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Charles River Laboratories Updates Tumor Model Compendium

On December 4, 2019 Charles River Laboratories International, Inc. (NYSE: CRL) reported updates to its online Tumor Model Compendium. Charles River’s cancer model database provides access to a comprehensive collection of well-established tumor models for early-stage oncology research (Press release, Charles River Laboratories, DEC 4, 2019, View Source [SID1234551935]).

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This update adds 79 new patient-derived xenografts (PDX), 10 new cell line-derived xenografts (CDX), and 36 new cell line (CL) models for several cancer types including: anal, colon, lung and renal cancer as well as leukemia and melanoma. Additionally, the update provides an increased depth of data for both whole exome sequencing (WES) and gene expression, with greater bioinformatics coverage:

71 new WES data sets, increasing whole exome data to 90 percent of models
92 new RNA-Seq data sets, increasing gene expression data to 87 percent of models
Charles River’s Compendium includes tumor models from a wide range of tumor subtypes for both in vivo and in vitro oncology research, including patient-derived xenografts (PDXs), cell line-derived xenografts (CDX), and syngeneic models.

This resource allows researchers to easily identify the most appropriate tumor models, leading to a more targeted study design from the start, saving time and money on the path to the clinic. The Compendium, when combined with Charles River’s robust portfolio of oncology services and scientific background, provides a highly translational platform for developing safe, effective oncology therapeutics.

Expansion of Oncology Portfolio
Charles River recently launched in vivo tumor microdialysis to support cancer research. Microdialysis is a uniquely sensitive and powerful method of sampling the tumor microenvironment of research models. With microdialysis, researchers are able to gather actionable data on the mechanism of action and perform more efficient decision making. Traditionally applied to neuroscience research, utilizing microdialysis in tumor models provides an excellent approach to model the pharmacokinetics of a given therapeutic compound.

Charles River has also developed two new research models specifically for the study of Graft vs Host Disease (GvHD). GvHD and other pharmacodynamic models can act as screening tools to evaluate the ability of immunoregulatory drugs to modulate disease progression, providing valuable information to progress the best version of a drug past preclinical testing.

Additionally, Charles River recently launched an expansion of its PDX portfolio in North America. Benefiting from over 30 years of experience, Charles River’s global PDX capabilities provide clients with the scientific guidance necessary to progress novel cancer therapeutics. To learn more about Charles River’s oncology research capabilities, visit www.criver.com.

Approved Quotes

"In oncology, we recognize the importance of identifying a model that will most closely mimic human disease, increasing translation from preclinical research to the clinic. An increased depth of data and additional model types provide an improved resource for making those critical decisions." – Birgit Girshick, Corporate Executive Vice President, Discovery & Safety Assessment, Biologics Testing Solutions, and Avian Vaccine Services at Charles River
"The application of microdialysis in oncology research provides a unique opportunity for researchers to detect and quantify multiple immunomodulators and oncometabolites from freely moving, tumor-bearing models. This insight into target engagement and mechanism of action aids faster progression into the clinic." – Arash Rassoulpour, PhD, Executive Director at Charles River
"Stem cell transplantation, while offering many anti-cancer benefits, has a high risk of complications due to the introduction of donor cells into a patient’s immune system. GvHD models provide a valuable tool to study the biology of this disease and improve success rates of stem cell transplantation as a cancer treatment." – Chassidy Hall, Site Director, Oncology Center of Excellence at Charles River

Bioasis Appoints Consultant Chief Medical Officer and Nominates Medical Oncology Advisory Board

On December 4, 2019 BIOASIS TECHNOLOGIES INC. (OTCQB:BIOAF; TSX.V:BTI), ), a pre-clinical, research-stage biopharmaceutical company developing its proprietary xB3 platform technology for the delivery of therapeutics across the blood-brain barrier (the "BBB") and the treatment of central nervous system ("CNS") disorders in areas of high unmet medical need, including brain cancers and neurodegenerative diseases, reported the creation of the Medical Oncology Advisory Board and the appointments of Dr. John DeGroot M.D., Dr. Hope Rugo M.D. and Dr. Javier Cortés M.D. PhD (Press release, biOasis, DEC 4, 2019, View Source [SID1234551934]). The goals of this board will be to guide the clinical strategy and design of the xB3-001 clinical program for the treatment of HER2+ breast cancer and brain metastases. The Medical Oncology Advisory Board will be chaired by José Iglesias, MD, who has been appointed consultant Chief Medical Officer for Bioasis Technologies Inc.

