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Aduro Biotech Announces Clinical Trial Agreement to Evaluate Combination of Two Novel Cancer Immunotherapies for the Treatment of Ovarian Cancer

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.

8-K – Current report

On September 9, 2015 Mirati Therapeutics, Inc. ("Mirati") (NASDAQ: MRTX), an oncology company focusing on genetic and epigenetic drivers of cancer, reported it will present data at the International Association of Lung Cancer (IASLC) 16th World Conference on Lung Cancer on the first non-small cell lung cancer (NSCLC) patient with AXL gene amplification enrolled in the MGCD265 Phase 1b expansion cohort (Filing, 8-K, Mirati, SEP 9, 2015, View Source [SID:1234507446]). Data will be presented showing the patient had a confirmed Partial Response (PR) based on RECIST criteria. Additionally, the Company announced a confirmed PR in a NSCLC patient with MET gene amplification who was enrolled in the MGCD265 expansion cohort.

"Out of four non-small cell lung cancer patients whom have had at least one scan in the ongoing MGCD265 expansion cohort, two patients have RECIST-confirmed PRs. Those PRs, together with tumor regressions seen in all four of these patients, demonstrate the potentially significant clinical benefit of MGCD265 in patients with lung cancer," said Charles M. Baum, M.D., Ph.D., President and CEO, Mirati. "The study is progressing well due to the enthusiasm of the clinical investigators, and this has resulted in increased screening and enrollment at the clinical trial sites. Currently, nine patients with MET or AXL genetic alterations have been enrolled in the study. In light of the dramatic response being presented in the patient with AXL gene amplification at today’s World Conference on Lung Cancer, we felt it was appropriate to provide an interim update on the program. As previously indicated, we will provide a more in-depth update when we have additional data."

NSCLC Patient with Axl Gene Amplification

The male patient was diagnosed with metastatic adenocarcinoma of the lung, with multiple tumors in both lungs which had spread to the lung cavity and lymph nodes. Prior to treatment with MGCD265, he had received multiple chemotherapies, as well as an experimental agent combined with chemotherapy, with the best response being disease progression. After 2 cycles of treatment with MGCD265, tumor imaging showed a PR with a tumor reduction of 42.3% compared to baseline. After 4 cycles of treatment, the PR was confirmed with a tumor reduction of 48.8% based on RECIST criteria. The patient, who remains on study in Cycle 7, also showed improvement in clinical symptoms. Prior to starting treatment with MGCD265, the patient was oxygen dependent. Shortly after treatment with MGCD265, he was off oxygen and able to ride his bike up to seven miles per day.

"To our knowledge, this is the first reported case of an objective response in a patient with a tumor harboring AXL gene amplification," said Geoffrey Shapiro, Principal Investigator and Director of the Early Drug Development Center, Department of Medical Oncology, Dana-Farber Cancer Institute. "This response, coupled with the patient’s significant symptomatic improvement, provides clinical validation that AXL genomic alterations can result in oncogene addiction in patients with non-small cell lung cancer. We will continue to explore MGCD265, a potent kinase inhibitor, in patients with MET or AXL genomic alterations, in an effort to improve cancer treatment by targeting genetic drivers of cancer."

Data from the study will be presented on September 9, 2015 in an oral presentation titled, "Evaluation of the MET/Axl Receptor Tyrosine Kinase (RTK) Inhibitor MGCD265 in a Patient with Metastatic Non-Small Cell Lung Cancer (NSCLC) Harboring AXL Amplification" by Lynette Sholl, M.D, Assistant Professor, Translational Research Group, Brigham and Women’s Hospital. The presentation is part of the New Kinase Targets session, Treatment of Advance Diseases – NSCLC track (abstract # 3611) from 6:30 – 8:00 PM MT/5:30 – 7:00 PM PT in Colorado Convention Center, Four Seasons Ballroom F3+F4.

Interim Update on the Ongoing MGCD265 Phase 1b Expansion Cohort

MGCD265 is an inhibitor of the MET and Axl receptor tyrosine kinases which, when mutated or amplified, can be drivers of tumor growth. Preclinical data have shown that MGCD265 can potently inhibit tumor cell growth in vitro, and demonstrate marked tumor regression in tumor xenograft models exhibiting MET gene amplification and MET exon 14 deletions.

