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IncellDx’s Quantitative Immuno-Oncology Assay OncoTect iO Published in New Study

On October 4, 2016 IncellDx, Inc., a single cell, precision medicine company, reported that the international peer-reviewed medical journal Cancer Immunology, Immunotherapy has published a manuscript entitled: "Quantification of PD-L1 and PD-1 expression on tumor and immune cells in non-small cell lung cancer (NSCLC) using non-enzymatic tissue dissociation and flow cytometry (Press release, IncellDx, OCT 4, 2016, View Source [SID:SID1234515589])." Dr. Bruce Patterson, MD, Founder and CEO explained that this is a novel, single cell approach to quantifying the expression of PD-L1 and PD-1 expression on tumor and immune cells in non-small cell lung cancer (NSCLC) tumor samples. The methodology has been validated on both fine needle aspiration (FNA) and tumor biopsies. The samples are non-enzymatically homogenized into single cell suspensions using IncellDx’s IncellPREP kit yielding a single-cell sample before a formalin-fixed paraffin embedded (FFPE) block is made.

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As Dr. Patterson explained, "We believe this objective quantitation of PD-L1 expression in tumor and immune cells in NSCLC will allow for better prediction of patient response to the new PD-1 immunotherapies within a work flow that is suited well for primary indications where the initial diagnosis may be made using several approaches to sampling the tumor. Further, the assay and sample preparation are automated allowing for same day turn around."

The PD-L1 and PD-1 assay is the first release of IncellDx, Inc.’s newest family of single cell, multi-parametric molecular products called OncoTect iO for immuno-oncology in a multitude of tissue types. The paper is now available online at View Source

Altor BioScience Corporation and NantKwest Inc. Announce Co-Development Agreement to Advance Innovative Natural Killer Cell Combination Immunotherapies for the Treatment of Cancer

On October 4, 2016 Altor BioScience Corporation (Altor), a leading developer of novel cytokine-based immunotherapeutics for cancer and infectious diseases and NantKwest Inc. (Nasdaq: NK), a clinical-stage immunotherapy company focused on harnessing the unique power of off-the-shelf Natural Killer (NK) cells to treat cancer, infectious diseases and inflammatory disorders reported the establishment of a co-development agreement focused on Altor’s lead candidates developed from its proprietary technology platforms, based on cytokines Interleukin-15 (IL-15) and Interleukin-2 (IL-2), that are currently in several Phase 1/2 clinical trials for hematologic and solid tumors (Press release, NantKwest, OCT 4, 2016, http://ir.nantkwest.com/phoenix.zhtml?c=254059&p=RssLanding&cat=news&id=2209112 [SID1234515586]).

Under the terms of the agreement, Altor and NantKwest will exclusively collaborate on the development of therapeutic applications combining Altor’s proprietary IL-15 superagonist (ALT-803) and its single-chain T cell receptor/IL-2 fusion protein (ALT-801) products with NantKwest’s proprietary NK cell therapy platforms for oncology indications. Financial terms of this co-development are not disclosed.

Hing C. Wong, Ph.D., Altor’s founder and CEO stated, "This partnership is a significant strategic collaboration for Altor and NantKwest. We believe there are significant opportunities to develop groundbreaking NK cell-based therapies using ALT-803 and ALT-801 in concert with NantKwest’s proprietary NK cell therapy and guided by a comprehensive genomic and proteomic molecular analysis using GPS cancer in the war against cancer. As Altor’s immunotherapeutic platform can play a key role in activating NK and T cells, we are enthusiastic to explore the synergy of this collaboration and rapidly advance clinical evaluation of these combination therapies in patients with cancer. Cell-based therapy combinations with Altor’s proprietary immunotherapeutics are an important component of our corporate strategy and we are excited to participate in the Cancer Moonshot 2020 program and the QUILT trials."

Patrick Soon-Shiong, M.D., FRCS (C), FACS, NantKwest’s CEO, commented, "Cell based therapies and comprehensive genomic, transcriptomic and proteomic analysis of the tumor tissue represents the future of precision immuno-oncology and the opportunity to bring the potential of 21st century medicine to patients today. As an off-the-shelf therapy, NantKwest’s proprietary, natural killer cell therapy offers a simple, easy-to-use therapy that we believe can become the standard of care for a broad range of cancer types. Recognizing the importance of omics guided (www.gpscancer.com) combination therapy to further improve therapeutic effectiveness and patient outcomes, the Cancer MoonShot 2020 program (www.cancermoonshot2020.org) was launched in January 2016 to bring together a wide range of novel therapeutic agents that can be utilized in novel, synergistic combinations. Altor’s ALT-803 and ALT-801 are two such therapeutic agents that offer the potential to be used in combination with NantKwest’s natural killer cell therapies to further improve therapeutic effectiveness and patient outcomes."

