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Lilly and Merck Expand Immuno-Oncology Collaboration Adding Abemaciclib and KEYTRUDA® (pembrolizumab) Combination Trial

On December 10, 2015 Eli Lilly and Company (NYSE: LLY) and Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported another immuno-oncology collaboration that will evaluate abemaciclib (LY2835219), Lilly’s cyclin-dependent kinase (CDK) 4 and 6 inhibitor, and Merck’s KEYTRUDA (pembrolizumab) in a Phase I study across multiple tumor types. Based on the Phase I trial results, the collaboration has the potential to progress to Phase II trials in patients who have been diagnosed with either metastatic breast cancer or non-small cell lung cancer (NSCLC) (Press release, Merck & Co, DEC 10, 2015, View Source [SID:1234508522]).

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Lilly is the sponsor of the Phase I study, and of any subsequent Phase II studies, per the terms of the agreement. Enrollment is scheduled to begin in early 2016. Financial details of the collaboration were not disclosed.

Lilly’s abemaciclib is a cell cycle inhibitor, designed to block the growth of cancer cells by specifically inhibiting CDK4 and CDK6. Pembrolizumab is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. Pembrolizumab blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes, which may affect both tumor cells and healthy cells.

"With our active Phase III program underway for abemaciclib in both metastatic breast cancer and non-small cell lung cancer, we are committed to uncovering every opportunity to help these patients – and this includes exploring abemaciclib in combination with immunotherapy," said Richard Gaynor, M.D., senior vice president, product development and medical affairs for Lilly Oncology. "We’re encouraged by our productive immuno-oncology collaborations with Merck, through its affiliates, and coming together for another clinical trial is a natural evolution of our scientific collaboration."

"We look forward to continuing our collaboration with Lilly on this combination study with KEYTRUDA and abemaciclib," said Eric Rubin, M.D., vice president and therapeutic area head, oncology early-stage development, Merck Research Laboratories. "Strategic collaborations such as this one reinforce the commitment we have to bringing new combination treatments to the forefront for people with cancer."

NOTES TO EDITORS

About Abemaciclib

Cyclin-dependent kinases play a key role in regulating cell cycle progression. In many cancers, uncontrolled cell growth arises from a loss of control in regulating the cell cycle due to increased signaling from CDK4 and CDK6. Lilly’s abemaciclib (LY2835219) is a cell cycle inhibitor, designed to block the growth of cancer cells by specifically inhibiting CDK4 and CDK6, and in cell-free enzymatic assays has been shown to be most active against Cyclin D1/CDK4. Results from preclinical and early-stage clinical studies support the further evaluation of abemaciclib for the treatment of human cancers – including breast cancer and lung cancer – in which aberrant CDK4 and CDK6 pathways enhance cancer cell growth.

Abemaciclib is in Phase III development with two trials in HR+ breast cancer patients, as well as a Phase III trial in lung cancer.

ArQule and Daiichi Sankyo Announce Completion of Accrual in METIV-HCC Phase 3 Trial of Tivantinib for Second-Line Hepatocellular Carcinoma

On December 10, 2015 ArQule, Inc. (Nasdaq: ARQL) and Daiichi Sankyo, Inc. reported that the phase 3 METIV-HCC trial for tivantinib in second-line hepatocellular carcinoma (HCC) has completed accrual (Press release, ArQule, DEC 10, 2015, View Source [SID:1234508521]).

In addition, the planned interim analysis, which is triggered when 60 percent of events occur, is expected to take place early in the second quarter of 2016.

The METIV-HCC trial is a biomarker-driven, double-blind, placebo-controlled, pivotal phase 3 trial where patients are randomized 2:1 comparing tivantinib to best supportive care. The trial is conducted under a Special Protocol Assessment and has accrued more than 300 HCC patients with MET-high tumors only, as determined by an immunohistochemistry test. The trial is being conducted in western countries by Daiichi Sankyo and ArQule with a primary endpoint of overall survival. The planned interim analysis for Data Monitoring Committee (DMC) review was designed with an early stop for superiority.