Dr. José Iglesias, Chairperson of the Advisory Board in his role of consultant Chief Medical Officer is a biopharmaceutical industry veteran with 30 years of executive experience in all phases of oncology clinical drug development covering the areas of solid tumor oncology, immuno-oncology and translational medicine. His career includes senior positions at Eli Lilly, Amgen, Abraxis Bioscience, Celgene, Bionomics, Biothera, Apobiologix and Boston Biomedical. Dr. Iglesias is author or co-author of more than 60 peer-reviewed publications with over 6,000 literature citations and an active member of ASCO (Free ASCO Whitepaper), ESMO (Free ESMO Whitepaper) and AACR (Free AACR Whitepaper). He graduated from the University of Montevideo, Uruguay, and received additional training at the Weizmann Institute of Science (Rehovot, Israel), Duke University Medical Center (Durham, NC) and the University of Toronto.

"I am delighted to welcome José to the Bioasis team, strengthening our oncology development expertise at a critical time as we progress our lead program xB3-001 for the treatment of HER2+ breast cancer and brain metastases. I am also extremely pleased to welcome John, Hope and Javier to the Medical Oncology Advisory Board. Each member is a leader in their field with proven track records of excellence in clinical practice and clinical drug development in the areas of breast cancer and CNS oncology." Deborah Rathjen added, Ph.D., Executive Chair of Bioasis. "We look forward to continuing to benefit from the strength of the collective experience of our medical board as we advance our xB3 programs toward the clinic."

Dr. José Iglesias commented, "Treatment of HER2+ breast cancer that has metastasized to the brain remains a significant challenge. To date, xB³-001 has demonstrated highly encouraging preclinical results, and I am excited to be working with Dr. Rathjen and the Bioasis team to continue to advance this class-leading technology."

Dr. John de Groot is a Professor, and Chairman ad interim, in the Department of Neuro-Oncology at The University of Texas MD Anderson Cancer Center. He is an expert in the fields of glioma angiogenesis and molecularly targeted therapy. Dr. de Groot has served as the principal investigator (PI) or co-investigator on multiple funded National Cancer Institute, foundation, and industry-sponsored grants. He is the principal investigator of numerous clinical trials involving novel agents being tested in patients with glioblastoma and is a leader of MD Anderson’s Glioblastoma Moon Shot. Dr. de Groot has over 112 peer reviewed articles. He is or has been a peer reviewer for 23 scientific journals, both national & international, and is on four editorial review boards. He completed his medical education at The University of Texas Medical Branch at Galveston, and pursued internship and residency at The Johns Hopkins School of Medicine.

Dr. Hope S. Rugo is Professor of Medicine at the University of California San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center, where she is also the director of Breast Oncology and Clinical Trials Education. She is a principal investigator of multiple clinical trials focusing on combining novel targeted therapeutics with standard treatment to improve the treatment of both early and late stage breast cancer and improving safety with targeted agents and has published widely in this area with over 200 peer reviewed articles. Dr. Rugo is an active member of the Translational Breast Cancer Research Consortium (TBCRC), a principal investigator of several TBCRC trials and is the co-chair of the Triple Negative Working Group. She is a member of the Breast Committee for the Alliance cooperative group, and is an associate editor for the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting educational book. Dr. Rugo graduated from the University of Pennsylvania School of Medicine. She completed a residency in internal medicine followed by a fellowship in hematology and oncology at UCSF as well as a research fellowship at Stanford University.

From June 2003 to July 2015, Dr.Cortés worked in the Department of Medical Oncology at the Hospital Vall d’Hebron, Barcelona, where he has been Coordinator of the Teaching and Training Programme for Residents in Oncology and Senior Specialist in the Area of Breast Cancer with a special interest in new drug development. Dr. Cortés was the Head of the Breast Cancer Program and the Melanoma Unit from July 2006 to August 2015. From September 2015 to October 2018, he has been Head of the Breast Cancer and Gynecological tumors at Ramon y Cajal University Hospital in Madrid. He is Clinical Investigator of the Breast Cancer Research Program at Vall d’Hebron Institute of Oncology, and Head of Breast Cancer Program, IOB Institute of Oncology, Madrid and Barcelona, Spain. Dr Cortés is the author of more than 240 publications, with a focus on breast tumors and new drugs, and more than 500 communications at multiple conferences. He actively participates in the development of numerous national and international clinical investigations. Dr Cortés received a degree in Medicine and Surgery from the Universidad Autónoma de Madrid with continued studies at the University of Navarra, specializing in Medical Oncology at the Clínica Universitaria de Navarra. In addition to his medical specialties, he has two masters’ degree in Medical Direction and Clinical Management from the Universidad Nacional de Educación a Distancia (UNED) and Research Methodology in Health Sciences from the Universidad Autónoma de Barcelona as well as a degree in Statistics in Health Sciences from the same university.