This multi-national, multi-site, open label, single agent study is designed to evaluate the safety, pharmacokinetics/pharmacodynamics and clinical activity of twice-daily MGCD265 in patients who have failed at least one prior therapy. The study continues to enroll patients with MET or AXL gene alterations. MGCD265 has been well tolerated at the recommended Phase 2 dose, which has demonstrated full inhibition of both MET and Axl tyrosine kinases, and is the only kinase inhibitor that we know of in clinical development that has demonstrated potent and selective inhibition of both MET and Axl.

As of September 1, 2015, 9 patients with genetic alterations in MET or AXL have been enrolled in the expansion cohort, including 7 with NSCLC and 2 with other solid tumors. The Company disclosed that 2 of the 4 NSCLC patients, who are currently evaluable (having had at least 1 on-treatment scan), have confirmed PRs based upon RECIST criteria, including the patient with AXL amplification highlighted above and a patient with MET gene amplification. Both patients remain on study. All 4 of the evaluable NSCLC patients showed clinically significant tumor regressions. Of the 9 patients enrolled, 7 remain on study for up to 8+ months.

About MET and Axl in NSCLC

MET is highly expressed in NSCLC tumors. Extensive preclinical and emerging clinical data indicate that MET is a driver of tumor growth when it is genetically altered by point mutations, exon 14 deletion mutations, and/or gene amplification in a significant fraction (6-7%) of NSCLC patients. MET gene amplification and MET mutations, including exon 14 deletion mutations, each exhibit the key characteristics of driver oncogenes in NSCLC.

Axl is over-expressed in patients with advanced NSCLC and has been associated with poor prognosis. Amplification and rearrangements of the AXL tyrosine kinase gene also appear to be a driver of tumor growth and occur in up to 2% of patients with NSCLC. Preclinical data has shown that dysregulation of Axl is implicated in tumor progression and resistance to standard and targeted cancer therapies. Extensive preclinical and clinical data also indicate that both MET and Axl are important factors in resistance to EGFR inhibitors, as well as the third-generation EGFR inhibitors.

About MGCD265

MGCD265 is a tyrosine kinase inhibitor that potently and selectively targets tumors in patients with driver alterations in MET (gene amplification and mutations) and AXL (gene amplification and rearrangements) that occur in approximately 8% of patients with non-small cell lung cancer (NSCLC). MGCD265 is in the expansion phase of a Phase 1/1b dose escalation study for NSCLC patients with MET or AXL genetic alterations. Genetic alterations in these targets have been implicated as drivers of tumor growth and disease progression in NSCLC, gastroesophageal cancer and other solid tumors. Mirati retains worldwide rights to MGCD265.

Peregrine Pharmaceuticals Reports Financial Results for First Quarter of Fiscal Year 2016 and Recent Developments

On September 9, 2015 Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM) (NASDAQ:PPHMP), a biopharmaceutical company focused on developing therapeutics to stimulate the body’s immune system to fight cancer, reported financial results for the first quarter of fiscal year (FY) 2016 ended July 31, 2015, and provided an update on its advancing clinical pipeline and other corporate developments (Press release, Peregrine Pharmaceuticals, SEP 9, 2015, View Source [SID:1234507437]).

Highlights Since April 30, 2015:
"Over the years, Peregrine’s foundational science and positive clinical results have consistently pointed to bavituximab’s potential as a high-value, next-generation anti-cancer agent," said Steven W. King, president and chief executive officer of Peregrine. "In the last three months, these achievements have compelled others to align with us as we continue to develop bavituximab. In May, Peregrine announced an exciting collaboration with Memorial Sloan Kettering Cancer Center to evaluate combinations of bavituximab with other checkpoint inhibitors and immune stimulatory agents for the purpose of developing new and increasingly effective anti-cancer treatments. Only three months later, we announced a collaboration with AstraZeneca to clinically evaluate bavituximab in combination with AstraZeneca’s investigational anti-PD-L1 immune checkpoint inhibitor, durvalumab (MEDI4736) in multiple solid tumors. These collaborations with world leaders in immuno-oncology speak to the promise of bavituximab and validate our ever-growing enthusiasm for the investigational product. We look forward to advancing both of these programs and completing enrollment of our SUNRISE trial in the next few months."

Clinical Development Highlights
Peregrine and AstraZeneca entered into a cancer immunotherapy clinical trial collaboration to evaluate bavituximab in combination with AstraZeneca’s investigational anti-PD-L1 immune checkpoint inhibitor, durvalumab (MEDI4736). The planned Phase I/Ib trial will evaluate the safety and efficacy of bavituximab in combination with durvalumab in multiple solid tumors. Peregrine is working closely with AstraZeneca to finalize the trial design.