Five Prime Therapeutics Advances into Phase 1b Portion of Trial Evaluating the Immunotherapy Combination of Cabiralizumab (FPA008) and OPDIVO (nivolumab) in Multiple Tumor Types

On October 4, 2016 Five Prime Therapeutics, Inc. (Nasdaq:FPRX) a clinical-stage biotechnology company focused on discovering and developing innovative immuno-oncology protein therapeutics, reported that it has initiated the Phase 1b portion of the clinical trial evaluating the immunotherapy combination of cabiralizumab (FPA008), Five Prime’s investigational monoclonal antibody that inhibits colony stimulating factor-1 receptor (CSF1R), with OPDIVO (nivolumab), Bristol-Myers Squibb’s PD-1 immune checkpoint inhibitor, in multiple tumor types (Press release, Five Prime Therapeutics, OCT 4, 2016, View Source [SID:SID1234515585]).

"We are very pleased to progress to the Phase 1b portion of this trial evaluating cabiralizumab in combination with nivolumab as a treatment for patients with multiple types of tumors, many of whom currently have no effective treatment options," said Robert Sikorski, M.D., Ph.D., Chief Medical Officer, at Five Prime. "Our goal is to develop new therapeutics that unleash the immune system’s natural anti-cancer activity. Based on the science, we believe that targeting both the CSF1R and PD-1 pathways has the potential to produce a synergistic treatment effect."

Five Prime initiated the Phase 1a/1b trial, which is expected to enroll approximately 280 patients, in September 2015. During Phase 1a, Five Prime evaluated the safety, pharmacokinetics and biomarkers of escalating doses of cabiralizumab as a monotherapy, as well as in combination with the approved 3 mg/kg dose of nivolumab.

Five Prime will continue to run the Phase 1b portion of the trial and will evaluate the safety, tolerability and preliminary efficacy of the selected dose of cabiralizumab in combination with nivolumab for the treatment of advanced solid tumors, including but not limited to non-small cell lung cancer, squamous cell carcinoma of the head and neck, pancreatic cancer, glioblastoma, renal cell carcinoma and ovarian cancer.

About Cabiralizumab (FPA008)
Cabiralizumab is an investigational antibody that inhibits the CSF-1 receptor and has been shown in preclinical models to block the activation and survival of monocytes and macrophages. Inhibition of CSF1R in preclinical models of several cancers reduces the number of immunosuppressive tumor-associated macrophages (TAMs) in the tumor microenvironment, thereby facilitating an immune response against tumors. Cabiralizumab is currently in a Phase 2 clinical trial in pigmented villonodular synovitis (PVNS) and a Phase 1 clinical trial in oncology indications. Cabiralizumab is being developed under an exclusive worldwide license and collaboration agreement entered into with BMS in October 2015.

EXCLUSIVE LICENSING AGREEMENT FOR IN-HOUSE DEVELOPED MONOCLONAL ANTIBODY FARLETUZUMAB IN LATIN AMERICA CONCLUDED WITH EUROFARMA LABORATÓRIOS S.A.

On October 4, 2016 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported that its research subsidiary Morphotek, Inc. (Headquarters: Pennsylvania, United States, President and CEO: Nicholas Nicolaides, "Morphotek") has signed an exclusive licensing agreement with Eurofarma Laboratórios S.A. (Headquarters: São Paulo, Brazil, President: Maurizio Billi, "Eurofarma") to develop and commercialize the monoclonal antibody farletuzumab (development code: MORAb-003) as a potential anticancer agent in Latin America (Press release, Eisai, OCT 4, 2016, View Source [SID:SID1234515584]).

Under the terms of the agreement, Morphotek will receive from Eurofarma an upfront payment as well as scheduled development and sales milestone payments. Additionally, Morphotek will receive royalties from commercial sales of farletuzumab in Latin America. Morphotek will supply Eurofarma with clinical and commercial materials while Eurofarma has the option to assume responsibility for filling and packaging farletuzumab vials. Morphotek retains all rights to develop and commercialize farletuzumab in regions outside of Latin America.

Discovered by Morphotek, farletuzumab is an investigational, humanized, monoclonal antibody that binds to folate receptor alpha (FRA), which is reported to be highly expressed on ovarian and several other epithelial cancer cells, but mostly absent from normal tissue. Farletuzumab is currently being studied in a randomized, placebo-controlled, double-blind Phase II clinical study in first-relapsed, platinum-sensitive ovarian cancer patients with low levels of the CA-125 tumor antigen, a biomarker for ovarian cancer. The study is designed to investigate the efficacy and safety of farletuzumab in combination with standard chemotherapy.

Eisai positions oncology as a key therapeutic area, and is aiming to discover revolutionary new medicines with the potential to cure cancer. Through this collaboration, Eisai hopes to accelerate development and maximize the value of farletuzumab as it seeks to contribute further to addressing the diverse needs of, and increasing the benefits provided to, patients with cancer, their families, and healthcare providers.

US FDA grants Breakthrough Therapy Designation for Roche’s Alecensa (alectinib) for first-line treatment of people with ALK-positive NSCLC

On October 4, 2016 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that it has received a second Breakthrough Therapy Designation (BTD) from the United States Food and Drug Administration (FDA) for its ALK inhibitor, Alecensa (alectinib) (Press release, Hoffmann-La Roche , OCT 4, 2016, View Source [SID:SID1234515583]). The latest BTD was granted for the treatment of adult patients with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) who have not received prior treatment with an ALK inhibitor.

