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ESMO Clinical Practice Guidelines for Breast Cancer Recommend the Use of Prosigna/PAM50 Assay for Determining Potential Benefit From Chemotherapy

On September 9, 2015 NanoString Technologies, Inc., (NASDAQ:NSTG) a provider of life science tools for translational research and molecular diagnostic products, reported that the PAM50 gene signature, commercialized as the Prosigna Breast Cancer Gene Signature Assay, has been added to the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Clinical Practice Guidelines (Press release, NanoString Technologies, SEP 9, 2015, View Source [SID:1234507424]). The updated guidelines recognize Prosigna’s value to provide additional prognostic and predictive information that complements the pathologic assessment predicting the benefit of adjuvant chemotherapy.

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"In cases of clinical uncertainty, the decision to use chemotherapy in early stage breast cancer patients is a challenge. Chemotherapy can have devastating short-term and long-term consequences for many patients and therefore should be used only when we have very good reasons, either related to high risk of relapse or aggressive tumor biology," said Dr. Miguel Martin, Professor of Medicine and Chair of the Spanish Group for Breast Cancer Research-GEICAM. "Prosigna is a new and robust tool to help clinicians assess tumor biology and risk of recurrence, which may help determine the appropriateness of systemic chemotherapy."

Prosigna was acknowledged as having achieved level 1B evidence for its prognostic value and is recommended for use to predict the benefit of chemotherapy. The conclusion of the guideline panel places Prosigna at parity with other established gene expression assays. The updated ESMO (Free ESMO Whitepaper) Guidelines are consistent with the recently updated St. Gallen International Breast Cancer Guidelines, which both suggest a patient’s risk of recurrence should be assessed by tumor biology and burden of disease. Additionally, the ESMO (Free ESMO Whitepaper) Guidelines indicate that the decision to use systemic adjuvant chemotherapy should be based on the intrinsic subtype, which can be efficiently determined using the CE-marked version of the Prosigna Assay. The guidelines further recommend specific systemic treatment strategies for each identified molecular subtype.

The ESMO (Free ESMO Whitepaper) Clinical Practice Guidelines are developed by an international panel of experts in accordance with ESMO (Free ESMO Whitepaper) operating procedure for assessing levels of clinical evidence. The ESMO (Free ESMO Whitepaper) Clinical Practice Guidelines for Breast Cancer are available at: View Source

"We’re pleased with the decision of the ESMO (Free ESMO Whitepaper) Clinical Practice Guideline committee to recognize the value of Prosigna for informing the use of chemotherapy in breast cancer," said Brad Gray, President and Chief Executive Officer of NanoString Technologies. "This is the third European clinical practice guideline to include Prosigna, and should support our continued success in bringing breast cancer recurrence testing to patients."

About the Prosigna Assay and the nCounter Dx Analysis System

The Prosigna Assay provides a risk category and numerical score for assessment of the risk of distant recurrence of disease at 10 years in postmenopausal women with node-negative (Stage I or II) or node-positive (Stage II or IIIA), HR+ breast cancer. Based on the PAM50 gene signature initially discovered by Charles Perou, Ph.D. and colleagues, the Prosigna Assay is an in vitro diagnostic tool that utilizes gene expression data weighted together with clinical variables to generate a risk category and numerical score to assess a patient’s risk of distant recurrence of disease. The Prosigna Assay measures gene expression levels of RNA extracted from FFPE breast tumor tissue previously diagnosed as invasive breast carcinoma.

The Prosigna Assay requires minimal hands-on time and runs on NanoString’s proprietary nCounter Dx Analysis System, which offers a reproducible and cost-effective way to profile many genes simultaneously with high sensitivity and precision.

The nCounter Dx Analysis System is a highly automated and easy-to-use platform that utilizes a novel digital barcoding chemistry to deliver high-precision multiplexed assays. The system is available in the multi-mode FLEX configuration, which is designed to meet the needs of high-complexity clinical laboratories seeking a single platform with the flexibility to run the Prosigna Assay and, when operated in the "Life Sciences" mode, process translational research experiments and multiplexed assays developed by the laboratory.