ImmunityBio Granted FDA Breakthrough Therapy Designation for N-803 IL-15 Superagonist in Non-Muscle Invasive Bladder Cancer

On December 4, 2019 ImmunityBio, a privately held immunotherapy company, reported that it has received Breakthrough Therapy Designation (BTD) from the U.S. Food and Drug Administration (FDA) for its interleukin-15 (IL-15) agonist complex, N-803, in combination with Bacillus Calmette-Guerin (BCG), for the treatment of patients with BCG-unresponsive non-muscle invasive bladder carcinoma in situ (CIS) (Press release, ImmunityBio, DEC 4, 2019, View Source [SID1234551933]).

This grant of Breakthrough Designation follows on the receipt of Fast Track Designation from the U.S. Food and Drug Administration for N-803 in 2017. The FDA’s Breakthrough Therapy Designation program is designed to expedite the development and review of drugs intended to treat serious conditions and fill unmet medical needs.1 The FDA published guidance in February 2018 to address BCG unresponsive non-muscle invasive bladder cancer (NMIBC), stating that the goal of therapy in patients with BCG-unresponsive NMIBC is to avoid cystectomy.

"We are pleased that the FDA has granted Breakthrough Therapy Designation to N-803 in combination with BCG for the treatment of patients with Non-Muscle Invasive Bladder Cancer with CIS," said Dr. Patrick Soon-Shiong, Chairman and CEO of ImmunityBio. "We look forward to accelerating our work on N-803 to bring greater hope to the thousands of people living with the serious consequences of bladder cancer and to address the unmet need to avoid surgical removal of the bladder in these high-risk patients. Patients who fail current standard of care and who have high risk carcinoma in situ of the bladder are left with a difficult choice of having their bladder removed, a procedure fraught with a clinically significant mortality and morbidity rates. The potential opportunity to avoid this procedure and change the course of this disease with the addition of N-803 is immensely gratifying," he said.

"The favorable safety profile and initial efficacy results from our phase 1 study strongly suggest we may be able to improve the treatment for a disease that has not had non-surgical treatment options for over 30 years," said ImmunityBio Chief Medical Officer, Dr. John Lee.

ImmunityBio’s N-803, an IL-15 Superagonist

The cytokine interleukin-15 (IL-15) plays a crucial role in the immune system by affecting the development, maintenance, and function of the natural killer (NK) and T cells. N-803 is a novel IL-15 superagonist complex consisting of an IL-15 mutant (IL-15N72D) bound to an IL-15 receptor α/IgG1 Fc fusion protein. N-803 has improved pharmacokinetic properties, longer persistence in lymphoid tissues and enhanced anti-tumor activity compared to native, non-complexed IL-15 in vivo.

N-803 is currently being evaluated for adult patients in two clinical NMIBC trials. QUILT 2.005 is investigating use of N-803 in combination with BCG for patients with BCG-naïve NMIBC; QUILT 3.032 is studying N-803 in combination with BCG in patients with BCG-unresponsive NMIBC.

The Urgent, Unmet Need to Treat NMIBC and Avoid Cystectomy

Bladder cancer has a high incidence worldwide, with 199,922 deaths and an estimated 549,393 new cases in 2018.2 In the United States, bladder cancer is the fourth most commonly diagnosed solid malignancy in men and the twelfth for women; The American Cancer Society estimates 80,470 new cases and 17,670 deaths in 2019.3 Bladder cancers are described based on how far they have invaded into the wall of the bladder. NMIBC occurs when the cancer has not grown into the main muscle layer of the bladder. Approximately 75-85% of all newly diagnosed cases of bladder cancer are non-muscle invasive bladder cancer (NMIBC).4

For the last 30 years, BCG immunotherapy has been the standard for treating NMIBC. However, disease recurrence and progression rates remain unacceptably high. Standard of care recommendations for these patients include lifetime invasive surveillance and rapid treatment of recurrences, creating a substantial financial burden and drastic impact on quality of life. Of those patients who experience recurrence, approximately 30% will progress and succumb to their disease over a 15-year period, and another 50% will undergo radical cystectomy of the bladder in an attempt to control their disease.5

For high-risk NMIBC patients who are BCG-unresponsive with persistent or recurrent disease, treatment guidelines recommend a surgical procedure called radical cystectomy, a surgery to remove the entire bladder that may require removal of other surrounding organs. In men, removal of the prostate may be necessary, and in women, surgeons may also remove the uterus, fallopian tubes, ovaries and cervix, and occasionally a portion of the vagina. Despite the advent of minimally invasive procedures and robotic techniques, the 90-day mortality and morbidity rates in patients who undergo cystectomy remain unacceptably high at 5.1-8.1% and 28-64%, respectively.6 Based on this urgent need, FDA published guidance in February 2018 to address BCG unresponsive non-muscle invasive bladder cancer (NMIBC), stating that the goal of therapy in patients with BCG-unresponsive NMIBC is to avoid cystectomy.