"The J-ALEX study that supports the second Breakthrough Designation for Alecensa showed superior efficacy versus the standard of care, crizotinib, in Japanese people with advanced ALK-positive disease," said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development. "The decision by the FDA to grant a second breakthrough therapy designation is recognition of the clinically meaningful improvement in efficacy and safety that Alecensa brings to the care of people with advanced ALK-positive lung cancer who have not received prior treatment with an ALK inhibitor."

This second breakthrough therapy designation is based on the results of the open-label, randomised phase III J-ALEX study, which were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2016 Annual Meeting in June. J-ALEX compared the efficacy and safety of Alecensa with crizotinib in 207 Japanese people with ALK-positive, advanced or recurrent NSCLC who either had not been treated with chemotherapy or had received one prior line of chemotherapy. Results from the study demonstrated that Alecensa reduced the risk of disease worsening or death (progression-free survival, PFS) by 66% compared to crizotinib, whilst maintaining a favourable tolerability and safety profile consistent with that observed in previous studies.

The FDA’s Breakthrough Therapy Designation is designed to expedite the development and review of medicines intended to treat serious diseases and to help ensure patients have access to them through FDA approval as soon as possible. Alecensa received its first FDA BTD in June 2013 for people with ALK-positive NSCLC whose disease progressed on treatment with crizotinib.

Alecensa is currently available in the US and Israel to ALK-positive metastatic NSCLC patients who have progressed on or are intolerant to crizotinib, and in Japan to ALK-positive unresectable, recurrent or advanced NSCLC patients. In addition, an ongoing global, randomised phase III trial called ALEX is comparing Alecensa to Xalkori as an initial (first-line) treatment for people with advanced ALK-positive NSCLC.

About J-ALEX
The J-ALEX study conducted by Chugai is an open-label, randomised Phase III study that compared the efficacy and safety of Alecensa to crizotinib in Japanese people. The J-ALEX study enrolled 207 people with ALK-positive, advanced or recurrent NSCLC who had not been previously treated with an ALK inhibitor. People were randomised to the Alecensa group or the crizotinib group in a one-to-one ratio. Results include:

Alecensa reduced the risk of disease worsening or death (PFS) by 66 percent compared to crizotinib (HR=0.34, 99 percent CI: 0.17-0.70, p<0.0001).

Median PFS was not reached in the Alecensa arm (95 percent CI: 20.3 months-not estimated) versus 10.2 months in the crizotinib arm (95 percent CI: 8.2-12.0).

Grade 3-4 adverse events (AE) occurred with lesser frequency in the Alecensa arm compared to the crizotinib arm (27 percent vs. 51 percent).

The most common AE occurring with > 30 percent frequency with Alecensa was constipation (36 percent). The most common AEs for crizotinib were nausea (74 percent), diarrhoea (73 percent), vomiting (59 percent), visual disturbance (55 percent), alteration in taste (dysgeusia, 52 percent), constipation (46 percent), and an elevation in liver enzymes called alanine transaminase (ALT, 32 percent) and aspartate transaminase (AST, 31 percent).

About Alecensa
Alecensa (RG7853/AF-802/CH5424802) is an oral medicine created at Chugai Research Laboratories and is being developed for people with NSCLC whose tumours are identified as ALK-positive. ALK-positive NSCLC is often found in younger people who have a light or non-smoking history. It is almost always found in people with a specific type of NSCLC called adenocarcinoma. Alecensa is currently approved in the United States for the treatment of people with advanced (metastatic) ALK-positive NSCLC whose disease has worsened after, or who could not tolerate treatment with, crizotinib.

In two key phase II studies, NP28761 and NP28673, Alecensa shrank tumours in up to 44% of people with ALK-positive NSCLC who progressed on crizotinib. Alecensa also demonstrated activity in brain metastases, indicating that the drug may be taken up in the brain. The brain is protected by the Blood-Brain
Barrier, a network of tightly joined cells that line the inside of the blood vessels in the brain and spinal cord.

One of the ways the Blood-Brain Barrier prevents molecules from affecting the brain is to actively eject them from the barrier through a process known as ‘active efflux’. The active efflux system does not recognise
Alecensa, which means that it may travel into and throughout brain tissue.

The global phase III studies of Alecensa include a companion test developed by Roche Diagnostics. Alecensa is marketed in Japan by Chugai Pharmaceutical, a member of the Roche Group.

About ALK-positive non-small cell lung cancer
Lung cancer is the biggest cancer killer, causing 1.59 million deaths globally each year. NSCLC is the most common type of lung cancer, and is the leading cause of cancer-related deaths in Europe and across the world, accounting for approximately 85% of lung cancer cases. ALK-positive NSCLC occurs in approximately 5% of patients with advanced NSCLC, translating to about 75,000 patients being diagnosed with the disease annually. It is almost always found in people with a specific type of NSCLC called adenocarcinoma, and is more common in light or non-smokers.