Cambridge Healthtech Institute’s Third Annual 

Predictive Preclinical Models in Oncology 

Modeling for Targeted and Immune-Mediated Therapy Assessment

February 16-18, 2015 | Moscone North Convention Center | San Francisco, CA
Part of the 22nd Annual Molecular Medicine Tri-Conference

 

Predicting whether a potential new anticancer agent will be effective in patients remains a challenge. Despite tremendous progress in our understanding of cancer biology, the majority of novel anticancer therapies fail in Phase III clinical trials. This situation brings into question the quality of preclinical tumor models and predictability of preclinical studies in oncology. There is a critical need for models and approaches that allow to more effectively evaluate novel cancer therapeutics as well as to identify predictive biomarkers early in drug development. CHI’s Third Annual Predictive Preclinical Models in Oncology is designed to highlight the cutting-edge in vitro and in vivo preclinical tumor models and to facilitate a discussion about effective translational approaches in cancer research.


Day 1 | Day 2 | Day 3 | Plenary Session | Download Brochure 

MONDAY, FEBRUARY 16

10:30 am Conference Program Registration


ADVANCES IN TUMOR MODELING=ADVANCES IN CANCER DRUG DISCOVERY AND DEVELOPMENT

11:50 Chairperson’s Opening Remarks


12:00 pm Assessing the Predictive Value of Preclinical Cancer Models

Alexander Kamb, Ph.D., Senior Vice President, Discovery Research, Amgen

Cancer drugs work via two general mechanisms: cell-autonomous and non-cell-autonomous. Preclinical experimental models designed to test these mechanisms fall into two basic categories: in vitro (cell-based) and in vivo. In this presentation I consider the utility of these approaches in their various forms for oncology research.

12:30 Targeting Developmental Pathways in Cancer

Frederic de Sauvage, Ph.D., Vice President, Molecular Oncology, Genentech

Developmental pathways such as Wnt, Notch and Hedgehog play an important role in the development of a number of cancers. I will discuss the use of various mouse models of cancer to study the preclinical activity of pathway inhibitors and characterize potential mechanisms of innate or acquired resistance.

1:00 Session Break

1:15 Luncheon Presentation I: PDX Models for Improved Translational Research and Preclinical Prediction

Yan Yang, Director, Laboratory Operations, In Vivo Services, The Jackson Laboratory

James Keck, Senior Director, Clinical Lab & In Vivo Pharmacology Services, The Jackson Laboratory

Patient-derived xenograft (PDX) models can recapitulate patient tumor histopathology, mutational status, gene expression patterns, and drug response with remarkable fidelity. At The Jackson Laboratory, we have established a repository of more than 350 well-characterized PDX tumor models and are working with leading cancer centers on translational studies at the forefront on personalized medicine. We will discuss recent progress toward the use of PDX models for predictive oncology treatment.

1:45 Luncheon Presentation II (Sponsorship Opportunity Available)

2:15 Session Break


MODELLING AND RESEARCHING BRAIN CANCER

2:30 Chairperson’s Remarks

2:40 Preclinical Trials in Mouse Models of Brain Tumors

Eric C. Holland, M.D., Ph.D., Senior Vice President, Director,Human Biology, Solid Tumor Translational Research, Nancy and Buster Alvord Brain Tumor Center, Fred Hutchinson Cancer Research Center, University of Washington

We have been using genetically and histologically accurate models of gliomas for preclinical trials. The models are driven by PDGF that appears to be the initiator for most human GBMs. These models respond to the standard of care for gliomas such as radiation and temozolomide in a similar manner as humans. We have used these models to better understand the biology of therapeutic response as well as optimize and enhance radiation efficacy.

