On September 8, 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 it has initiated patient dosing in the Phase 1a/1b clinical trial evaluating the immunotherapy combination of FPA008, Five Prime’s monoclonal antibody that inhibits colony stimulating factor-1 receptor (CSF1R), with OPDIVO (nivolumab), Bristol-Myers Squibb’s PD-1 immune checkpoint inhibitor, in six tumor types (Press release, Five Prime Therapeutics, SEP 8, 2015, View Source [SID:1234507422]).

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FPA008 and OPDIVO are part of a new class of cancer treatments known as immunotherapies that are designed to harness the body’s own immune system to fight cancer. FPA008 targets macrophages and monocytes, which are activated or elevated in multiple disease settings. In cancer, tumor-associated macrophages suppress the immune system’s ability to kill cancer cells. OPDIVO is approved in the United States, Japan and the European Union for metastatic melanoma, and in the United States and European Union for squamous non-small cell lung cancer. OPDIVO is being evaluated as a mono therapy, as well as in combination with other agents, across multiple tumor types in more than 50 clinical trials. Preclinical data suggest that combining antibodies targeting PD-1 and CSF1R may lead to an enhanced anti-tumor immune response compared to either drug alone.

"We hope that targeting tumor suppressing macrophages in addition to a known immune checkpoint will allow us to harness more of the immune system’s anticancer activity, and will make durable responses a reality for more of our patients," said Julie Brahmer, M.D., Associate Professor of Oncology and Interim Director at the Sidney Kimmel Comprehensive Cancer Center (Johns Hopkins Bayview campus) and a Principal Investigator for the trial. "We look forward to participating in this trial, which will generate important information about the potential of this immunotherapy combination across a number of tumor types, including many where patients have few effective treatments."

"We are excited about the potential of FPA008 as a novel immuno-oncology therapeutic and about combining it with OPDIVO in this clinical collaboration with Bristol-Myers Squibb. We believe that targeting the CSF1R and PD-1 pathways in tandem may produce a synergistic treatment effect against a variety of tumors," said Lewis T. "Rusty" Williams, M.D., Ph.D., president and chief executive officer of Five Prime. "Five Prime looks forward to enrolling this study, as it will provide us a wealth of information about this novel therapeutic combination and will further guide our development of FPA008 in oncology."

During Phase 1a, Five Prime will evaluate the safety, pharmacokinetics and biomarkers of escalating doses of FPA008 as a monotherapy, as well as in combination with the approved 3 mg/kg dose of nivolumab. Approximately 30 patients with advanced cancers are expected to be enrolled during the Phase 1a part of the study and both drugs will be administered every two weeks. In the Phase 1b part of the study, Five Prime will evaluate the safety, tolerability and preliminary efficacy of the selected dose of FPA008 in combination with nivolumab in approximately 240 patients, as a front-line therapy for melanoma; as second-line therapy for squamous cell carcinoma of the head and neck, pancreatic cancer, and malignant glioma; as a second- or third-line therapy for non-small cell lung cancer (NSCLC); and as a third-line therapy for colorectal cancer. Tumor biopsies will be obtained both pre-treatment and one month post-treatment in a subset of patients to analyze the immune response within the tumor microenvironment, and Five Prime will use this analysis to further guide FPA008’s development in oncology.

Under the terms of the clinical collaboration, BMS made a one-time payment of $30 million to Five Prime and is responsible for external study costs, the costs for OPDIVO, and half of the costs for FPA008 used in the Phase 1b part of the trial. The study design will be described in further detail in a trial-in-progress presentation at the International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper), to be held September 16-19, 2015 in New York City. Five Prime expects to complete Phase 1a dose escalation and expand into Phase 1b with the selected dose of FPA008 in late 2015 or early 2016.

About FPA008

FPA008, Five Prime’s antibody that inhibits colony stimulating factor-1 receptor (CSF1R), targets macrophages and monocytes, which are activated or elevated in multiple disease settings. In cancer, tumor-associated macrophages suppress the immune system’s ability to kill cancer cells. In joint diseases, such as PVNS and RA, synovial macrophages play a central role in the disease process. Five Prime is evaluating the immunotherapy combination of FPA008 and OPDIVO (nivolumab), Bristol-Myers Squibb’s investigational PD-1 immune checkpoint inhibitor, in six tumor types in a Phase 1a/1b clinical trial. Five Prime is also conducting a Phase 1/2 trial of FPA008 in pigmented villonodular synovitis (PVNS), a joint tumor driven by the CSF1 pathway and an orphan disease, and a Phase 1 study in rheumatoid arthritis.