The Prosigna Breast Cancer Prognostic Gene Signature Assay Intended Use:

In the European Union, and other countries that recognize the CE mark, as well as Canada and Australia, the Prosigna Assay is indicated in female breast cancer patients who have undergone either mastectomy or breast-conserving surgery in conjunction with locoregional treatment consistent with standard of care, either as:

a. A prognostic indicator for distant recurrence-free survival at 10 years in post-menopausal women with Hormone Receptor-Positive (HR+), lymph node-negative, Stage I or II breast cancer to be treated with adjuvant endocrine therapy alone, when used in conjunction with other clinicopathological factors.

b. A prognostic indicator for distant recurrence-free survival at 10 years in post-menopausal women with Hormone Receptor-Positive (HR+), lymph node-positive (1-3 positive nodes, or 4 or more positive nodes), Stage II or IIIA breast cancer to be treated with adjuvant endocrine therapy alone, when used in conjunction with other clinicopathological factors.

Varian Helps Train Caregivers in Africa to Deliver Modern Conformal Radiotherapy Treatments for Cancer Patients

On September 9, 2015 Varian Medical Systems (NYSE: VAR) reported that it is collaborating with two leading Cape Town universities to launch Africa’s first ‘Access to Care’ program, designed to train cancer caregivers in delivering advanced conformal radiotherapy treatments (Press release, InfiMed, SEP 9, 2015, View Source [SID:1234507423]).

The three-month course, which will be delivered in conjunction with Cape Peninsula University of Technology and the University of Cape Town’s department of radiation oncology, aims to train and support radiation therapy departments to implement and maintain 3D conformal radiation therapy treatment programs at their hospitals. In many cases, the delegates’ only experience of radiotherapy will have been older cobalt-based 2D treatments.

"As radiation oncology becomes increasingly precise and cancer centers worldwide can offer ever more advanced treatments for their patients, many parts of the developing world are still significantly under-equipped with too few machines to treat their rapidly growing cancer populations," says Michael Sandhu, who heads Varian Oncology Systems’ new global market development team. "Developing regions are starting to invest in new equipment to address this capacity gap but they are often hindered by a lack of qualified staff to plan treatments and run the equipment. ‘Access to Care’ is one of the ways in which Varian, as the global leader in radiation oncology, is seeking to bridge the skills gap between well-equipped countries and developing nations."

The Access to Care program will be offering two courses a year in South Africa and each program will be attended by four teams of radiation oncologists, medical physicists and radiotherapy therapists from participating hospitals from across the African continent. The course includes three weeks of classroom-based training at Groote Schuur Hospital in Cape Town, which is equipped with a virtual linear accelerator and four workstations, followed by a 10-week remote mentorship program. A separate software lab equipped with 10 workstations is available for students to practice contouring and treatment planning – important steps in the radiotherapy process. The classroom is linked to Varian’s virtual education environment hosted in its European headquarters in Cham, Switzerland.

"The training of cancer specialists and their teams enters a new era with the Access to Care program, which is at the leading edge of training globally and will help towards better and safer care of patients with cancer," said Professor Raymond Abratt, retired head of radiation oncology at Groote Schuur Hospital and the University of Cape Town, and current chairperson of the South African Society of Clinical and Radiation Oncologists (SASCRO), at a program launch event that took place in Cape Town today. "Radiation Oncology is an important component of cancer treatment in Africa and I congratulate all those involved in realizing this exceptional facility and the associated training programs."

Access to Care also offers training programs in Vietnam and has plans to commence a similar project in Algeria. "There is some real momentum behind our ‘Access to Care’ training programs and we are excited about the chance to help provide greater access to advanced cancer treatments in developing nations," says Jose-Manuel Valentim, Varian’s director market development in the EMEIA and APAC regions.

