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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.

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]).

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."

Nymox Reports Successful New Phase 3 Long-Term Fexapotide Repeat Injection BPH Trial Results: Lasting Symptomatic Improvement Up To 6 Years After Single Repeated Treatment

On October 11, 2016 Nymox Pharmaceutical Corporation (NASDAQ:NYMX) reported successful new study results from the long-term repeated injection group from the U.S. Phase 3 trials for fexapotide, the Company’s lead compound in late stage development for enlarged prostate (BPH) and for localized prostate cancer (Press release, Nymox, OCT 11, 2016, View Source;fvtc=4&fvtv=6907 [SID:SID1234515739]). The aim of the study was to determine the safety and clinical benefit fexapotide can provide to men who were given a second injection of fexapotide for their prostate enlargement (BPH). In the new study long-term outcomes were determined in 344 patients who were given a single repeat fexapotide treatment after initial blinded treatment with fexapotide or placebo. Patients were followed for 2 to 6.5 years (mean 4.2 years) after initial treatment. All treatment failures were included in the analysis. Results have now shown that there was long-term statistically significant symptomatic improvement (mean improvement of 6.5 points in the AUA BPH Symptom Score) compared to Phase 3 patients who received placebo alone (p<.001). Repeat injection was found to be safe with no significant drug related toxicities or side effects found in the study.

"These prospective long-term study results in reinjected patients clearly demonstrate that fexapotide leads to clinically meaningful long-term symptomatic improvements in BPH patients with minimal treatment, and without the worrisome and bothersome toxicities of conventional BPH treatments such as retrograde ejaculation, and increased cancer risk," said Dr. Paul Averback MD, CEO of Nymox. "Our earlier reported Phase 3 studies have shown that fexapotide reduces the long-term need for surgery by up to 82-95% compared to approved conventional BPH treatments. Data indicates that fexapotide shows significant efficacy against prostate cancer as a therapeutic, and in addition has been shown in Phase 3 to reduce the risk of prostate cancer when fexapotide is used to treat BPH. This is in comparison to some conventional BPH treatments in routine clinical use today which on the other hand increase prostate cancer risk, and which have these many other well known undesirable side effects," he said.

Nymox’s lead drug fexapotide has been in development for over a decade and has been tested by expert clinical trial investigative teams in over 70 distinguished clinical trial centers throughout the US, and has been found after 7 years of prospective placebo controlled double blind studies of treatment of 995 U.S. men with prostate enlargement to not only show clinically meaningful and durable relief of BPH symptoms, but also to show a major reduction in the incidence of prostate cancer, compared to placebo and compared to the known and expected normal incidence of the disease. The same clinical program conducted at the same highly regarded treatment centers under rigorous trial scrutiny and performed strictly at arms-length by top teams of clinical investigators across the country, has also shown in a long-term blinded placebo crossover group study an 82-95% reduction in the number of these patients who required surgery after they received crossover fexapotide in the trial, as compared to patients who did not receive fexapotide but instead received crossover conventional approved BPH treatments (p<.0001). The aim of the crossover study was to determine the clinical benefit fexapotide can provide to men who initially were double blind randomized to and received placebo, remained blinded as to their placebo treatment, and who subsequently required additional medical and/or surgical treatment. In that study long-term outcomes were determined in 391 patients who were given double blind placebo injections, followed by crossover to other treatments at the patients’ discretion. The numbers of blinded placebo patients who subsequently received surgical treatment during the next 2-3 years for their BPH symptoms were then prospectively analyzed.

For the earlier fexapotide Phase 3 long-term cancer incidence analysis, the men in the study received fexapotide or placebo for the treatment of their prostate enlargement (BPH) symptoms. All men were thoroughly evaluated at expert urological testing investigational centers to exclude any prostate cancer prior to qualifying for enrollment in the studies. The participants were followed for up to 7 years (median of 5 years) after treatment. The study analyzed all cases of prostate cancer that were subsequently diagnosed. The expected rate of new prostate cancer in the U.S. general male population in this age group is in the 5-20% range after 7 years. In the BPH population in published large trials of drugs for the prevention of prostate cancer, the incidence of new prostate cancer cases after 4-7 years has been reported in major studies to be 20-25%. The data analysis from the Nymox fexapotide study showed a statistically significant and very low incidence of 1.3% for prostate cancer in this comparable fexapotide treated BPH population. By comparison, for example in a population of patients with erectile dysfunction treated with PDE5 inhibitor drugs after 4 years the rate of subsequent prostate cancer was 19.5% (and 22.7% in controls) as recently reported in a large U.S. study published in the Journal of Urology (Volume 196; 3, 2016). The quoted study was in a population of middle aged and elderly men without prostate cancer, similar to the Nymox study population.

Nymox has completed and fully financed the execution of seven Phase 3 U.S. BPH clinical protocols, including 2 prospective randomized multicenter single injection double blind clinical trials; 2 U.S. repeat injection clinical trials; and 3 U.S. blinded long-term clinical trial extension studies. In addition, a number of Phase 3 safety and clinical pharmacology studies and analyses have been completed. The Company expects to file for approvals in the next 1-2 quarters. The Company also expects to report further analyses and results when available in the near future. The Company will publish the findings of the fexapotide clinical trials in peer review medical journals as well as in presentations at medical and urological meetings

Kite Pharma to Host Investor Day on October 18, 2016 Spotlighting an Industry-Leading CAR/TCR Pipeline, Next Generation Research and Development, and KTE-C19 Launch Readiness

On October 11,2016 Kite Pharma, Inc. (Nasdaq:KITE) reported that it will hold an Investor Day on October 18, 2016 in New York where the company will share updates on its advancing pipeline of chimeric antigen receptor (CAR) and T cell receptor (TCR) product candidates, next generation research and development programs, and KTE-C19 launch readiness. The event and live webcast will begin at 12:00pm Eastern Time (Press release, Kite Pharma, OCT 11, 2016, View Source [SID:SID1234515737]). The live audio webcast can be accessed through the Events and Presentations section under the Investors tab of Kite’s website at www.kitepharma.com. Following the live audio webcast, a replay will be available on Kite’s website for approximately 30 days.

About KTE-C19

Kite Pharma’s lead product candidate, KTE-C19, is an investigational therapy in which a patient’s T cells are engineered to express a CAR to target the antigen CD19, a protein expressed on the cell surface of B-cell lymphomas and leukemias, and redirect the T cells to kill cancer cells. KTE-C19 has been granted Breakthrough Therapy Designation status for diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), and primary mediastinal B-cell lymphoma (PMBCL) by the U.S. Food and Drug Administration and Priority Medicines (PRIME) regulatory support for DLBCL in the EU.