3:10 Intertwined Regulation of Angiogenesis and Immunemodulation in Cancer Progression and Resistance

Gabriele Bergers, Ph.D., Professor of Neurological Surgery, Neill H. and Linda S. Brownstein Endowed Chair in Brain Tumor Research, Principal Investigator, Brain Tumor Research Center, University of California, San Francisco

The current evidence suggests that several adaptive mechanisms mediate evasive resistance to anti-angiogenic therapies, of which those facilitating a proangiogenic relapse include upregulation of alternative proangiogenic factors and tumor infiltration of various innate immune cells. All of these cell types display angiogenic and immune suppressive functions in tumors supporting the notion that angiogenesis and immune suppression appear to go hand-in hand. Here, we will discuss how antiangiogenic therapy affects immune modulation and how in turn, immune cells affect antiangiogenic therapy.

3:40 PANEL DISCUSSION: Addressing the Key Challenges in Preclinical Modeling

Moderator: Norman Greenberg, Ph.D.

Panelists: Speakers of the Day

  • Choosing the appropriate model for our studies
  • Modeling the genetic and phenotypic heterogeneity seen in the clinic
  • Overcoming drug resistance
  • Testing combination strategies
  • Identifying translational biomarkers from model data

4:10 Using Populations of Targeted PDX Models to Support Preclinical Trials of Oncology Therapeutics

Thomas Broudy, Ph.D., CSO, Molecular Response

The depth of the Molecular Response tumor bank (144k specimens, 76 diagnoses) enables broad-based PDX studies in patient populations meeting specific criteria, such as: mutational status, failed therapy or metastatic lesions.  By approximating the clinical setting in a preclinical context, we help partners establish confident developmental approaches across oncology programs.

4:25 Sponsored Presentation (Opportunity Available)

4:40 Break and Transition to Plenary Session

5:00 PLENARY SESSION

6:00 Grand Opening Reception in the Exhibit Hall with Poster Viewing

7:30 Close of Day


Day 1 | Day 2 | Day 3 | Plenary Session | Download Brochure 

TUESDAY, FEBRUARY 17

7:00 am Registration and Morning Coffee

8:00 PLENARY SESSION

9:00 Refreshment Break in the Exhibit Hall with Poster Viewing


TRANSLATIONAL APPROACHES IN CANCER IMMUNOTHERAPY DEVELOPMENT

10:05 Chairperson’s Remarks

James F. Smothers, Ph.D., Senior Director & Head, Discovery, Immuno-Oncology & Combinations DPU, Oncology R&D, GlaxoSmithKline

10:15 Biomarkers in Cancer Immunotherapy

Ira Mellman, M.D., Vice President, Cancer Immunology, Genentech

Recent advances in cancer immunotherapy differ from other developments in oncology therapeutics in several respects. Not only have immunotherapies proved remarkably promising, but also the underlying science promises to be largely driven by findings in the clinic. Thus, both patient selection and the discovery of new therapeutic opportunities will be dependent on the ability to identify, collect, and understand biomarkers and immunobiology of patient response and lack of response.

10:45 Strategies for Clinical Development of Cancer Immunotherapy

Roy Baynes, M.D., Senior Vice President Global Clinical Development, Merck

The discovery that BRAF is a driver oncogene in cancer, and complementary improvements in our understanding of the immune system have resulted in new targeted and immunetherapies for metastatic melanoma. Targeted therapies achieve impressive clinical results in carefully selected patients but the development of resistance seems inevitable in most cases. Conversely, immune-checkpoints inhibitors can achieve long-term remission and cures, but in a smaller proportion of patients, and biomarkers to predict which patients will respond are not available.

11:15 Translational Approaches for the Development of Intratumoral Immunotherapies

Robert Pierce, M.D., CMO, OncoSec Medical, Inc.

Intratumoral therapies are capable of reversing local immunosuppressive mechanisms and driving systemic anti-tumor immune responses. Given the safety and potential systemic efficacy of this approach, Intratumoral therapies will likely play a growing role in future combination immunotherapy regimens. The pros and cons of current syngeneic mouse models will be addressed with particular emphasis on unique aspects of intratumoral therapies.