Personal Genome Diagnostics Receives Investigational Device Exemption Approval from the FDA to Support Merck’s Precision Oncology Trial

On December 4, 2019 Personal Genome Diagnostics Inc. (PGDx), a leader in cancer genomics, reported that it received Investigational Device Exemption (IDE) approval from the U.S. Food and Drug Administration (FDA) for the use of the company’s elio tissue complete assay in a Merck trial of pembrolizumab-based combination therapy (Press release, Personal Genome Diagnostics, DEC 4, 2019, View Source [SID1234551931]). The PGDx elio assay will be used during the trial to analyze genomic markers to direct patient enrollment and stratification.

"We’re pleased with the FDA’s decision to approve PGDx’s elio tissue complete assay for this trial, as it validates the robustness of the test and reinforces the role of diagnostic biomarkers in investigating treatment strategies for patients living with cancer," said Doug Ward, Chief Executive Officer at PGDx. "Further, Merck’s selection of this assay for use in their trials underscores its value and performance in ongoing oncology research."

The PGDx elio tissue complete panel is a 500+ gene test for somatic alterations that detects single nucleotide variants (SNVs), small insertion/deletions, amplifications, rearrangements, microsatellite instability (MSI) and tumor mutation burden. PGDx provides genomic solutions from biomarker discovery to companion diagnostic development through its CAP/CLIA certified laboratory and is developing a portfolio of regulated tissue-based and liquid biopsy genomic products to enable local next-generation sequencing (NGS) testing in laboratories worldwide.

Foundation Medicine Expands Indication for FoundationOne®CDx as a Companion Diagnostic for Piqray® (alpelisib)

On December 4, 2019 Foundation Medicine, Inc. reported it has received approval from the U.S. Food and Drug Administration (FDA) for FoundationOneCDx to be used as a companion diagnostic for Piqray (alpelisib) in combination with fulvestrant for the treatment of postmenopausal women, and men, with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA mutated, advanced or metastatic breast cancer following progression on or after an endocrine-based regimen (Press release, Foundation Medicine, DEC 4, 2019, View Source [SID1234551930]). FoundationOne CDx is the first and only FDA-approved broad comprehensive genomic profiling (CGP) test for all solid tumors, including breast cancer, that incorporates multiple companion diagnostics.

"Foundation Medicine is proud to achieve another FDA approval for FoundationOne CDx as a companion diagnostic for Piqray for the treatment of metastatic breast cancer with a PIK3CA mutation," stated Brian Alexander, M.D., M.P.H. Foundation Medicine’s Chief Medical Officer. "The advancements we are seeing in the treatment of breast cancer underscore the importance of harnessing genomic insights to enable personalized medicine. Taking a comprehensive and validated approach to genomic testing is critical for patients with metastatic breast cancer to help physicians determine a treatment roadmap upfront that may include FDA-approved targeted therapies like Piqray."

In May of 2019, Novartis announced that the FDA approved Piqray (alpelisib) in combination with fulvestrant for the treatment of postmenopausal women, and men, with HR+/HER2-, PIK3CA mutated, advanced or metastatic breast cancer following progression on or after an endocrine-based regimen metastatic breast cancer with a PIK3CA mutation following progression on or after an endocrine-based regimen. PIK3CA is the most commonly mutated gene in HR+/HER2- breast cancer; approximately 40% of patients living with HR+/HER2- breast cancer have this mutation1. Professional guidelines were updated in September of 2019 to recommend assessment for PIK3CA mutations as part of the workup of HR+/HER2- advanced or metastatic breast cancer.

Piqray is the first and only treatment specifically for patients with a PIK3CA mutation in HR+/HER2- advanced breast cancer. Foundation Medicine and Novartis have an ongoing collaboration to support the development of companion diagnostics for the Novartis oncology portfolio.

Foundation Medicine will also be presenting new data at this year’s San Antonio Breast Cancer Symposium (SABCS) highlighting the utility of comprehensive genomic profiling in cancer care, including research on PIK3CA, as well as emerging biomarkers in breast cancer.