Cancer in Africa
According to a 2013 study published in Lancet Oncology, only 23 out of 52 African countries have radiotherapy available for patients. The World Health Organization reports that by 2030 there will be some 1.6 million new cancer cases in Africa each year, resulting in 1.2 million deaths. The most common cancers in Africa are cancers of the cervix, breast, lung, liver and prostate.

Varian has installed more than 100 radiotherapy treatment systems in Africa over the last 25 years. The company recently announced major projects in Algeria, Egypt and South Africa. Varian has also installed equipment in several sub-Saharan nations including Ghana, Angola, Kenya, and Madagascar.

Immunocore’s IMCgp100 Accepted for Adaptive Pathway Pilot Programme

On September 9, 2015 Immunocore Limited, a world-leading biotechnology company developing novel T cell receptor (TCR) based biological drugs to treat cancer, viral infections and autoimmune disease, reported that its lead product, IMCgp100, has been accepted to participate in the European Medicines Agency’s (EMA) Adaptive Pathways (formerly Adaptive Licensing) pilot programme (Press release, Immunocore, SEP 9, 2015, View Source [SID1234518907]). This is part of the EMA’s strategy of providing timely access for patients to new medicines to treat serious conditions with a high unmet medical need.
Immunocore is one of a small number of companies to have been accepted into this programme and plans to seek conditional approval for IMCgp100 for the treatment of patients with metastatic uveal melanoma, a rare and fatal disease with few available treatment options.

Conversion to full approval will be subject to the successful completion of a Phase II clinical trial in uveal melanoma with long-term follow-up data.

Dr. Christina Coughlin, Chief Medical Officer at Immunocore, said: "We are delighted to have been accepted into the EMA Adaptive Pathways pilot programme, an accelerated development project that further underscores the potential benefits that IMCgp100 can bring to patients with uveal melanoma, a fatal disease that has few other treatment options. We are grateful for the collaborative regulatory feedback from the EMA on the design of our development programme as well as feedback from the European HTA agencies and patient advocacy organisations that are participating in our Adaptive Pathways pilot project." Dr. Coughlin added: "We are very pleased to be working with leading European experts in the clinical management of patients with uveal melanoma."

Five Prime Therapeutics Announces Initial Data From Ongoing Phase 1b Trial of FP-1039 in Squamous Non Small Cell Lung Cancer and Mesothelioma

On September 9, 2015 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a clinical-stage biotechnology company focused on discovering and developing novel protein therapeutics for cancer and inflammatory diseases, reported that initial data from GlaxoSmithKline’s ongoing Phase 1b clinical trial of FP-1039/GSK3052230, an FGF ligand trap, in patients with squamous non small cell lung cancer (sqNSCLC) and mesothelioma were featured today in an oral presentation by Dr. Pilar Garrido at the World Conference on Lung Cancer 2015 in Denver (Press release, Five Prime Therapeutics, SEP 9, 2015, View Source [SID:1234507435]). The presentation titled, "FP1039/GSK3052230 with chemotherapy in patients with fibroblast growth factor (FGF) pathway deregulated squamous NSCLC or MPM," included study data through August 5, 2015.

"There is a significant need for more treatment options for patients with metastatic sqNSCLC and unresectable malignant pleural mesothelioma," said Paul K. Paik, M.D, a medical oncologist and lung cancer specialist at Memorial Sloan Kettering Cancer Center and an investigator in the trial. "We are hopeful that a targeted agent like FP-1039/GSK3052230 may be able to show efficacy against these difficult to treat tumors as well as an acceptable safety profile. We look forward to the full results once the trial is completed."

