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]).

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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.

On September 9, 2015 Aduro Biotech, Inc. (Nasdaq:ADRO) reported that it has entered into a clinical trial agreement with Incyte Corporation (Nasdaq:INCY) to evaluate the safety, tolerability and preliminary efficacy of Aduro’s lead LADD immunotherapy, CRS-207, in combination with Incyte’s oral indoleamine dioxygenase 1 (IDO1) inhibitor, epacadostat (INCB24360), in patients with ovarian cancer (Press release, Aduro BioTech, SEP 9, 2015, View Source;p=RssLanding&cat=news&id=2086398 [SID:1234507459]).

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The combination of both investigational immunotherapeutic agents, which have different but complementary mechanisms directed at enhancing the body’s own immune defenses, may provide unique synergies in fighting cancer. Incyte’s epacadostat has been shown in vitro and in preclinical tumor models to enhance activities of multiple types of immune cells by reducing the immune suppression characteristic of the tumor microenvironment. Aduro’s CRS-207 has been shown to stimulate immune cell activity, with particular targeting mechanisms that seek and attack tumor cells that express mesothelin like those found in ovarian cancer.

"There’s a growing body of evidence and enthusiasm in the field of oncology to combine therapeutic agents with different mechanisms that may result in very powerful approaches to treating tough cancers," said Stephen T. Isaacs, chairman, president and chief executive officer of Aduro. "Incyte is a leader in the field of cancer immunotherapy and we’re pleased to join forces with them to study a novel approach to treating ovarian cancer."

Rich Levy, M.D., chief drug development officer of Incyte added, "This clinical trial collaboration with Aduro is an important opportunity to further investigate the therapeutic value of epacadostat in advanced ovarian cancer. Research partnerships like this one help us deliver on our goal of advancing innovative science to improve patients’ lives."

The Phase 1/2 trial, which is being funded equally between the two companies, is designed to test combinations of CRS-207 with two dose levels of epacadostat in dose escalation and then will expand to a Phase 2 evaluating the combination at the optimal dose level compared to CRS-207 alone based on safety and tumor biomarkers. The study plans to enroll up to 40 patients in Phase 1 and up to 86 patients in Phase 2 with platinum-resistant ovarian, fallopian or peritoneal cancers. The trial is expected to begin enrolling patients in early 2016.

Under the terms of the collaboration, Aduro and Incyte will collaborate on a non-exclusive basis to evaluate the combination. Aduro will be responsible for conducting the study and the results will be used to determine whether further clinical development of this combination is warranted.

About Epacadostat

Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive enzyme that has been shown to induce regulatory T cell generation and activation, and allow tumors to escape immune surveillance. Epacadostat is an orally bioavailable small molecule inhibitor of IDO1 that has nanomolar potency in both biochemical and cellular assays and has demonstrated potent activity in enhancing T lymphocyte, dendritic cell and natural killer cell responses in vitro, with a high degree of selectivity. Epacadostat has shown proof-of-concept clinical data in patients with unresectable or metastatic melanoma in combination with the CTLA-4 inhibitor ipilimumab, and is currently in four proof-of-concept clinical trials with PD-1 and PD-L1 immune checkpoint inhibitors in a variety of cancer types.

About CRS-207

CRS-207 is one of a family of product candidates based on Aduro’s live-attenuated, double-deleted (LADD) Listeria monocytogenes immuno-oncology platform that are designed to induce potent innate and adaptive immune responses. CRS-207 has been engineered to express the tumor-associated antigen mesothelin, which is over-expressed in many cancers including mesothelioma and pancreatic, non-small cell lung, ovarian and gastric cancers.

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.

On September 9, 2015 Myriad Genetics, Inc. (NASDAQ:MYGN) reported two posters on its myPlan Lung Cancer prognostic test at the International Association for the Study of Lung Cancer (IASLC) 16TH World Conference on Lung Cancer being held in Denver, Colo (Press release, Myriad Genetics, SEP 9, 2015, View Source [SID:1234507430]).

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The first study showed that the myPlan Lung Cancer test identified more patients with Stage IB lung cancer who are at risk for disease progression than were identified with National Comprehensive Cancer Network (NCCN) high-risk factors alone. The second study highlighted the successful analytical validation of the myPlan test, which demonstrated very high analytical precision.

"We use relatively crude categories of stage that were developed over 60 years ago to decide when to give chemotherapy. There is no routine assessment of the biology of the tumor, which we now know is a primary determinant of the risk of recurrence and cancer death," said Daniel Oh, M.D., Keck School of Medicine, University of Southern California. "Several validation studies from premiere cancer centers in this country have been presented and published that demonstrate the efficacy of myPlan Lung Cancer. I believe that the test is an important step forward in improving outcomes of lung cancer patients and allows a more rational approach to tailoring the treatment of our patients."