Phase III SUNRISE clinical trial in non-small cell lung cancer (NSCLC) continues to enroll patients and remains on track to complete patient enrollment by end of calendar year 2015.

Peregrine announced plans to expand the bavituximab clinical development program to include a Phase II trial to evaluate the combination of bavituximab and Opdivo (nivolumab), an anti-PD-1 antibody, in previously treated, metastatic NSCLC. This trial is expected to be initiated by the end of calendar year 2015.

Peregrine announced plans to expand the bavituximab clinical development program to include a Phase II/III trial to evaluate bavituximab with chemotherapy combinations in HER2-negative metastatic breast cancer. This trial is expected to be initiated by the end of calendar year 2015.

Supportive Research Highlights
Peregrine and Memorial Sloan Kettering Cancer Center entered into a research agreement to explore the potential of Peregrine’s proprietary PS-targeting antibody platform. The goal of the research is to identify effective treatments combining bavituximab with other checkpoint inhibitors or immune stimulating agents.

New data presented at the International Association for the Study of Lung Cancer’s (IASLC’s) World Conference on Lung Cancer (WCLC) from a translational study of bavituximab demonstrated the ability of bavituximab, alone or in combination with docetaxel, to induce signs of immune activation in non-small cell lung cancer (NSCLC) patient-derived tumor samples, particularly when there was negative PD-L1 expression in the tumor sample. These data further support the potential mechanistic synergies for bavituximab with chemotherapy and checkpoint inhibitors targeting the PD-1/PD-L1 pathway.

Summary data presented at the Combination Immunotherapy Strategies session at the 10th Annual Immunotherapy and Vaccine Summit (ImVacS), highlighted key findings from several recent bavituximab-focused studies including: the potential of bavituximab to shift the tumor microenvironment from immuno-suppressive in which tumors evade immune detection to a state of immune activation in which the immune system recognizes and fights the tumor; bavituximab’s potential to increase the number of activated CD8+ cells in the tumor, which stimulates PD-1 expression, potentially increasing the number of patients able to respond to PD-1 and PD-L1 targeting immunotherapies; and, results from several clinical and preclinical studies in a range of tumor types showing that bavituximab and bavituximab-like antibodies, in combination with conventional therapy, have consistently demonstrated estimated survival curves that plateau.

Data from preclinical studies presented at the 2015 ASCO (Free ASCO Whitepaper) annual meeting demonstrated the ability of the company’s PS-targeting antibodies to significantly increase the prevalence of tumor infiltrating CD8+ T-cells and immune-activating cytokines, while decreasing tumor-promoting macrophages and myeloid cells. These findings highlight the ability of the antibodies to enhance the anti-tumor effects of both chemotherapy and immune checkpoint inhibitors.

Avid Bioservices Highlights
Avid’s new manufacturing suite is fully constructed and the first internal pilot run is currently underway to verify all systems and equipment are properly functioning. Company plans to announce the launch of the new facility in the near term, allowing us to meet our internal manufacturing timelines as well as those of our third-party clients.

Contract manufacturing committed backlog reached $42 million from existing customers covering services to be completed in FY 2016 and into FY 2017.

Corporate Highlights
The European Patent Office (EPO) granted Patent Number 2,269,656, licensed to Peregrine titled "Selected Antibodies Binding to Aminophospholipids and their Use in Treatment, Such as Cancer." The patent covers bavituximab as a composition of matter and for use in therapy, such as for treating cancer including in combination with radiotherapy or chemotherapy, e.g., with docetaxel. This important patent expands upon the company’s intellectual property portfolio, which now numbers more than 140 worldwide issued patents and pending applications for the bavituximab oncology program.

Financial Results
Total revenues for the first quarter of FY 2016 were $9,671,000, compared to $5,496,000 for the same quarter of the prior fiscal year. The increase was primarily attributed to an increase in contract manufacturing revenue generated from Avid Bioservices.
Contract manufacturing revenue from Avid’s clinical and commercial biomanufacturing services provided to its third-party clients for the first quarter FY 2016 were $9,379,000, compared to $5,496,000 for the same quarter of the prior fiscal year. Peregrine expects third-party contract manufacturing revenue for FY 2016 to be between $30 and $35 million. In addition to providing biomanufacturing services to its third-party clients, Avid will continue to support the clinical and potential commercialization of bavituximab.