11:45 Preclinical Validation of Immunotherapies and Combination Strategies for Cancer

James Smothers, Ph.D., Senior Director, Head, Discovery, Immuno-Oncology & Combinations DPU, Oncology R&D, GlaxoSmithKline

Recent clinical strategies to modulate T cell checkpoint pathways have demonstrated significant patient benefit in melanoma, renal cell carcinoma and non-small cell lung cancer indications. Clinical successes with immuno-oncology medicines greatly depend upon animal disease model studies and other pre-clinical rationale for their development. Translational data coupled with pre-clinical results can further bridge understanding of what patient populations might gain the most benefit from an immuno-oncology experimental medicine alone or in combination with another agent.

12:15 pm Session Break

12:25 Luncheon Presentations (Sponsorship Opportunities Available) or Lunch on Your Own

1:25 Refreshment Break in the Exhibit Hall with Poster Viewing


UNFOLDING CANCER IMMUNOTHERAPY MECHANISMS

2:00 Chairperson's Remarks 

Alan L. Epstein, M.D., Ph.D., Department of Pathology, USC Keck School of Medicine, Los Angeles

2:10 Inflammation and Cancer: Immune Cells as Targets For Anti-Cancer Therapy

Lisa M. Coussens, Ph.D., Professor and Chair, Director, Basic Research, Department of Cell & Developmental Biology, Knight Cancer Institute, Oregon Health & Sciences University

The concept that leukocytes are components of solid tumors is not new; however, their functional involvement as promoting forces in tumor progression has only recently been appreciated. We are interested in understanding the molecular mechanisms that regulate leukocyte recruitment into neoplastic tissue, subsequent regulation those leukocytes exert on evolving cancer cells, and how malignant cells in turn respond to cytotoxic therapies.

2:40 Criteria for Identifying Responses to Cancer Immunotherapy

Alan L. Epstein, M.D., Ph.D., Department of Pathology, USC Keck School of Medicine, Los Angeles

Immune profiling of tumor biopsies at the time of diagnosis can be used to determine what mechanisms are induced by tumors to defeat host immunity. Specifically, we have determined that evaluation of the immunogenicity of tumors and the identification of immunosuppressive cells and molecules provide critical information. In this way, immune signatures can be used to enhance clinical trial results and reduce the time to approval for new agents.

3:10 How to Unleash Anti-Tumor Immunity by Modulating the PI3K Pathway

Khaled Ali, Ph.D., Senior Scientist, Amgen Oncology

The phosphoinosidite-3-OH kinase (PI3K) pathway is a key therapeutic target activated in most tumors. Inhibitors against the p110δ isoform of PI3K have shown remarkable therapeutic efficacy in some human leukemias. As p110δ is primarily expressed in leukocytes, drugs against p110δ have not been considered for the treatment of solid tumors. Recently we have demonstrated that p110δ inactivation in mice protects against a broad range of cancers, including non-hematological solid tumors. p110δ inactivation in regulatory T cells unleashes CD8 cytotoxic T cells and induces tumor regression.

3:40 Sponsored Presentations (Opportunities Available)

4:10 Mardi Gras Celebration in the Exhibit Hall with Poster Viewing

5:00 Breakout Discussions in the Exhibit Hall

This interactive session provides attendees an opportunity to choose a specific discussion group to join. Each group has a moderator to ensure focused discussions around key issues within the topic. This format allows participants to meet potential collaborators, share examples from their work, vet ideas with peers, and be part of a group problem-solving endeavor. The discussions provide an informal exchange of ideas and are not meant to be a corporate or specific product discussion.

Criteria for Identifying Response to Cancer Immunotherapy 

Moderator: Alan L. Epstein, M.D., Ph.D., Department of Pathology, USC Keck School of Medicine, Los Angeles

Topics to be discussed:

  • Evaluation of the immunogenicity of tumors
  • Immune profiling of tumor biopsies
  • Role of suppressor cell populations

Modeling for Preclinical Assessment of Combination Therapy

Moderator: Khaled Ali, Ph.D., Senior Scientist, Amgen Oncology


Expanding the Utility of PDX Platforms

Neal Goodwin, Ph.D., Director, Corporate Research Development, Champions Oncology

  • Champions established PDX resource for conducting virtual clinical trials
  • Champions matched patient PDX-directed clinical trials programs
  • Champions humanization PDX models for immunocheckpoint testing

