On November 5, 2018 Provectus (OTCQB: PVCT) reported that the Company was granted orphan drug designation (ODD) by the U.S. Food and Drug Administration (FDA) for small molecule oncolytic immunotherapy PV-10 for the treatment of neuroblastoma, a non-central nervous system (CNS) pediatric solid tumor (Press release, Provectus Biopharmaceuticals, NOV 5, 2018, View Source [SID1234530736]). Intratumoral injection of PV-10 can yield immunogenic cell death (ICD) in solid tumor cancers and stimulate tumor-specific reactivity in circulating T cells.1-4

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Neuroblastoma forms from immature nerve cells and usually begins in the adrenal glands. It may also begin in the abdomen, chest, or near the spine. Neuroblastoma most often occurs in children younger than 5 years of age, and presents when the tumor grows and causes symptoms. According to the National Cancer Institute SEER Cancer Statistics Review 1975-2015, the 5-year survival among children 0 to 19 years of age is 75.2%.5

Initial non-clinical testing of PV-10 in treatment-refractory neuroblastoma has closely paralleled previous non-clinical and clinical study of PV-10 for murine and human adult solid tumors, at both the tumor (selective destruction of injected tumors) and cellular (ICD) levels.6 Non-clinical investigation by member institutions of the Pediatric Oncology Experimental Therapeutics Investigators’ Consortium (POETIC) has confirmed that ICD also occurs in neuroblastoma.

The FDA grants ODD status to medicines intended for the treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the US. ODD status qualifies companies for benefits that include seven years of market exclusivity following marketing approval, tax credits on U.S. clinical trials, eligibility for orphan drug grants, and waiver of certain administrative fees.

ODD status previously was granted to PV-10 for the treatments of metastatic melanoma in 2007 and hepatocellular carcinoma (HCC) in 2013.

About Neuroblastoma

If detected at an early stage, surgery is the definitive treatment. Once neuroblastoma has recurred or spread from the primary site, therapeutic options are limited principally to chemotherapy or clinical trial.7 A recent review of emerging treatment options for neuroblastoma noted that "less than 50% of patients with high-risk neuroblastoma will survive long-term with current therapies, and survivors are at risk for serious treatment-related late toxicities."8

Therapeutic options include high-dose systemic chemotherapy with alkylating agents, radiation therapy, experimental treatments like regional therapy, or immunotherapy. Unlike many adult solid tumor types, pediatric solid tumors have largely proven unresponsive to immune checkpoint inhibitors such as anti-PD-1 antibodies. A recent Phase 2 study of pembrolizumab in pediatric solid tumors showed that less than 20% of patients tested were candidates for anti-PD-1 therapy based on low expression of the PD-L1 biomarker, and no candidates achieved an objective response.9

About PV-10

Provectus’ lead investigational oncology drug, PV-10, the first small molecule oncolytic immunotherapy, can induce immunogenic cell death. PV-10 is undergoing clinical study for adult solid tumor cancers, like melanoma and cancers of the liver, and preclinical study for pediatric cancers.

About the Pediatric Oncology Experimental Therapeutics Investigators’ Consortium

The Pediatric Oncology Experimental Therapeutics Investigators’ Consortium (POETIC) was founded in February 2003 by Dr. Tanya Trippett at Memorial Sloan Kettering Cancer Center and Dr. Lia Gore at the University of Colorado Cancer Center. POETIC is composed of ten large academic medical centers in North America with a major emphasis on comprehensive cancer care and research that provide the collaborative and research strength needed to complete intensive phase I and II studies. Each of the institutions is uniquely suited to complete early studies in the pediatric and adolescent populations. POETIC’s assets include membership in NCI-designated Comprehensive Cancer Centers, on-site NIH-funded pediatric and/or general clinical translational research centers (CTRCs/CTSAs), and active collaborations with developmental therapeutics programs for adults at a majority of its member institutions. The availability of strong basic science and translational research programs at the institutions allows focus on the development and evaluation of new therapeutic strategies for patients with cancer and related disorders. POETIC’s pediatric oncology studies focus on the biologic basis for anti-cancer therapy, and in particular, attempt to explore and evaluate novel agents and/or combinations of therapies early in clinical development as well as new approaches to targeted delivery. For additional information about POETIC, please visit the Consortium’s website at www.poeticphase1.org.