"We are pleased to have fully accrued the METIV-HCC trial prior to year-end," said Brian Schwartz, M.D., Head of Research and Development and Chief Medical Officer at ArQule. "HCC is a disease with high unmet need and with no approved therapy for second-line treatment. It has been very encouraging to see a growing body of evidence supporting the phase 3 clinical evaluation of tivantinib in MET-high populations through a recent presentation at the International Liver Cancer Association conference."

"We would like to thank all the patients, investigators and clinical sites for partnering with us to achieve this important milestone," said Mahmoud Ghazzi, M.D., Ph.D, President and Global Head of Development for Daiichi Sankyo. "The completion of planned patient enrollment into METIV-HCC is an important step forward in the development of a potential new targeted treatment for patients with advanced HCC, who currently have limited options."

About Hepatocellular Carcinoma (HCC)
Liver cancer is the sixth most common cancer globally with 782,000 new cases in 2012 and is the second most common cause of cancer-related death with 745,000 deaths in 2012.
HCC accounts for about 90 percent of primary liver cancers. 2 Cirrhosis, chronic hepatitis B and C and smoking are recognized worldwide as factors increasing the risk of HCC.

About MET and Tivantinib (ARQ 197)
Tivantinib is an orally administered, selective inhibitor of MET, a receptor tyrosine kinase, which is currently in phase 2 and phase 3 clinical trials. In healthy adult cells, MET can be present in normal levels to support natural cellular function, but in cancer cells, MET can be inappropriately and continuously activated. When abnormally activated, MET plays multiple roles in aspects of human cancer, including cancer cell growth, survival, angiogenesis, invasion and metastasis. The activation of certain cell signaling pathways, including MET, has also been associated with the development of resistance to anti-EGFR (epidermal growth
factor receptor) antibodies such as cetuximab and panitumumab.

Pre-clinical data have demonstrated that tivantinib inhibits MET activation in a range of human tumor cell lines and shows anti-tumor activity against several human tumor xenografts. In clinical trials to date, treatment with tivantinib has been generally well tolerated
and has shown clinical activity in a number of tumors studied. Tivantinib has not yet been approved for any indication in any country.

In December 2008, ArQule and Daiichi Sankyo signed a license, co-development and cocommercialization agreement for tivantinib in the U.S., Europe, South America and the rest of the world, excluding Japan, China (including Hong Kong), South Korea and Taiwan. In November 2015, ArQule exercised its co-commercialization option for tivantinib in the U.S. A co-commercialization agreement is expected to be finalized in the first quarter of 2016.

Independent Data Monitoring Committee Recommends Continuation of ADAPT Phase 3 Clinical Trial of AGS-003 for Metastatic Renal Cell Carcinoma Following Second Planned Interim Analysis

On December 10, 2015 Argos Therapeutics Inc. (Nasdaq:ARGS) ("Argos"), an immuno-oncology company focused on the development and commercialization of fully individualized immunotherapies for the treatment of cancer based on the Arcelis technology platform, reported its independent data monitoring committee (IDMC) has recommended the continuation of the company’s pivotal phase 3 ADAPT clinical trial of AGS-003 for the treatment of metastatic renal cell carcinoma (mRCC) based on results of the committee’s second planned interim data analysis (Press release, Argos Therapeutics, DEC 10, 2015, View Source [SID:1234508520]).

"The ADAPT phase 3 trial to evaluate AGS-003 in front line mRCC, the largest global trial ever performed in newly diagnosed, unfavorable risk mRCC patients, continues to progress nicely," said Dr. Figlin, the Steven Spielberg Family chair in hematology oncology, professor of medicine and biomedical sciences at the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute and the principal investigator for the ADAPT trial. "We anticipate that we are approaching the mid-point for the expected number of events and look forward to the next interim review of the trial data in approximately six months."

AGS-003 is a fully individualized immunotherapy that captures mutated and variant antigens that are specific to each patient’s tumor and is designed to induce an immune response targeting that patient’s tumor antigens. In an open-label phase 2 study, treatment with AGS-003 plus sunitinib yielded a median overall survival of more than 30 months in newly diagnosed, unfavorable (intermediate and poor) risk mRCC patients. The randomized phase 3 ADAPT trial evaluating AGS-003 plus standard targeted therapy enrolled a total of 462 mRCC patients and has a primary endpoint of overall survival. AGS-003 is Argos’ most advanced Arcelis-based product candidate.