6:00 Close of Day


Day 1 | Day 2 | Day 3 | Plenary Session | Download Brochure 

WEDNESDAY, FEBRUARY 18

7:00 am Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee

8:00 PLENARY SESSION PANEL

9:45 Refreshment Break and Poster Competition Winner Announced in the Exhibit Hall


PDX MODELS TO INFORM CLINICAL TRIALS

10:35 Chairperson’s Remarks

Neal Goodwin, Ph.D., Vice President, Corporate Research and Development, Champions Oncology

10:45 Towards Personalized Medicine: Companion Therapeutics in the I-SPY 2 TRIAL

Laura J. van ‘t Veer, Ph.D., Professor of Laboratory Medicine, University of California San Francisco; Leader, Breast Oncology Program; Associate Director, Applied Genomics, UCSF Helen Diller Family Comprehensive Cancer Center; Principal Investigator, Bay Area Breast Cancer SPORE; Angela and Shu Kai Chan Endowed Chair in Cancer Research

Cancer therapeutics are nowadays targeted to inhibit the activated networks. The multitude of choices is effectively evaluated in the neo-adjuvant therapeutic setting where drugs are given before surgery and direct tumor response can be monitored by imaging. Accompaniment by comprehensive molecular diagnostics allows one to find the right drug for the right patient. The I-SPY 2 breast cancer trial maximizes the neoadjuvant approach by adaptively assigning patients to the treatment arm where their tumors biology is showing the most effective response.

11:15 Optimizing Clinical Trial Designs by PDX Integration

Philip C. Mack, Ph.D., Associate Adjunct Professor, Internal Medicine, Hematology and Oncology, University of California Davis Medical Center

Compared to cell lines and GEMMs, Patient-derived Xenografts (PDXs) are a superior representation of the molecular complexity and natural evolution of patient tumors. In collaboration with The Jackson Laboratory (JAX), we have developed an extensive, well-characterized resource of over 60 NSCLC PDX models. Models retain the mutational characteristics, heterogeneity and histology of the donor tumor. Integration of PDX modeling into clinical trials provides an opportunity to optimize personalized therapeutic strategies that has not been previously available.

 Champions Oncology11:45 Patient Derived Xenograft Clinical Trial Program  

Neal Goodwin, Ph.D., Vice President, Corporate Research and Development, Champions Oncology

A PDX clinical program to guide patient treatment has engrafted >750 patient specimens with a 70% patient tumor take rate and a >80% correlative treatment accuracy in completed clinical tests. This program has been expanded to support predictive clinical trials for breast, sarcoma, and lung cancers in partnership with clinical trial centers and cooperative trial groups. Ultimately, this program will include matched patient translational studies across numerous patient models for Phase II trial patient stratification.

12:15 pm Session Break

12:25 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

1:00 Refreshment Break in the Exhibit Hall and Last Chance for Poster Viewing


TRANSLATIONAL APPROACHES TO CHILDHOOD CANCER

1:40 Chairperson's Remarks 

Peter Houghton, Ph.D., Director, Greehey Children's Cancer Research Institute, University of Texas Health Science Center, San Antonio

1:50 Translational Genomics of Pediatric Cancers to Identify Novel Biomarkers, Drivers and Therapeutic Targets

Javed Khan, M.D., Genetics Branch Head, Oncogenomics SectionDeputy Branch Chief, Center for Cancer Research, National Cancer Institute

Recently there has been an explosion of information related to the cancer genome. I will describe the use of high throughput technologies such as next-generation sequencing, siRNA and compounds screening to identify novel biomarkers, drivers and therapeuric targets. I will summarize some of the key discoveries made, focusing my comments on neuroblastoma, rhabdomyosarcoma and Ewing's sarcoma. Finally I will describe the use of genomics for precision therapy trials for children with refractory or relapsed cancers.