On November 5, 2019 Cotinga Pharmaceuticals Inc. (TSX Venture: COT; OTCQB: COTQF) ("Cotinga" or the "Company"), a clinical-stage pharmaceutical company advancing a pipeline of targeted therapies for the treatment of cancer, reported that it has entered into a research collaboration with St. Vincent’s University Hospital in Dublin, Ireland to evaluate COTI-2 in combination with eribulin in patients with triple negative metastatic breast cancer (Press release, Cotinga, NOV 5, 2018, View Source [SID1234533149]).

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"Cotinga is committed to the development of therapies for a wide range of cancers, and our collaboration with St. Vincent’s University Hospital represents an important step towards realizing the full potential of our lead compound, COTI-2," said Dr. Richard Ho, M.D., Ph.D., Chief Scientific Officer. "Throughout this year we presented preclinical and early clinical results that support COTI-2 as a possible combination therapy, and this partnership with St. Vincent’s will allow us to further explore how COTI-2 may work alongside the standard of care in cancers with severe unmet medical need."

The Phase 1 study will aim to evaluate COTI-2 in combination with eribulin in the second or subsequent line therapy of patients with triple negative metastatic breast cancer. The primary objectives of the study will be to determine the optimal tolerated dose of COTI-2 that can be added to standard dose eribulin in the second or subsequent line treatment of metastatic breast cancer, and to assess the safety and tolerability of COTI-2 when administered with eribulin.

"Triple-negative metastatic breast cancer is a serious and difficult-to-treat disease that tends to be more aggressive than other types of breast cancer," said Professor John Crown, M.D., M.B.A., consultant medical oncologist at St. Vincent’s University Hospital. "Our research demonstrates that the p53 gene is mutated in approximately 80% of triple-negative tumors, and suggests that mutant p53 has potential as a therapeutic target. We are encouraged by early data from COTI-2, which targets mutant p53, and having seen synergy in our own preclinical testing of COTI-2 and eribulin, we look forward to evaluating the compound in combination with standard of care for patients with triple negative metastatic breast cancer."

On November 5, 2018 Alpine Immune Sciences, Inc. (NASDAQ:ALPN), a leading immunotherapy company focused on developing innovative treatments for cancer, autoimmune/inflammatory, and other diseases, reported the company will participate in two upcoming investor conferences in November (Press release, Alpine Immune Sciences, NOV 5, 2018, View Source [SID1234530719]).

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The company will present at the Stifel 2018 Healthcare Conference on Tuesday, November 13, 2018 at 2:45 pm Eastern Time in New York.

Additionally, Mitchell H. Gold, M.D., Executive Chairman and Chief Executive Officer of Alpine, will participate in an analyst-led fireside chat at the 30th Annual Piper Jaffray Healthcare Conference on Wednesday, November 28, 2018 at 1:30 pm Eastern Time in New York.

A live webcast of each presentation will be available online in the investor relations section of the company’s website at View Source A replay of the presentations will be available on the company website for 90 days following the webcast.

On November 5, 2018 Seattle Genetics, Inc. (Nasdaq:SGEN) reported that it has submitted a supplemental Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) based on data from the phase 3 ECHELON-2 trial evaluating ADCETRIS (brentuximab vedotin) in combination with chemotherapy for the frontline treatment of patients with CD30-expressing peripheral T-cell lymphoma (PTCL) (Press release, Seattle Genetics, NOV 5, 2018, View Source [SID1234530737]). The positive topline results of the phase 3 ECHELON-2 clinical trial were announced in October 2018 and full data will be presented at the upcoming American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, December 1-4, 2018 in San Diego, Calif. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, which is expressed on the surface of several types of PTCL. ADCETRIS is currently not approved for the frontline treatment of PTCL.

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"CD30 is expressed in several subtypes of peripheral T-cell lymphoma, an aggressive type of non-Hodgkin lymphoma, and the current standard of care for frontline treatment consisting of a multi-agent chemotherapy regimen called CHOP has not changed in several decades," said Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. "Results from the ECHELON-2 trial demonstrated a statistically significant and clinically meaningful improvement in progression-free survival and importantly, overall survival, in patients with previously untreated CD30-expressing PTCL who were treated with ADCETRIS in combination with CHP chemotherapy over standard of care CHOP chemotherapy. We believe these superior results over standard of care represent a significant advance for patients with CD30-expressing PTCL and for the medical community, and we look forward to working with the FDA during the review process of this application to bring this potential new treatment regimen to patients as quickly as possible."