On September 8, 2015 Aduro Biotech, Inc. (Nasdaq:ADRO) reported that it has completed enrollment in the Phase 2b ECLIPSE trial of its novel LADD and GVAX immunotherapies being developed for the treatment of metastatic pancreatic cancer. The randomized, controlled three-arm trial enrolled 303 patients in the United States and Canada (Press release, Aduro BioTech, SEP 8, 2015, View Source;p=RssLanding&cat=news&id=2085917 [SID:1234507460]). Top line results are expected in the first half of 2016.

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ECLIPSE was designed to evaluate the safety, immune response and efficacy of the combination immunotherapy of CRS-207 and GVAX Pancreas compared to chemotherapy. The trial also included a treatment arm to evaluate CRS-207 as a monotherapy. The primary endpoint of the trial is overall survival in the primary cohort of patients who have received two or more prior therapies for metastatic disease. A second cohort of patients who received one prior therapy for metastatic disease is also being evaluated.

"This is a significant clinical trial in the pancreatic cancer field which has the potential to yield important information on the role of Aduro’s immunotherapy combination in this indication," said Vincent Picozzi, M.D., director of the Pancreatic Center of Excellence at the Virginia Mason Clinic. "Very few therapeutic options exist for metastatic pancreatic cancer patients, especially after initial chemotherapy, and this field could benefit greatly from more varied and attractive therapy options."

"The fight against metastatic pancreatic cancer continues to be arduous," said Dirk G. Brockstedt, Ph.D., senior vice president of research and development at Aduro. "We are encouraged by data from long-term survivors in our Phase 2a clinical trial and look forward to results from our Phase 2b ECLIPSE trial. We would like to thank our investigators, and more importantly the patients and their families, for their participation and support in our trials and development of our technologies in this indication."

The ECLIPSE trial was initiated following a Phase 2a trial which demonstrated efficacy of the immunotherapy combination with CRS-207 and GVAX Pancreas compared to GVAX Pancreas alone in a randomized, controlled, multi-center trial in metastatic pancreatic cancer patients. Results of the Phase 2a clinical trial, published in the Journal of Clinical Oncology (JCO), indicated the median overall survival of Arm A patients receiving the combination regimen of CRS-207 and GVAX Pancreas was 6.1 months compared to 3.9 months for Arm B patients receiving GVAX monotherapy (HR=0.5930, one-sided p=0.0172).

Overall, the combination immunotherapy was well-tolerated. Of the 93 patients enrolled, the most common Grade 3 adverse events were transient lymphopenia, fevers, elevated liver enzymes and fatigue.

In 2014, the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation for Aduro’s pancreatic cancer combination treatment consisting of CRS-207 and GVAX Pancreas based on results from the Phase 2a clinical trial of patients with metastatic pancreatic cancer. According to the FDA, Breakthrough Therapy designation is for a drug candidate that treats a serious or life-threatening condition for which preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on a clinically significant endpoint over available therapies.

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.

About GVAX Pancreas

GVAX Pancreas is one of a family of GVAX immunotherapies derived from human cancer cell lines that are genetically modified to express granulocyte-macrophage colony-stimulating factor (GM-CSF), an immune system-stimulating cytokine. GVAX Pancreas is derived from human pancreatic cancer cell lines and is designed to activate specific T cell immunity to pancreatic cancer antigens, including mesothelin.

On September 8, 2015 Kancera reported it has entered into an agreement with Acturum Life Science AB in order to evaluate and further develop the unique Fractalkine inhibitor AZD8797 (Press release, Kancera, SEP 8, 2015, View Source [SID:1234511323]). Published research points to that Fractalkine signaling probably contributes to the growth and spread of tumors and the pain that often affects cancer patients. In addition, the presence of Fractalkine has been proposed to be associated with a lack of efficacy of immuno-oncology drugs. Taken together, these findings provide a new perspective of Fractalkine signaling as a target for cancer drug development. Kancera will now evaluate how efficiently the Fractalkine inhibitor AZD8797 may stop tumor growth and relieve severe pain.