2:20 Preclinical Childhood Cancer Models for Developing Molecularly Targeted Therapies

Peter Houghton, Ph.D., Director, Greehey Children's Cancer Research Institute, University of Texas Health Science Center, San Antonio 

The Pediatric Preclinical Testing Program (PPTP) supported through the National Cancer Institute, has developed in excess of 150 patient derived tumor xenograft models (PDX). These models have been characterized by expression profiling, SNP analysis and exome sequencing. The primary screen utilizes 49 xenograft models to identify agents that have broadspectrum or tumor-type selective activity. Examples of the predictive value of expression profiles or sequence data for identification of active agents will be discussed.

2:50 The Institutes for Molecular Medicine at Phoenix Children’s Hospital to Address the Unmet Need: Slow Progress in Pediatric Drug Development

Nazneen Aziz, Ph.D., Senior Vice President & Chief Research Officer, Phoenix Children’s Hospital

More effective therapies are unavailable in pediatric cancer, in stark contrast to the rapid introduction of targeted therapies in adult cancer that are revolutionizing the treatment of adults with cancer. PCH’s Molecular Medicine Program will focus on utilizing genomic methodologies to better understand mechanisms of disease and to stratify patient populations, with the ultimate goal of improving clinical care and outcomes. The program will support a dynamic interplay between the clinic, the laboratory, and pharmaceutical companies focusing on real-time translation of scientific knowledge and patient data to identify the best possible treatment of patients.

3:20 PANEL DISCUSSION: Childhood Cancer Research: Specific Features and Advances

Moderator: Peter Houghton, Ph.D., Director, Center for Childhood Cancer, The Research Institute, Nationwide Children’s Hospital

Panelists: Speakers of the Session

3:50 Refreshment Break


INNOVATIVE IN VITRO AND IN VIVO MODELING

4:00 Chairperson’s Remarks

4:0 Chairperson's Remarks

Philip Martin, D.V.M., Veterinary Pathologist, Center for Advanced Preclinical Research (CAPR), Frederick National Laboratory for Cancer Research & Leidos Biomedical Research, Inc.

4:10 Using 3-D Organoid Model to Target Stem Cells in Colorectal Cancer

Felipe de Sousa e Melo, Postdoctoral Research Fellow, Molecular Oncology, Genentech

Cancer stem cells have been reported in various cancers, including in colorectal cancer (CRC). The functional relevance of cancer stemness for tumor growth is still poorly characterized. We have devised a 3-D organoid culture model to define the functional properties of stem cells in CRC. Using this approach, we found that Lgr5 identifies a subpopulation of cancer cells endowed with stem-like properties. Strategies to eradicate this population will be discussed.

4:40 Validation of a Tumor Antigen also Expressed on Subsets of Activated Lymphocytes as a T Cell Engager BiTE® Therapy Target

Olivier P. Nolan-Stevaux, Ph.D., Senior Scientist, Department of Oncology, Amgen, Inc.

BiTE® therapeutics are small single chain antibodies harboring two binding moieties: one directed at a tumor antigen and one directed at the CD3e protein, which triggers T cell mediated cytotoxicity against targeted cancer cells. We have developed BiTE® molecules that recognize a promising cell surface tumor antigen that is also expressed by subsets of T and B cells, and we will present the behavior of these BiTE® molecules in various assays and pre-clinical models.

5:10 Preclinical Models of Human Cancer at the Center for Advanced Preclinical Research (CAPR): Quantitative Methods for Assaying Drug Efficacy and Resistance

Philip Martin, D.V.M., Veterinary Pathologist, Center for Advanced Preclinical Research (CAPR), Frederick National Laboratory for Cancer Research & Leidos Biomedical Research, Inc.

At CAPR we have developed/optimized several important preclinical cancer models including: pancreatic, lung, melanoma, glioblastoma, and ovarian. This talk will give a brief description of each model including its development as a genetically engineered mouse (GEM) model and its eventual evolution into an immunocompetent transplantation model, and its advantages/disadvantages in modeling the human disease. In addition, the talk will focus on the quantitative methods that we use at CAPR to assay host immune response, drug efficacy, as well as the development of drug resistance.

5:40 Close of Conference Program



Day 1 | Day 2 | Day 3 | Plenary Session | Download Brochure 

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