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."

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.

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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On October 10, 2016 Panther Biotechnology, Inc. reported that a request for a Pre-IND (Investigational New Drug) meeting with the Division of Oncology Products 1 (DOP1) of the Center for Drug Evaluation and Research (CDER) of the U.S. Food and Drug Administration ("FDA") has been submitted (Press release, Panther Biotechnology, OCT 10, 2016, View Source [SID1234517403]). The purpose of the requested meeting is to obtain FDA’s input regarding Panther’s plans for the development of TRF-DOX, Panther’s novel transferrin-doxorubicin conjugate for the treatment of platinum-resistant ovarian cancer. In preparation for the meeting, Panther is preparing a Pre-IND Package to be submitted to FDA that describes the information Panther intends on submitting in the TRF-DOX IND planned for submission in 2017. The IND is the regulatory vehicle that will allow for the initiation of clinical trials with TRF-DOX for the treatment of ovarian cancer.

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FDA will specifically review Panther’s manufacturing, preclinical pharmacology and toxicology, and clinical plans for TRF-DOX and provide specific feedback to Panther prior to the meeting.

TRF-DOX binds to transferrin receptors on tumor cells, inhibits cancer cell proliferation and causes cell death. TRF-DOX has been shown to exhibit increased cytotoxicity relative to unconjugated doxorubicin toward a variety of cancer cell lines and reduced cytotoxicity to normal cells. In addition to improvements in cytotoxicity and selectivity, TRF-DOX exhibits cytotoxic effects in many multidrug-resistant cells in vitro. Tumor targeting of doxorubicin to transferrin receptors on the cell membranes of tumor cells is intended to improve the therapeutic index of doxorubicin and to reduce the development of doxorubicin resistance. Panther is proposing to conduct an open label, multiple ascending dose study to investigate the safety, pharmacokinetics and preliminary efficacy of TRF-DOX in patients with platinum-resistant ovarian cancer.

On October 10, 2016 Galena Biopharma, Inc. (NASDAQ:GALE), a biopharmaceutical company committed to the development and commercialization of hematology and oncology therapeutics that address unmet medical needs, reported that it has presented interim safety data from the Company’s NeuVax (nelipepimut-S) Phase 2b combination study with trastuzumab at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016 Congress in Copenhagen, Denmark (Press release, Galena Biopharma, OCT 10, 2016, View Source [SID:SID1234515719]). The clinical trial is a randomized, multicenter, investigator-sponsored, 300 patient Phase 2b study. It is currently enrolling HER2 1+ and 2+ node positive, and high-risk node negative patients to study NeuVax in combination with trastuzumab to prevent breast cancer recurrence.

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Poster #1069P, entitled "Interim safety analysis of a phase II trial combining trastuzumab and NeuVax, a HER2-targeted peptide vaccine, to prevent breast cancer recurrence in HER2 low expression," demonstrated that this novel combination of trastuzumab and NeuVax in HER2 low-expressing (LE) patients is well-tolerated and the cardiac effects of trastuzumab are not impacted by the addition of NeuVax.

In March 2016, the 150th patient was randomized into the trial, triggering this pre-specified safety analysis (Vaccine Group (VG) n=81, Control Group (CG) n=69). There were no significant differences in treatment factors, but a significant difference in node positivity appreciated between the groups. The sponsor expects this randomization imbalance to equalize over the duration of the study. Cardiac ejection fraction (EF) was assessed at baseline and serially throughout treatment. The majority of toxicities were Grade 1 and 2, and there was no difference between treatment arms. There was no difference in EF over time (baseline (T0) to 6mo (T6)) between VG v CG (T0: 61.4+0.6%, T6: 60.5+0.9% v T0: 61.6+0.7%, T6: 60.7+1.0%, p=0.9). There was one CG patient who experienced a grade 3 cardiac adverse event, but their EF returned to baseline after discontinuation of trastuzumab.

"This pre-specified, interim safety analysis is crucial to this trial to ensure that the combination of NeuVax and trastuzumab is well-tolerated in patients, and importantly that it does not increase the cardio-toxicity effects known to be associated with trastuzumab," said Bijan Nejadnik, M.D., Executive Vice President and Chief Medical Officer. "There is a growing consensus that combination therapies may yield the greatest clinical benefit, and this Phase 2b trial remains ongoing with enrollment expected to complete by the end of this year. As a result, we expect to report our first interim efficacy and immunologic outcomes after 12 months of follow-up, currently expected at the end of 2017. We are grateful to Dr. George Peoples and his team who continue this groundbreaking work."

Disease-free, HLA-A2+, A3+, A24+, or A26+, HER2 LE breast cancer patients at high risk for recurrence were enrolled after standard of care treatment and randomized to vaccine group (VG) receiving trastuzumab and NeuVax or control group (CG) receiving trastuzumab and GM-CSF only. Trastuzumab dosing was 8mg/kg loading, then 6mg/kg every 3 weeks. Patients received 6 total inoculations of NeuVax or GM-CSF, one every 3 weeks starting with the third trastuzumab infusion, followed by four booster inoculations administered every 6 months. Demographic and safety data were collected and analyzed with appropriate statistical tests.

The poster presentation from the conference will be available on Galena’s website here.
Abstract #3981 can be found on the conference website here.

About NeuVax (nelipepimut-S)

NeuVax (nelipepimut-S) is a first-in-class, HER2-directed cancer immunotherapy under evaluation to prevent breast cancer recurrence after standard of care treatment in the adjuvant setting. It is the immunodominant peptide derived from the extracellular domain of the HER2 protein, a well-established target for therapeutic intervention in breast carcinoma. The nelipepimut-S sequence stimulates specific CD8+ cytotoxic T lymphocytes (CTLs) following binding to specific HLA molecules on antigen presenting cells (APC). These activated specific CTLs recognize, neutralize and destroy, through cell lysis, HER2 expressing cancer cells, including occult cancer cells and micrometastatic foci. The nelipepimut-S immune response can also generate CTLs to other immunogenic peptides through inter- and intra-antigenic epitope spreading. In clinical studies, NeuVax is combined with recombinant granulocyte macrophage-colony stimulating factor (GM-CSF).

NeuVax is currently in two breast cancer studies in combination with trastuzumab (Herceptin; Genentech/Roche): a Phase 2b trial in node positive and triple negative HER2 IHC 1+/2+ (clinicaltrials.gov identifier: NCT01570036); and, a Phase 2 trial in high risk, node positive or negative HER2 IHC 3+ patients (clinicaltrials.gov identifier: NCT02297698). Phase 2 clinical trials with NeuVax are also planned in patients with ductal carcinoma in situ (DCIS), and in patients with gastric cancer.

About HER2 1+/2+ Breast Cancer

According to the National Cancer Institute, over 230,000 women in the U.S. are diagnosed with breast cancer annually. Of these women, only about 25% are HER2 positive (IHC 3+). NeuVax targets approximately 50%-60% of these women who are HER2 low to intermediate (IHC 1+/2+ or FISH < 2.0) and achieve remission with current standard of care, but have no available HER2-targeted adjuvant treatment options to maintain their disease-free status.