Below are details of the myPlan Lung Cancer studies that were highlighted at #WCLC2015.

Poster Presentation: P3.04-074.
Title: Prognostic Multigene Molecular Assay Might Improve Identification of Pathologic Stage IB Lung Adenocarcinoma Patients at Risk for Recurrence.
Date: Wednesday, Sept. 9, 2015: 9:45 to 10:45 a.m. and 3:45 to 4:45 p.m.

This study compared Stage IB patient risk as assessed by the myPlan Lung Cancer prognostic test score, which is a combination of cell cycle progression score and pathologic stage, versus NCCN high-risk features. Of the 279 Stage IB patients evaluated, 183 (65.6 percent) were designated high risk by the myPlan Lung Cancer test. Of these high-risk patients, less than 50 percent had three or more high-risk features as defined by NCCN guidelines. This study demonstrated that the myPlan Lung Cancer test can identify high-risk patients that would have been otherwise designated as low risk according to NCCN pathological features. Importantly, in the Stage IB population, the myPlan test provided quantitative risk information above that determined by current NCCN high-risk features. Patients with resected Stage I lung adenocarcinoma and a high myPlan Lung Cancer score may be candidates for adjuvant therapy to reduce cancer-related mortality.

Poster Presentation: P3.04-084.
Title: Analytical Validation of a Proliferation-Based Signature Used as a Prognostic Marker in Early-Stage Lung Adenocarcinoma.
Date: Wednesday, Sept. 9, 2015: 9:45 to 10:45 a.m. and 3:45 to 4:45 p.m.

This study successfully validated the analytical performance of the myPlan Lung Cancer test using formalin-fixed paraffin embedded (FFPE) tissue samples from patients with lung cancer by assessing precision, dynamic range and RNA input requirements. The results showed that the test had a standard deviation of 0.06 score units, which is only one percent of the clinical range of scores, and demonstrates that the myPlan Lung Cancer test is highly reproducible. The positive results from this study form an important component of the analytical validation section in our reimbursement dossier.

About Myriad myPlan Lung Cancer

Myriad myPlan Lung Cancer is a molecular prognostic test that measures the expression levels of cell cycle progression genes to provide an accurate assessment of cancer aggressiveness in patients with early-stage non-small cell lung adenocarcinoma. For more information visit: View Source

On September 9, 2015 OncoMed Pharmaceuticals Inc. (NASDAQ:OMED), a clinical-stage company developing novel anti-cancer stem cell and immuno-oncology therapeutics, reported new biomarker and updated clinical data for the company’s Phase 2 anti-Notch2/3 therapeutic candidate, tarextumab (OMP-59R5) (Press release, OncoMed, SEP 9, 2015, View Source [SID:1234507431]). These data show the potential of Notch3 overexpression as a prognostic factor in small cell lung cancer and update OncoMed’s Phase 1b results for tarextumab in combination with standard-of-care chemotherapy for the first-line treatment of patients with extensive-stage disease. Anne Chiang, M.D., Ph.D., of the Yale School of Medicine, will present these data in a mini-oral presentation this afternoon at the 16th World Lung Conference on Lung Cancer.

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"Notch is known to be a fundamental cancer stem cell pathway driving the initiation and spread of tumors. Notch3 in particular has been associated with poor prognosis in a variety of solid tumor types, including pancreatic, breast and ovarian cancers," said Dr. Chiang. "Our analyses of small cell lung cancer patient tumors demonstrate that Notch3 overexpression in extensive-stage small cell lung cancer tumors is common and may be associated with poor survival. This is the first time that Notch3 tumor expression has been tested in small cell lung cancer and associated with poor patient outcomes."

A retrospective tumor microarray analysis that looked at Notch3 overexpression in 31 small cell lung cancer samples with available follow-up survival data showed that high levels of Notch3 protein expression appears to correlate with worse survival outcomes in patients with extensive-stage small cell lung cancer, elucidating for the first time that Notch3 may be an important prognostic factor in this solid tumor indication. Based on this analysis, prevalence of Notch3 overexpression in small cell lung cancer was estimated at 64 percent. This prevalence data is consistent with previously reported OncoMed biomarker data in small cell lung cancer.