The phase 3 ECHELON-2 clinical trial evaluated the combination of ADCETRIS plus CHP (cyclophosphamide, doxorubicin, prednisone) compared to a recognized standard of care chemotherapy regimen, CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), in previously untreated CD30-expressing PTCL. The ECHELON-2 study met its primary endpoint demonstrating a statistically significant improvement in progression-free survival (PFS) as assessed by an Independent Review Facility (IRF; hazard ratio=0.71; p-value=0.0110). The ADCETRIS plus CHP arm also demonstrated superior overall survival (OS), a key secondary endpoint, compared to CHOP (hazard ratio=0.66; p-value=0.0244). All other key secondary endpoints, including PFS in patients with systemic anaplastic large cell lymphoma (sALCL), complete remission rate and objective response rate were statistically significant in favor of the ADCETRIS plus CHP arm. The safety profile of ADCETRIS plus CHP in the ECHELON-2 trial was comparable to CHOP and consistent with the established safety profile of ADCETRIS in combination with chemotherapy. Full data will be presented at the ASH (Free ASH Whitepaper) Annual Meeting in the following session:

Oral Session: Hodgkin Lymphoma and T/NK Cell Lymphoma—Clinical Studies: T-Cell Lymphoma: Chemotherapy and Targeted Approaches (Abstract #997)
Date/Location: Monday, December 3, 2018 at 6:15 p.m. PT, San Diego Convention Center, Room 6F
Presenter: Steven Horwitz, M.D., Department of Medicine, Lymphoma Service, Memorial Sloan-Kettering Cancer Center, New York
ECHELON-2 Phase 3 Clinical Trial Design

The randomized, double-blind, placebo-controlled phase 3 trial is investigating ADCETRIS plus CHP (cyclophosphamide, doxorubicin, prednisone) versus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) as frontline therapy in patients with CD30-expressing peripheral T-cell lymphoma, also known as mature T-cell lymphoma. The primary endpoint is progression-free survival (PFS) per Independent Review Facility assessment, with events defined as progression, death, or receipt of chemotherapy for residual or progressive disease. Secondary endpoints include PFS in patients with systemic anaplastic large cell lymphoma (sALCL), complete remission rate, overall survival and objective response rate, in addition to safety. The multi-center trial was conducted at sites across North America, Europe and Asia and was designed to enroll 450 patients, approximately 75 percent of whom were to be diagnosed with sALCL. The ECHELON-2 trial is being conducted under a Special Protocol Assessment (SPA) agreement from the U.S. Food and Drug Administration (FDA) and the trial also received European Medicines Agency (EMA) scientific advice.

Please see Important Safety Information at the end of this press release.

About T-Cell Lymphomas

Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma. There are more than 60 subtypes of non-Hodgkin lymphomas which are broadly divided into two major groups: B-cell lymphomas, which develop from abnormal B-lymphocytes, and T-cell lymphomas, which develop from abnormal T-lymphocytes. There are many different forms of T-cell lymphomas, some of which are extremely rare. T-cell lymphomas can be aggressive (fast-growing) or indolent (slow-growing). PTCL accounts for approximately 10 percent of non-Hodgkin lymphoma cases in the U.S. and Europe and may be as high as 24 percent in parts of Asia.

About ADCETRIS (brentuximab vedotin)

ADCETRIS is being evaluated broadly in more than 70 clinical trials in CD30-expressing lymphomas. These include the recently completed phase 3 ECHELON-2 trial in frontline peripheral T-cell lymphomas (also known as mature T-cell lymphoma), the completed phase 3 ECHELON-1 trial in previously untreated Hodgkin lymphoma, the completed phase 3 ALCANZA trial in cutaneous T-cell lymphoma, and the ongoing CHECKMATE 812 trial of ADCETRIS in combination with Opdivo (nivolumab) for relapsed/refractory Hodgkin lymphoma.

ADCETRIS is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’ proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells.

ADCETRIS injection for intravenous infusion has received FDA approval for five indications in adult patients with: (1) previously untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with chemotherapy, (2) cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation, (3) cHL after failure of auto-HSCT or failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (4) sALCL after failure of at least one prior multi-agent chemotherapy regimen, and (5) primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.