The Phase 1b trial being conducted by GSK is evaluating the safety and efficacy of FP-1039/GSK3052230 weekly infusion in combination with paclitaxel plus carboplatin in previously untreated FGFR1 gene-amplified metastatic sqNSCLC (Arm A), in combination with docetaxel in FGFR1 gene-amplified metastatic sqNSCLC that has progressed after at least one line of chemotherapy (Arm B), or in combination with pemetrexed plus cisplatin in patients with untreated and unresectable malignant pleural mesothelioma (Arm C). Each arm involves a dose escalation phase, followed by an expansion phase up to 30 patients. GSK continues to enroll patients in the study.

As of August 5, 2015, 176 patients with first-line or previously-treated squamous NSCLC were tested centrally for FGFR1 gene amplification, with a positive rate of approximately 20%. 44 patients had been dosed with FP-1039/GSK3052230 at dose levels ranging from 5mg/kg to 20mg/kg in combination with chemotherapy across the three study arms. In Arm A, a maximum tolerated dose was not identified, therefore a maximum feasible dose (MFD) was determined and expansion of the arm was at 20 mg/kg IV weekly. In Arm B, dose escalation is ongoing, and in Arm C, the maximally tolerated dose was established and expansion of the arm was at 15 mg/kg IV weekly.

No dose limiting toxicities (DLTs) have been observed in sqNSCLC patients (Arms A and B), and 3 DLTs were reported in mesothelioma patients (Arm C, 20mg/kg): Grade 5 bowel perforation/ischemia, Grade 3 elevated creatinine level and Grade 3 infusion reaction. The most common adverse events across all three arms were neutropenia, anemia, constipation, diarrhea, nausea, vomiting, decreased appetite, pyrexia, fatigue, asthenia and alopecia. Infusion reactions were seen in 17%, 14%, and 37% of patients treated in Arms A, B, and C, respectively. Toxicities typically associated with small-molecule FGFR kinase inhibitors, namely hyperphosphatemia and retinal, nail, and skin changes, were not observed.

"We are encouraged by the preliminary data we’ve seen thus far from this ongoing study of FP-1039/GSK3052230, particularly in the Arm A setting," said Lewis T. "Rusty" Williams, M.D., Ph.D., president and chief executive officer of Five Prime. "Patient enrollment and dosing continues, and we hope to have full results from the study during 2016."

Five Prime licensed development and commercialization rights for FP-1039/GSK3052230 in the U.S., Europe and Canada to GSK, who funds clinical development. Five Prime retains rights outside of these regions as well as an option to co-promote FP-1039/GSK3052230 in the U.S.

About FP-1039/GSK3052230

FP-1039/GSK3052230 is a protein designed to intervene in FGF signaling. As a ligand trap, FP-1039/GSK3052230 is thought to bind to FGF ligands circulating in the extracellular space, thereby preventing these signaling proteins from reaching FGFR1 on the surface of tumor cells where they would otherwise stimulate cancer cell division and/or angiogenesis. However, FP-1039/GSK3052230 is not believed to bind to certain "hormonal" FGFs, including FGF23, which regulates phosphate levels in the blood. As a result, treatment with FP-1039/GSK3052230 treatment has not been shown to cause hyperphosphatemia, a side effect seen with small molecule inhibitors of FGF receptors, which block the activity of both cancer-associated FGFs and FGF23.

Five Prime licensed development and commercialization rights for FP-1039/GSK3052230 in the U.S., Europe and Canada to GlaxoSmithKline, who funds clinical development. The Phase 1b clinical trial is investigating treatment with FP-1039/GSK3052230 combined with standard doses of chemotherapy in patients with newly-diagnosed or recurrent FGFR1 amplified metastatic squamous non-small cell lung cancer as well as patients with malignant pleural mesothelioma, a tumor in which the FGF2 ligand is overexpressed.