"These new prognostic and prevalence observations for Notch3 provide a biological rationale for utilizing OncoMed’s anti-Notch 2/3 targeting antibody, tarextumab, in the small cell lung cancer indication," said Jakob Dupont, M.D., Chief Medical Officer of OncoMed. "In the clinic, we are seeing a consistent association between tarextumab dose and efficacy in our Phase 1b small cell lung cancer study. We’ve observed promising tumor response, biomarker and survival results among those small cell lung cancer patients who received doses of tarextumab above 10 mg/kg every three weeks. In a small number of patients, we are seeing that patients with Notch3 overexpressing tumors – where we might anticipate the worst outcomes – have the best survival rates, suggesting on-target activity. These data give us greater confidence that the 15 mg/kg every three week dose of tarextumab and the endpoints evaluating both all comer and tumor Notch3 high patient populations in our ongoing Phase 2 PINNACLE study are the right ones."

Overall survival data presented today from OncoMed’s Phase 1b study of tarextumab in combination with etoposide and platinum therapy for 23 patients with previously untreated extensive-stage small cell lung cancer show a correlation between dose and efficacy. Patients who received higher doses ( > 10 mg/kg) of tarextumab every three weeks plus chemotherapy demonstrated improved overall survival compared those who received lower doses. This durability of response was observed regardless of Notch3 gene expression status. Patients whose tumors tested biomarker positive for Notch3 expression and received higher doses of tarextumab with chemotherapy achieved the most benefit and a median overall survival for these patients has not yet been reached. These data expand on the findings of a dose-dependent relationship between tumor responses and survival among patients whose tumors were high in Notch3 expression that were reported at the 2015 ASCO (Free ASCO Whitepaper) Annual Meeting in June.

About the Phase 2 PINNACLE Trial

OncoMed is conducting the PINNACLE Phase 1b/2 clinical trial of tarextumab (anti-Notch 2/3, OMP-59R5) for the treatment of small cell lung cancer. The randomized Phase 2 trial will compare progression-free survival (PFS) outcomes for patients treated with tarextumab administered at 15 mg/kg every three weeks in combination with etoposide and cisplatin or carboplatin versus patients who receive chemotherapy alone. Additionally, PFS will be assessed using a predictive biomarker for high tumor Notch3 expression. Secondary endpoints for the Phase 2 study include overall survival, overall response rate, pharmacokinetics, safety and other biomarkers. The PINNACLE study is being conducted at about 40 sites in the U.S. and is expected to enroll approximately 130 patients. Results from the Phase 2 PINNACLE trial are anticipated in 2017.

About Small Cell Lung Cancer

According to the American Cancer Society, lung cancer (both small cell and non-small cell) is the second most common cancer in men and women and is by far the leading cause of cancer death. Small cell lung cancer is expected to make up about 10%-15% of the 221,200 newly diagnosed lung cancer cases and the 158,040 deaths estimated to occur in the U.S. in 20151. SCLC tends to grow and spread quickly, and is typically not discovered until it has metastasized to other parts of the body (extensive stage). The current standard of care in treating small cell lung cancer is the chemotherapeutic etoposide in combination with either cisplatin or caboplatin. In spite of a high sensitivity to chemotherapy and remission rates of up to 80% following initial treatment, the median overall survival is six-twelve months for patients with extensive stage disease2.

About Tarextumab (anti-Notch2/3, OMP-59R5)

Tarextumab (anti-Notch2/3, OMP-59R5) is a fully human monoclonal antibody that targets the Notch2 and Notch3 receptors. Preclinical studies have suggested that tarextumab exhibits two mechanisms of action: (1) by downregulating Notch pathway signaling, tarextumab appears to have anti-cancer stem cell effects, and (2) tarextumab affects pericytes, impacting stromal and tumor microenvironment. Tarextumab is currently being studied in two randomized Phase 2 clinical trials. The "ALPINE" study (Antibody therapy in first-Line Pancreatic cancer Investigating anti-Notch Efficacy and safety) is assessing tarextumab with Abraxane (paclitaxel protein-bound particles for injectable suspension) (albumin bound) plus gemcitabine in first-line advanced pancreatic cancer patients. The "PINNACLE" study (A Phase 1b/2 Study of OMP-59R5 in Combination with Etoposide and Platinum Therapy in Subjects with Untreated Extensive Stage Small Cell Lung Cancer) is testing tarextumab in combination with etoposide and cisplatin and etoposide and carboplatin in first-line extensive-stage small cell lung cancer patients. Tarextumab is part of OncoMed’s collaboration with GlaxoSmithKline (GSK). GSK has an option to obtain an exclusive license to tarextumab during certain time periods through completion of the proof-of-concept Phase 2 trials.