Total costs and expenses in the first quarter of FY 2016 were $23,425,000, compared to $18,667,000 in the first quarter of FY 2015. This increase was primarily attributable to current quarter increases in research and development expenses associated with the SUNRISE Phase III trial and increases in the cost of contract manufacturing associated with higher reported revenue. For the first quarter of FY 2016, research and development expenses were $13,918,000, compared to $10,201,000 for the first quarter of FY 2015. For the first quarter of FY 2016, cost of contract manufacturing was $4,608,000, compared to $3,583,000 for the first quarter of FY 2015.

Peregrine’s consolidated net loss attributable to common stockholders was $15,101,000, or $0.08 per share, for the first quarter of FY 2016, compared to a net loss attributable to common stockholders of $14,157,000, or $0.08 per share, for the same prior year quarter.

Peregrine reported $59,016,000 in cash and cash equivalents as of July 31, 2015 compared to $68,001,000 at fiscal year ended April 30, 2015.

More detailed financial information and analysis may be found in Peregrine’s Quarterly Report on Form 10-Q, which will be filed with the Securities and Exchange Commission today.

OncoSec Presents Advancements in Intratumoral Gene Electro-Transfer Devices for Immuno-Oncology

On September 9, 2015 OncoSec Medical Incorporated ("OncoSec") (NASDAQ: ONCS), a company developing DNA-based intratumoral cancer immunotherapies, reported recent advancements in the field of electroporation (EP) and the future of catheter-based devices to perform minimally invasive intratumoral immunotherapy treatment at the First World Congress on Electroporation and Pulsed Electric Fields in Biology, Medicine and Food & Environmental Technologies in Portoroz, Slovenia (Press release, OncoSec Medical, SEP 9, 2015, View Source [SID:1234507432]).

In a keynote presentation entitled: "Advances in Clinical Electroporation: Tissue Sensing, Feedback Control, and Catheter Technology," Robert H. Pierce, MD, Chief Scientific Officer, discussed OncoSec’s advances in intratumoral gene electro-transfer, using ‘smart’ tissue-sensing technology and the development of catheter-based electrodes, enabling treatment of deep and visceral tumors.

"We are excited to be presenting our engineering advances at the First World Congress," said Dr. Pierce. "The development of minimally-invasive electroporation devices capable of high-efficiency delivery of immunotherapeutic genes into tumors located anywhere in the body is critical to establishing intratumoral EP-mediated gene therapy as a standard therapeutic modality in immuno-oncology."

OncoSec’s New Catheter Electrode Technology

OncoSec’s new catheter-based electrodes are designed to be compatible with standard medical instrumentation, allowing access to deep and visceral tumors, where they are capable of anchoring to and treating the tumor using OncoSec’s proprietary technology. These all-in-one devices have the ability to inject a DNA-based agent, while deploying electrodes to perform electroporation in a single procedure. Moreover, these devices have an adjustable needle and electrode penetration depth allowing clinicians to treat tumors of varying dimensions to perform minimally invasive intratumoral immunotherapy.

Development of Tissue Sensing and Feedback Control

OncoSec is developing ‘smart’ electroporation technology capable of tissue sensing and real-time feedback control of electroporation pulse trains in order to attain optimal gene transfer and minimal electroporation-mediated tissue damage. Dr. Pierce added: "Taken together, these engineering advances can enable access and high-efficiency gene delivery to tumors throughout the body. This is key as we move forward in developing OncoSec’s pipeline of novel intratumoral therapies."

"Our partnership with Rev.1 Engineering and internal bioengineering expertise have allowed OncoSec to enhance our ImmunoPulse platform and position the Company as a leader in gene electro-transfer technologies in cancer immunotherapy," said Punit Dhillon, President and CEO of OncoSec. "We are also strengthening our intellectual property portfolio in the area of gene and drug delivery via electroporation to reach visceral tumors and enhance the uptake of therapeutic agents."

Licensing of University of South Florida Catheter Electrode Patent

OncoSec secured an exclusive license for a specific patented technology from the University of South Florida Research Foundation (USFRF). The patent provides a device and related methods to deliver molecules to cells that comprise any tissue. The patent includes a catheter-based electrode and methods to deliver molecules to cardiac tissue, blood vessels, other tissues/organs that can be accessed through a luminal tissue and luminal tissues. The device also functions as a non-catheter based electrode for performing the same functions. Financial terms of this agreement were not disclosed.

For more information about OncoSec and its technologies, please visit: www.oncosec.com.

OncoMed Pharmaceuticals Announces Presentation of Tarextumab Small Cell Lung Cancer Data at the 16th World Conference on Lung Cancer

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.

"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.