U.S. FDA Grants Priority Review to Takeda’s Ixazomib for Patients with Relapsed/Refractory Multiple Myeloma

On September 9, 2015 Takeda Pharmaceutical Company Limited (TSE: 4502) reported that the U.S. Food and Drug Administration (FDA) has granted Priority Review status to the New Drug Application (NDA) for ixazomib, the first investigational oral proteasome inhibitor for the treatment of patients with relapsed and/or refractory multiple myeloma (Press release, Takeda, SEP 9, 2015, View Source [SID:1234507434]).

"We are encouraged that both the U.S. and European regulatory bodies have determined that the ixazomib applications qualify for an expedited review, underscoring the importance of new treatment options for patients with relapsed/refractory multiple myeloma," said Melody Brown, Vice President of Regulatory Affairs, Takeda. "Our ixazomib program is designed to evaluate whether sustained therapy with an oral proteasome inhibitor improves the outcomes of patients living with multiple myeloma. There is a significant unmet medical need in multiple myeloma and we look forward to working with the regulatory bodies to bring ixazomib to patients."

The FDA may grant Priority Review status, which includes expedited review, to the evaluation of applications for drugs that treat a serious condition and, if approved, would provide a significant improvement in safety or efficacy over existing treatment. Ixazomib was recently granted accelerated assessment by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA).

The NDA submission for ixazomib was primarily based on the results of the first pre-specified interim analysis of the pivotal Phase 3 trial, TOURMALINE-MM1. This study is an international, randomized, double-blind, placebo controlled clinical trial of 722 patients designed to evaluate the superiority of ixazomib plus lenalidomide and dexamethasone over placebo plus lenalidomide and dexamethasone in adult patients with relapsed and/or refractory multiple myeloma. Patients continue to be treated to progression in this trial and will be evaluated for long-term outcomes.

About Multiple Myeloma
Multiple myeloma is a cancer of the plasma cells, which are found in the bone marrow. In multiple myeloma, a group of plasma cells, or myeloma cells, becomes cancerous and multiplies, increasing the number of plasma cells to a higher than normal level. Because plasma cells circulate widely in the body, they have the potential to affect many bones in the body, possibly resulting in compression fractures, lytic bone lesions and related pain. Multiple myeloma can cause a number of serious health problems affecting the bones, immune system, kidneys and red blood cell count, with some of the more common symptoms including bone pain and fatigue, a symptom of anemia. Multiple myeloma is a rare form of cancer, with approximately 20,000 new cases in the U.S. and 114,000 new cases globally per year.

About Ixazomib
Ixazomib is an investigational oral proteasome inhibitor which is being studied in multiple myeloma, systemic light-chain (AL) amyloidosis, and other malignancies. Ixazomib was granted orphan drug designation in multiple myeloma in both the U.S. and Europe in 2011 and for AL amyloidosis in both the U.S. and Europe in 2012. Ixazomib received Breakthrough Therapy status by the U.S. FDA for relapsed or refractory AL amyloidosis in 2014. It is also the first oral proteasome inhibitor to enter Phase 3 clinical trials.

Ixazomib’s clinical development program further reinforces Takeda’s ongoing commitment to developing innovative therapies for people living with multiple myeloma worldwide and the healthcare professionals who treat them. Five global Phase 3 trials are ongoing:

TOURMALINE-MM1, investigating ixazomib vs. placebo, in combination with lenalidomide and dexamethasone in relapsed and/or refractory multiple myeloma

TOURMALINE-MM2, investigating ixazomib vs. placebo, in combination with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma

TOURMALINE-MM3, investigating ixazomib vs. placebo as maintenance therapy in patients with newly diagnosed multiple myeloma following induction therapy and autologous stem cell transplant (ASCT)

TOURMALINE-MM4, investigating ixazomib vs. placebo as maintenance therapy in patients with newly diagnosed multiple myeloma who have not undergone ASCT

TOURMALINE-AL1, investigating ixazomib plus dexamethasone vs. physician choice of selected regimens in patients with relapsed or refractory AL amyloidosis

For additional information on the ongoing Phase 3 studies please visit www.clinicaltrials.gov.