia accounting for about 33 percent of all new cases of leukemia.3 An aggressive blood and bone marrow cancer, AML causes uncontrolled growth and accumulation of malignant white blood cells that fail to function normally and interfere with the production of normal blood cells. 3 The five-year survival rate of AML is approximately 26 percent, which is the lowest of all leukemias.3
About Quizartinib
Quizartinib is an investigational oral small molecule that potently and selectively inhibits FLT3-ITD (FMS-like tyrosine kinase-3-internal tandem duplication), which is a growth driver of abnormal cells that contribute to the development of AML.4 Quizartinib has been granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) for the treatment of AML. Quizartinib also has been granted Fast Track Designation by the FDA for the treatment of relapsed/refractory AML. Quizartinib has not been approved by any regulatory authority for uses under investigation.
In addition to QuANTUM-First, a global, randomized, open-label, phase 3 study called QuANTUM-R is evaluating quizartinib as monotherapy in patients with FLT3-ITD+ AML who are refractory to or have relapsed after first-line treatment with or without hematopoietic stem cell transplant (HSCT). The primary objective of QuANTUM-R is to determine whether quizartinib prolongs overall survival compared to salvage chemotherapy, and the secondary objective is to determine event-free survival. The trial is expected to enroll approximately 363 patients age 18 or older in North America, Europe and Asia-Pacific. More information about QuANTUM-R is available at www.QuantumRStudy.com or ClinicalTrials.gov.
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Tolero Pharmaceuticals to Present at the International Conference on Leukemia and Hematologic Oncology in Rome, Italy
On October 11, 2016 Tolero Pharmaceuticals, Inc., a clinical-stage pharmaceutical company developing treatments for oncology and hematological diseases, reported that David J. Bearss, Ph.D., Chief Executive Officer, is scheduled to present the keynote address at the International Conference on Leukemia and Hematologic Oncology, which is being held from October 17-18, 2016 in Rome, Italy (Company Pipeline, Tolero Pharmaceuticals, OCT 11, 2016, View Source [SID:SID1234515757]). The address titled "Sequential Treatment of AML patients with Alvocidib followed by Cytarabine and Mitoxantrone is highly effective through a mechanism dependent on MCL-1 expression and functions" will take place on October 17, 2016 at 10:00 AM CET.
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Steve Warner, Ph.D., Vice President, Drug Discovery and Development, will also present as part of a special session titled "Inhibition of AXL kinase reverses the mesenchymal phenotype in leukemia cells through the disruption of retinoic acid signaling" on October 18, 2016 at 11:20 AM CET.
About Alvocidib
Alvocidib is a potent small molecule inhibitor of cyclin-dependent kinase 9 (CDK9) in development as a combination therapy for frontline and relapsed/refractory AML. CDK9 is a protein critical to the regulation of gene expression including the MCL-1 gene and other important genes involved in cancer. Given the key role CDK9 de-regulation plays in expression of cancer-associated genes related to cell division and proliferation, CDK9 is an attractive target for the treatment of various cancers.
About TP-0903 and AXL Kinase Inhibitors
TP-0903 is a small molecule inhibitor of AXL kinase. AXL, along with other members of the TAM family of kinases, are key regulators of the mesenchymal phenotype of cancer cells. Mesenchymal cancer cells have increased invasion and migratory properties, enhanced cell survival characteristics in stressed environments, and critically, increased resistance to both targeted and traditional chemotherapies. Consequently, targeting AXL kinase with TP-0903 is an attractive way to overcome resistance to chemotherapy by targeting mesenchymal cancer cell populations.
Provectus Biopharmaceuticals Announces Poster Presentation on PV-10 at European Society of Medical Oncology 2016 Congress Now Available Online
On October 11, 2016 Provectus Biopharmaceuticals, Inc. (NYSE MKT: PVCT, www.provectusbio.com), a clinical-stage oncology and dermatology biopharmaceutical company ("Provectus" or "The Company"), reported that the poster presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016 Congress is now available online (Press release, Provectus Pharmaceuticals, OCT 11, 2016, View Source [SID:SID1234515740]).
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Titled "Intralesional Rose Bengal for Stage III and IV Melanoma," the poster (abstract 1159TIP) was presented Sunday, October 9, 2016, by Dr. Sanjiv Agarwala, and can now be viewed at: View Source
Dr. Agarwala’s presentation reviewed the current studies underway for melanoma utilizing PV-10: the phase 3 clinical trial of intralesional PV-10 as a single agent therapy for locally advanced cutaneous melanoma (study PV-10-MM-31, clinicaltrials.gov identifier NCT02288897, EudraCT no. 2016-000317-78); and the phase 1b/2, study of intralesional PV-10 in combination with immune checkpoint inhibition (study PV-10-MM-1201, NCT02557321).
Study PV-10-MM-31 is an international multicenter, open-label, randomized controlled trial (RCT) of single-agent intralesional PV-10 versus systemic chemotherapy or intralesional oncolytic viral therapy to assess treatment of locally advanced cutaneous melanoma. A total of 225 patients with Stage IIIB to IV-M1a melanoma will be randomized in a 2:1 ratio against the comparator therapy for assessment of progression free survival.
Study PV-10-MM-1201 is an international multicenter, open-label, sequential phase study of intralesional PV-10 in combination with pembrolizumab, marketed by Merck as Keytruda. Stage IV metastatic melanoma patients with at least one injectable cutaneous or subcutaneous lesion who are candidates for pembrolizumab are eligible for study participation. In the Phase 1b portion of the study, all participants receive the combination of IL PV-10 and pembrolizumab (i.e., PV-10 + standard of care). In the subsequent Phase 2 portion of the study, participants will be randomized 1:1 to receive either the combination of IL PV-10 and pembrolizumab or pembrolizumab alone for assessment of progression free survival.
Dr. Eric Wachter, Ph.D., Chief Technology Officer of Provectus, noted, "The annual ESMO (Free ESMO Whitepaper) congress has grown to be one of the largest and most important oncology meetings of the year, and we were privileged with selection for participation in the technical program. Participation in this international forum allowed us to meet face-to-face with current and prospective investigators from around the globe, thereby providing an efficient way to exchange information about our development plans, the potential impact of ongoing changes in the oncology landscape, and ways to address these impacts through refinement of protocol designs."
Dr. Wachter continued, "As we’ve reported previously, we maintain ongoing discussions with key advisors on ways to optimize our development plans, including ways that study designs can be adjusted for maximum efficiency. After a major update of our key phase 3 protocol early this year, and a smaller update at mid-year, our ESMO (Free ESMO Whitepaper) participation allowed us to test the outcome of subsequent discussions regarding further small adjustments on a broader audience in the melanoma community. We expect to implement at least several of these changes in the near future based on these discussions. In particular, allowing patients with primarily or exclusively subcutaneous melanoma (that is, melanoma below the skin surface) and those with larger tumors should not significantly affect the biological basis for our phase 3 study, but could substantially expand the fraction of patients with locally advanced disease that can participate in the study."