"We are excited by the IDMC’s recommendation to continue with the trial," said Jeffrey D. Abbey, president and chief executive officer of Argos. "This is an important step for the ADAPT trial and for the clinical development of AGS-003."

Conference Call and Webcast Details

Argos executive management will host a conference call with Dr. Figlin beginning at 5:00pm EST on Thursday, December 10, 2015 to discuss the IDMC recommendation to continue the trial, and to answer questions.

To participate by telephone, please dial (855) 433-0930 (Domestic) or (484) 756-4271 (International). The conference ID number is 4042406. A live and archived audio webcast can be accessed through the Investors section of the Company’s website at www.argostherapeutics.com. The archived webcast will remain available on the Company’s website for 12 months following the call.

About the Arcelis Technology Platform

Arcelis is a fully individualized immunotherapy technology that captures mutated and variant antigens that are specific to each patient’s disease. It is designed to overcome immunosuppression by producing a durable memory T-cell response without adjuvants that may be associated with toxicity. The technology is potentially applicable to a wide range of different cancers, and is designed to overcome many of the manufacturing and commercialization challenges that have impeded other personalized cancer immunotherapies. The Arcelis process uses only a small tumor or blood sample and the patient’s own dendritic cells, which are optimized from cells collected by a single leukapheresis procedure. The proprietary process uses RNA isolated from the patient’s disease sample to program dendritic cells to target disease specific antigens. The activated, antigen-loaded dendritic cells are then formulated into the patient’s plasma and administered via intradermal injection.

Neon Therapeutics Enters License Agreement with the Broad Institute, Dana-Farber Cancer Institute and Massachusetts General Hospital

On December 9, 2015 Neon Therapeutics, an immuno-oncology company developing neoantigen-based therapeutic vaccines and T cell therapies to treat cancer, reported that the company has entered into a license agreement with the Broad Institute, Dana-Farber Cancer Institute and Massachusetts General Hospital for technology to be utilized in Neon Therapeutics’ pipeline (Press release, Neon Therapeutics, DEC 9, 2015, View Source [SID1234517520]).

The work of Neon Therapeutics co-founders Catherine J. Wu, M.D., at the Broad Institute and Dana-Farber Cancer Institute, Nir Hacohen, Ph.D., at the Broad Institute and Massachusetts General Hospital, and Ed Fritsch, Ph.D., at the Broad Institute and Dana-Farber Cancer Institute, led to the development of a personalized neoantigen vaccine, which is the foundation for Neon Therapeutics’ proprietary lead compound, NEO-PV-01. The project was originated and led by the Broad Institute and was philanthropically funded in part by the Blavatnik Family Foundation. Dana-Farber Cancer Institute is currently enrolling two investigator-initiated trials with additional trials planned. Neon Therapeutics will build upon this research and initiate a company-sponsored clinical trial in 2016.

"Neon Therapeutics’ approach was borne out of years of research focused on developing novel cancer immunotherapies based on unique mutations present in the tumor DNA of each patient," said Cary Pfeffer, M.D., interim chief executive officer of Neon Therapeutics. "We are privileged to license technology from The Broad Institute, Dana-Farber Cancer Institute and Massachusetts General Hospital, each a world-leading cancer research institution, to leverage this excellent science to develop innovative neoantigen-based therapies."

Multiple Scientific Presentations at the San Antonio Breast Cancer Symposium Highlight the Clinical Utility of the Myriad myRisk(TM) Hereditary Cancer Gene Panel Test

On December 9, 2015 Myriad Genetics, Inc. (NASDAQ:MYGN), a leader in molecular diagnostics and personalized medicine, reported it will highlight three scientific presentations related to its myRisk Hereditary Cancer test at the 2015 San Antonio Breast Cancer Symposium (SABCS) in San Antonio, Texas (Press release, Myriad Genetics, DEC 9, 2015, View Source [SID:1234508518]). Data include results from studies that advance the understanding of hereditary cancer testing using multi-gene panels to evaluate patients at risk for or diagnosed with breast cancer.