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Originally, the candidate drug AZD8797 was successfully developed by AstraZeneca in Södertälje as an effective inhibitor of Fractalkine signaling. The present documentation of AZD8797 includes drug properties, safety, toxicology, and production. Kancera’s assessment is that this documentation is likely to meet requirements for an application to undertake clinical trials against cancer. AstraZeneca originally developed AZD8797 against multiple sclerosis and showed effect of AZD8797 in a preclinical model of the disease (see the publication in PNAS April 8, 2014 vol. 111, no. 14, p 5409). Acturum Life Science acquired the rights to the Fractalkine project from AstraZeneca as part of Acturum’s acquisition of the research facility in Södertälje. However, AstraZeneca has retained the rights to develop Fractalkine inhibitors against respiratory diseases.

The agreement with Acturum Life Science gives Kancera right to evaluate AZD8797 in preclinical studies and then to acquire the project. This agreement entails no expenses for Kancera apart from investments in the patent portfolio and in the scientific evaluation.

If Kancera chooses to acquire the Fractalkine project, following the preclinical evaluation phase, the total payment to Acturum will consist of 6 million Kancera shares divided into three tranches, which are due at pre-defined success-milestones. Accordingly, the two companies share the risk in the product development through the first study in man. Kancera intends to apply for orphan drug designation, covering the Fractalkine inhibitor, in order to ensure at least 10 years of exclusivity on the market in Europe and 7 years in the United States.

Since AZD8797 already meets the pharmaceutical properties Kancera considers necessary for the biological evaluation of the effect against cancer, the project can be run without significantly affecting the resource allocation to Kancera’s other projects.

"The agreement with Acturum provides Kancera with a technically strong candidate drug in an dynamic field of drug discovery. We are thereby set to evaluate how the promising research on Fractalkine can be translated into a new effective immune-oncology treatment" says Thomas Olin, CEO of Kancera.

Peter Sjöstrand, representing Acturum Life Science AB and its main shareholder FAM (the Wallenberg Foundations’ investment company) continues, "the agreement with Kancera provides the best conditions for a professional evaluation and further development of the Fractalkine project in a very important medical area. Since Acturum is committed to keep the Kancera shares received as payment for the project for at least five years, the agreement is also the start of a long-term commitment in Kancera. "

About the Fractalkine project
Fractalkine is an immune regulatory factor that sends signals via the CX3CR1 receptor, also called G-protein coupled receptor 13 (GPCR13). In the healthy individual, Fractalkine and its receptor regulate migration of immune cells from the blood capillary wall into areas where the immune system is needed. Animal studies show that Fractalkine and its receptor are not essential for survival and that important immune functions remain intact indicating that inhibition of the Fractalkine signaling by a drug probably will be tolerated without significant adverse effects. Fractalkine and its receptor have been linked to the growth and proliferation of pancreatic, breast and prostate cancer. Also, cancer cells that have the Fractalkine receptor on their surface migrate towards nerve ends that have Fractalkine on their surface. Thus, cancer cells are led to surround and apply pressure on nerves and thereby cancer pain may arise. Another proposed mechanism for how Fractalkine and its receptor affect the development of tumors is that they contribute to the transformation of the body’s macrophages from being a threat against the cancer (the M1 form) to supporting the cancer (the M2 form). This mechanism is also suggested as a predictive factor for responsiveness to the new immuno-oncology drugs that act through PD-1 and PD-L1 such as nivolumab, pembrolizumab and pidilizumab. During 2014 and 2015 studies have been published demonstrating that the absence of Fractalkine in tumor cells is a significant marker for how successful the immuno-oncology treatment is expected to be (see e.g. the publication in Nature on November 27, 2014, Vol. 515, pp 563). In the light of these observations, there are good reasons to further study if inhibition of the Fractalkine signaling with AZD8797 has the potential to increase the proportion of patients responding to the new immuno-oncology drugs that act through PD-1 and PD-L1.

On September 7, 2015 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported that data from 138 abstracts will be presented at this year’s European Cancer Congress (ECC) from Sept. 25 – 29 in Vienna, Austria (Press release, Genentech, SEP 7, 2015, View Source [SID:1234507412]). Results will be presented from several clinical studies that are supporting ongoing regulatory discussions for three investigational medicines across specific types of lung, bladder and skin cancer (alectinib, atezolizumab and cobimetinib, which recently received its first approval in Switzerland where it is marketed as Cotellic). Building on its large portfolio of approved cancer medicines, these regulatory discussions represent significant progress for Genentech’s pipeline in the fields of cancer immunotherapy and targeted medicines.