Health Canada granted ADCETRIS approval with conditions for relapsed or refractory Hodgkin lymphoma and sALCL in 2013, and non-conditional approval for post-autologous stem cell transplantation (ASCT) consolidation treatment of Hodgkin lymphoma patients at increased risk of relapse or progression.

ADCETRIS received conditional marketing authorization from the European Commission in October 2012. The approved indications in Europe are: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following ASCT, or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, (2) the treatment of adult patients with relapsed or refractory sALCL, (3) for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT, and (4) for the treatment of adult patients with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy.

ADCETRIS has received marketing authorization by regulatory authorities in 72 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See select important safety information, including Boxed Warning, below.

Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.

On November 5, 2018 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company focused on the development of precision medicines for oncology, reported the initiation of its global, multi-center, registration-directed trial of tipifarnib in HRAS mutant head and neck squamous cell carcinomas (HNSCC) (Press release, Kura Oncology, NOV 5, 2018, View Source [SID1234530720]).

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"We are excited to announce that our first registration-directed trial is now underway," said Antonio Gualberto, M.D., Ph.D., Head of Development and Chief Medical Officer of Kura Oncology. "Prior to our experience, tipifarnib was studied in more than 5,000 patients and although it demonstrated compelling anti-cancer activity in some cases, no molecular target was identified that could explain such activity. This registration-directed trial implements the many learnings from our clinical experience in patients with HNSCC. We believe we can now identify those patients most likely to receive clinical benefit from tipifarnib. If successful, we believe this registration-directed trial could bring a much-needed treatment option to patients with HRAS mutant HNSCC."

About the Registration-Directed Trial

Kura’s registration-directed clinical trial is a global, multi-center study of tipifarnib in HRAS mutant HNSCC. The open-label trial has two cohorts: AIM-HN, a treatment cohort, and SEQ-HN, a non-interventional screening and outcomes cohort.

AIM-HN is designed to enroll at least 59 patients with HRAS mutant HNSCC who have received prior platinum-based therapy, and is expected to take approximately two years to fully enroll. Based on observations from Kura’s Phase 2 trial, patients in AIM-HN must have a tumor HRAS mutant allele frequency of at least 20%. Enrolled patients will receive a starting dose of 600 mg of oral tipifarnib, twice daily, on days 1-7 and 15-21 of 28-day treatment cycles. The trial’s primary endpoint is objective response rate (ORR), as determined by independent radiological review. Secondary outcome measures will include overall survival, duration of response, progression free survival and time to response.

AIM-HN has approximately 80% power to detect a difference between a null hypothesis of 15%, which is the point estimate of the ORR of second-line therapy for recurrent and metastatic disease, and 30%, an ORR considered of interest. Based on feedback from the U.S. Food and Drug Administration (FDA), Kura believes that AIM-HN, if positive, may be adequate to support a new drug application (NDA) seeking accelerated approval.

SEQ-HN is an observational cohort and is designed as a case-control study, matching patients with recurrent or metastatic HNSCC with HRAS mutations against those who are HRAS wild type using factors such as age, line of therapy and type of treatment. SEQ-HN is expected to provide a better understanding of the natural history of patients with HRAS mutations while contributing to identify patients for potential enrollment into AIM-HN. HNSCC patients in whom HRAS mutations are identified and who meet eligibility criteria will be offered participation in AIM-HN. HNSCC patients in whom HRAS mutations are not identified may enroll into SEQ-HN.

Additional information about the trial can be found at clinicaltrials.gov using the identifier NCT03719690.

About Tipifarnib

Kura Oncology’s lead candidate, tipifarnib, is an inhibitor of 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. Leveraging advances in next-generation sequencing as well as emerging information about cancer genetics and tumor biology, the Company is seeking to identify those patients most likely to benefit from tipifarnib. In addition to its development program in solid tumors with HRAS mutations, Kura has identified the CXCL12 pathway and bone marrow homing of myeloid cells as potential biomarkers of activity for tipifarnib in certain hematologic malignancies. The Company plans to present preliminary data from the angioimmunoblastic T-cell lymphoma (AITL) and CXCL12+ expansion cohorts in a Phase 2 trial of tipifarnib in peripheral T-cell lymphomas (PTCL) at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2018.