"Our collaborators will present data at SABCS this year that show multi-gene panel testing with myRisk Hereditary Cancer provides clinically significant results that drive appropriate changes in patient care," said Johnathan Lancaster, M.D., Ph.D., chief medical officer, Myriad Genetic Laboratories. "Importantly, there are new data that demonstrate the positive perceptions from patients after they receive a multi-gene test result. Furthermore, as we expand our testing to broader gene panels and share scientific outcomes from our research collaborations, important new questions are being asked that will expand our thinking about exactly which patients should be tested for hereditary cancer."

Details about the featured myRisk Hereditary Cancer presentations at SABCS are below. Follow Myriad on Twitter via @MyriadGenetics and stay informed about symposium news and updates by using the hashtag #SABCS15.

myRisk Hereditary Cancer Poster Presentations

Title: Interim analysis of multiplex gene panel testing for inherited susceptibility to breast cancer.
Date: Friday, Dec. 11, 2015: 5:00 to 7:00 p.m. CT.
Location: Poster Discussion PD7-01.
Presenter: Dr. Gregory Idos, Stanford University Cancer Institute.

This multi-center prospective study was designed to analyze data from 2,000 patients undergoing cancer-risk assessment using the myRisk Hereditary Cancer 25-gene panel test. The objective was to determine the benefits of multi-gene panel testing versus traditional genetic testing. The interim analysis of the first 332 patients tested found that 11 percent were positive for a deleterious mutation. Among participants testing negative for BRCA1 and BRCA2 mutations, the myRisk test identified deleterious mutations in 14 patients, representing a 61 percent increase over BRCA testing alone and prompting clinically appropriate risk reduction recommendations and enhanced cancer surveillance. These findings demonstrate the ability of the myRisk Hereditary Cancer test to identify a subset of patients with deleterious mutations who historically would have been missed by traditional genetic testing for BRCA1/2 alone, and who could receive appropriate medical management as a result.

Title: The patient experience in a prospective trial of multiple-gene panel testing for cancer risk.
Date: Thursday, Dec.10, 2015: 7:30 to 9:00 a.m. CT.
Location: Poster P2-09-07.
Presenter: Dr. Allison Kurian, Stanford University Cancer Institute

In this study, 2,000 diverse patients at risk for hereditary breast/ovarian cancer syndrome were evaluated to determine the patient experience following genetic testing with the myRisk Hereditary Cancer test. Patients were surveyed at entry and three months after testing using the Multidimensional Impact of Cancer Risk Assessment (MICRA) scale. An interim analysis of the first 332 patients found that 87 percent said they did not regret learning about the results and 81 percent wanted all their genetic test results for all 25 genes tested. Although the study is ongoing, these interim results suggest there is no evidence of an increase in cancer- or testing-related distress/uncertainty after patients received their test results.

Title: Predisposing germline mutations in an unselected academic breast cancer (BC) cohort.
Date: Wednesday, Dec. 9, 2015: 5:00 to 7:00 p.m. CT.
Location: Poster P1-08-07.
Presenter: Dr. Judy Garber, Dana-Farber Cancer Institute

In this study, 456 patients newly diagnosed with breast cancer were evaluated for mutations in 25 cancer genes using the myRisk Hereditary Cancer test. The results show that 11 percent of the patients in a single academic institution had a germline mutation in a breast cancer predisposition gene. Approximately 7 percent were in BRCA1/2 genes and 4 percent were in other cancer genes. Of the 49 women with deleterious mutations associated with breast cancer, 21 (43 percent) were diagnosed after age 45. This finding suggests that patients diagnosed with breast cancer at older ages may benefit from genetic testing with the myRisk Hereditary Cancer gene panel test.

For more information about these presentations, please visit the SABCS website at View Source

About Myriad myRisk Hereditary Cancer Testing

The Myriad myRisk Hereditary Cancer test uses next-generation sequencing technology to evaluate 25 clinically significant genes associated with eight hereditary cancer sites including: breast, colon, ovarian, endometrial, pancreatic, prostate and gastric cancers and melanoma. For more information visit: View Source