"With our targeted medicines, cancer immunotherapies and the combination potential in our portfolio, we are committed to setting new standards for treating people with cancer," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "At the 2015 European Cancer Congress, new data will be presented for three investigational medicines that we hope will be approved within the next year, including atezolizumab for people with PD-L1 expressing lung and bladder cancers."

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In addition to data for alectinib, atezolizumab and cobimetinib, results will be presented across multiple tumor types from Genentech’s cancer immunotherapy and targeted medicines pipeline including CEA-IL2v (RG7813), IDO Inhibitor (GDC-0919) and vanucizumab (anti-Ang2/VEGF, RG7221). The table below contains key abstracts featuring Genentech medicines, including late breaking abstracts that will be presented during the Congress.

Follow Genentech on Twitter via @Genentech and keep up to date with the 2015 European Cancer Congress news and updates by using the hashtag #ECC2015.

On September 8, 2015 Boehringer Ingelheim reported that the Global Lung Cancer Coalition (GLCC) presented, at the 16th World Conference on Lung Cancer (WCLC) in Denver, USA, results of Lung Cancer: We’re Listening, a global campaign, supported by Boehringer Ingelheim (Press release, Boehringer Ingelheim, SEP 7, 2015, View Source [SID:1234507407]). The global survey intended to increase knowledge and understanding of real world challenges facing lung cancer patients and their carers. The data showed 64% of lung cancer patients and 55% of carers identified that daily life challenges, such as emotional and social issues, were more significant than medical care challenges such as diagnosis and treatment planning.1 The findings of the survey highlight the need for a more holistic approach to lung cancer care.

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Aoife McNamara, a specialist oncology nurse with the Irish Cancer Society said, "Lung cancer is the world’s biggest cancer killer, sadly the majority of patients are diagnosed at an advanced stage so addressing the medical challenges faced by patients can often be the focus of care. However the Lung Cancer: We’re Listening survey highlighted that challenges related to everyday life were often the biggest burden and as advancements in medical care continue it is paramount that there is an equal emphasis on helping patients cope with the day-to-day struggles of lung cancer. Daily life challenges need to be routinely identified and alleviated to ensure those affected by lung cancer receive the necessary spectrum of support and information to help improve patient’s lives."

The GLCC and Boehringer Ingelheim collaborated in 2013 to launch Lung Cancer: We’re Listening, a global online survey to identify the priorities and variety of challenges faced by lung cancer patients and their caregivers. Respondents included 725 patients and carers who identified their most significant challenge related to lung cancer from 200 specific challenges. The specific challenges, which had been identified by GLCC lung cancer experts, were grouped into categories and illustrated with a short text descriptor.

Daily life challenges in the category of ‘emotional and social needs’ were deemed to be the most significant with 19% of respondents affected by challenges such as expressing and sharing feelings, dealing with stigma and developing coping strategies.1 Medical care challenges in the category of ‘diagnosis’ were the most significant with 20.5% of respondents affected by challenges such as molecular tumour testing, getting a second opinion and misdiagnosis.1

More than half of patients and carers indicated their lack of ability to cope with the challenges they face, with 50.8% stating they were either unable to cope or could only cope sometimes; 56.2% of respondents stated they needed information related to the specified challenge and over a quarter (25.5%) needed a lot of help or support from either a professional or caregiver.1

Dr Jörg Barth, Corporate Senior Vice President, Therapy Area Head Oncology, Boehringer Ingelheim said, "Boehringer Ingelheim is committed to improving the treatment and the lives of patients who suffer from lung cancer as demonstrated by this important initiative. We would like to extend our thanks to the GLCC for the Lung Cancer: We’re Listening initiative and are proud to have supported it.The results deepen our understanding of the importance of supporting lung cancer patients and their carers. We will continue to support the ongoing work of the GLCC to improve the lives of patients with lung cancer, ensuring their needs are at the heart of a holistic approach to care which shifts the current paradigm beyond medical treatment."

About ‘Lung Cancer: We’re Listening’
In 2013, The Global Lung Cancer Coalition (GLCC) and Boehringer Ingelheim collaborated to create a global online survey to identify the priorities and variances in challenges faced by the lung cancer patient and carer community.

Lung cancer experts from the GLCC identified 200 challenges faced by lung cancer patients and carers, which were related to either medical care or daily life, grouped into sub-categories and illustrated with a short text descriptor. At survey entry, respondents identified their greatest challenge as relevant to either daily life or medical care and chose subsequent sub-categories of challenges, until one distinctive challenge was identified as being the most significant.

For more information on the survey methodology and results please visit: