Cambridge Healthtech Institute’s Third Annual 

Predictive Preclinical Models in Oncology 

Mastering Translational Oncology with Predictive Models and Novel In-Silico Approaches

March 7-9, 2016 | Moscone North Convention Center | San Francisco, CA
Part of the 23rd International Molecular Medicine Tri-Conference


Despite tremendous progress in our understanding of cancer biology, the majority of novel anticancer therapies fail in clinical trials, which indicates failure of conventional translational approaches. A major challenge in the development of novel anticancer agents is the design and interpretation of first-in-man trials. The key study design elements such as schedule, escalation strategy, targeted patient population, etc. rely heavily on preclinical (usually in vivo) data. This situation brings into question the predictability of preclinical tumor models as well as the method to analyze and translate the results of preclinical studies. In that regard, better in vivo models, coupled with careful translational PK/PD modeling hold the potential to significantly increase the value of preclinical results. Better predictive modeling would hopefully permit more effective evaluation of novel cancer therapeutics, (for example, cancer immunotherapeutics), as well as the more rational design of potent anticancer drug combinations. Cambridge Healthtech Institute’s Fourth Annual Predictive Pre-Clinical Models in Oncology is designed to highlight cutting edge advances in in vivo, in vitro and in silico modeling and to facilitate a discussion about effective translational approaches in cancer research.

Final Agenda

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Monday, March 7

10:30 am Conference Program Registration Open


11:50 Chairperson’s Opening Remarks

Arijit Chakravarty, Ph.D., Director, Modeling and Simulation (DMPK), Takeda Pharmaceuticals International Co.

12:00 pm Utilizing Large Scale in vivo Screening with PTX Models Predicts Drug Response in Cancer Patients

Juliet Williams, Ph.D., Head, Oncology Drug Discovery, Novartis Institute for Biomedical Research

Profiling candidate therapeutics using a limited set of cancer models during preclinical development hinders accurate predictions of clinical efficacy. We established ~1000 patient-derived tumor xenograft models, with comprehensive genomic landscape analyses. Subsequently, we performed population-based in vivo compound screens using a 1x1x1 experimental design to assess the response and resistance of 70 treatments across six indications. We demonstrate both the reproducibility and clinical translatability of this approach and additionally demonstrate examples of PTX superiority over cell-based xenografts in predicting clinical response.

12:30 Visualizing and Interacting with Clinical/Molecular Cancer Big Datasets

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 are developing computational tools that allow interactive visualization of large datasets of clinical and molecular cancer patients. These tools are able to analyze any tumor type, but are initially created around the TCGA Glioma data as a demonstration dataset. Using this data, groups of structurally similar tumors can be identified, and the clinical outcomes of these groups can be determined. This tool can be used to identify more homogenous populations of patients for clinical trials.

1:00 Session Break

Jackson Laboratory1:15 Luncheon Presentation I: Patient-Derived Tumor Xenografts in Humanized NSG-SGM3 Mice: A New Immuno-Oncology Platform

James G. Keck, Ph.D., Senior Director, Clinical Lab & in vivo Pharmacology Services, The Jackson Laboratory

Humanized mice engrafted with tumors enable in vivo investigation of the interactions between the human immune system and human cancer. We have recently found that humanized NOD-scid IL2Rγnull (NSG) mice bearing patient-derived xenografts (PDX) allow efficacy studies of check-point inhibitors. Next-generation NSG strains include triple transgenic NSG mice expressing human cytokines KITLG, CSF2, and IL-3 (NSG-SGM3). Here we provide a direct comparison of check-point inhibitors evaluation in NSG and NSG-SGM3 mice engrafted with CD34+ human hematopoietic progenitor cells (HPCs) from the same donor and implanted with PDX tumors.

1:45 Luncheon Presentation II (Sponsorship Opportunity Available)

2:15 Session Break


2:30 Chairperson’s Remarks

Arijit Chakravarty, Ph.D., Director, Modeling and Simulation (DMPK), Takeda Pharmaceuticals International Co.

» 2:40 KEYNOTE PRESENTATION: The Mechanistic Basis of Cancer Immunotherapy

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

3:10 Epigenetic Priming for Immunotherapy in Breast Cancer

Pamela N. Munster, M.D., Professor of Medicine; Program Leader, Development Therapeutics; Director, Early Phase Clinical Trials’ Program, Helen Diller Cancer Center, University of California, San Francisco

A break down in immune tumor surveillance plays a crucial role in the development of metastatic cancer. Targeting the programmed death receptor (PD-1) and its ligand (PD-L1) have been major breakthroughs. In breast cancers however, particularly in hormone-driven breast cancer, immune responses are often absent. In reverse-translating clinical findings from the patient to preclinical models we show that epigenetic modulation leads to epigenetic immune priming and enhancement of immune response.

3:40 The Human as the Animal Model: Preclinical and Intra-Clinical Translation in Oncology

Arijit Chakravarty, Ph.D., Director, Modeling and Simulation (DMPK), Takeda Pharmaceuticals International Co.

The challenges of Oncology drug development are legion, and differ subtly from those of other therapeutic areas. On the one hand, disease tissue from patients is readily available for study. On the other hand, the real translational unknown is the toxicity profile. In this presentation, I will make a (contrarian) case for improving the modeling of clinical toxicity data and increasing the reliance on preclinical xenograft efficacy data.

Champions Oncology4:10 Advanced PDX Tumor Biology Platforms for Drug Advancement

Neal Goodwin, Vice President, Corporate Research & Development,
Champions Oncology

Collections of PDX models have tested investigational compounds for efficacy predictions, and PDX-based platforms can be used with spontaneous mouse models and GEMMs to discover new therapeutic targets, resistance mechanisms, and biomarker signatures of response. There are, however, limits to their use in clinical trial simulation. Coupled-PDX trials are being advanced - clinical trials are combined with companion PDX studies to help guide follow-on trial design. Matched patient-PDX-directed trials will see PDX models used to screen for experimental drug efficacy, with patients enrolled onto trials based on their PDX drug response.

4:40 Refreshment Break and Transition to Plenary Session

5:00 Plenary Keynote Session

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

7:30 Close of Day

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Tuesday, March 8

7:00 am Registration Open and Morning Coffee

8:00 Plenary Keynote Session

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


10:05 Chairperson’s Remarks

Chad May, Ph.D., Director, Oncology Research Unit, Pfizer

10:15 Preclinical Tumor Models for Evaluating Bispecific Redirected T-Cell Therapeutics

Chad May, Ph.D., Director, Oncology Research Unit, Pfizer

Strong evidence exists supporting the important role T-cells play in the immune response against tumors. Still, the ability to initiate tumor specific immune responses remains a challenge. We have developed a bispecific protein engineered with enhanced pharmacokinetic properties to extend in vivo half-life, and designed to engage and activate endogenous polyclonal T-cell populations via the CD3 complex in the presence of tumors expressing target antigens.

10:45 Assessing ENPP3 as a Renal Cancer Target for Bi-Specific T-Cell Engager (BiTE®) Therapy

Olivier Nolan-Stevaux, Ph.D., Senior Scientist, Oncology Research, Amgen, Inc.

BiTE® therapeutics are single chain antibody constructs 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. Here, we will present the development of BiTE® Antibody Constructs recognizing the ENPP3 protein, a target prominently expressed in clear cell Renal Cell Carcinoma, and the assessment of these molecules in vitro and in preclinical models.

11:15 Improved Systemic Responses through the Rational Combination of Immunotherapy with Radiation

James W. Welsh, M.D., Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center

The immune-modulating effects of radiation therapy have recently gained considerable interest and there have been multiple reports of synergy between radiation and immunotherapy. However, additional preclinical studies are needed to demonstrate the antigen-specific nature of radiation induced immune responses and elucidate potential mechanisms of synergy with immunotherapy. Here we demonstrate the ability of stereotactic radiotherapy to induce endogenous antigen-specific immune responses when combined with anti-PD-1 checkpoint blockade immunotherapy.

11:45 An Evolving Molecular Taxonomy of Melanoma

Boris C. Bastian, M.D., Ph.D., Professor of Dermatology and Pathology, Gerson and Barbara Bass Bakar Distinguished Professor in Cancer Research, University of California, San Francisco

Melanocytic neoplasms constitute a phenotypically diverse group of tumors that encompass a broad range of clinically, histopathologically, and molecularly diverse lesions. We will discuss their differences in terms of their cell of origin, pattern of genetic alterations, role of UV radiation, mutational process that shape their genomes and genetic evolution.

12:15 pm Session Break

12:25 Luncheon Presentation I to be Announced


12:55 Luncheon Presentation II (Sponsorship Opportunity Available)

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


2:00 Chairperson’s Remarks

Bruce R. Zetter, Ph.D., Charles Nowiszewski Professor of Cancer Biology, Department of Surgery, Harvard Medical School

2:10 Markers, Mechanisms and Treatment of Resistant Cancer

Bruce R. Zetter, Ph.D., Charles Nowiszewski Professor of Cancer Biology, Department of Surgery, Harvard Medical School

Focusing on resistance to taxanes, we have uncovered novel mechanisms of chemoresistance that depend on upregulation of cell surface Prohibitin 1 (PHB1). XIAP levels are upregulated in several human cancers and correlate with decreased survival in patients with non-small cell lung cancer (NSCLC). Our recent results demonstrate that PHB1 promotes resistance to apoptosis by stabilizing the X-linked inhibitor of apoptosis, XIAP. We further find that systemic delivery of nanoparticles carrying siRNA to PHB1 results in restoration of taxane sensitivity in preclinical models of NSCLC.

2:40 Mechanistic Basis of Palbociclib Resistance and Combinatorial Activity in ER+ Breast Non-Breast Cancer Indications

Stephen Dann, Ph.D., Principal Scientist, Pfizer Oncology Research Unit

Phosphorylation of the retinoblastoma protein (Rb) by cyclin-dependent kinases 4 and 6 (CDK4/6) is a critical cell cycle checkpoint. Human malignancies that depend on CDK4/6 activity for proliferation and survival are sensitive to the CDK4/6 inhibitor palbociclib (IbranceTM). In ER+ breast cancer models palbociclib and estrogen antagonists combine for anti-proliferative activity, cellular senescence and prolonged durability of response. Data will be presented on the molecular basis of combination benefit with palbociclib in ER+ breast and other oncology indications.

3:10 PANEL DISCUSSION: Modeling and Researching Cancer Drug Resistance

Moderator: Bruce R. Zetter, Ph.D., Charles Nowiszewski Professor of Cancer Biology, Department of Surgery, Harvard Medical School

What is the best way to study resistance? What are the challenges in translating promising therapeutic interventions to a clinical setting? These seemingly distinct questions are deeply intertwined. This panel discussion will cover these and other practical topics at the interface of basic science and practical applications in cancer.

3:40 A Complete Workflow for Isolating Pure Tumor Cell Populations from Primary Tissue for Improved Downstream Analyses

Olaf Hardt, Ph.D., Senior Project Manager, Research & Development, Miltenyi Biotec

Both tumor and non-tumor cells exist within the tumor environment. Reliable analyses of tumor cells therefore requires pure cell populations, as contaminating non-tumor cells can affect the results of downstream assays. Depletion of mouse cells from xenograft tumors or stromal cells from human or mouse tumors is simple with our tumor cell isolation workflow.

3:55 Sponsored Presentation (Opportunity Available)

4:10 St. Patrick’s Day Celebration in the Exhibit Hall with Poster Viewing

5:00 Breakout Discussions in the Exhibit Hall 

These interactive discussion groups are open to all attendees, speakers, sponsors, & exhibitors. Participants choose a specific breakout 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.

Modeling for Preclinical Assessment of Combination Therapy
Olivier Nolan-Stevaux, Ph.D., Senior Scientist, Oncology Research, Amgen, Inc.
• Are in vitro assays useful in predicting clinically efficacious immune therapy combinations?
• Are current syngeneic mouse models adequate to test immune therapy combinations? What are the alternatives?
• Can we predict the toxicity of individual or combined immune therapies using preclinical models?
• Are Cynomolgus studies providing clinically relevant toxicity information?

Reverse Translation and Epigenetic Priming in Immuno-Oncology
Pamela N. Munster, M.D., Professor of Medicine; Program Leader, Development Therapeutics; Director, Early Phase Clinical Trials’ Program, Helen Diller Cancer Center, University of California, San Francisco
• How predictive are so call immunocompetent mouse models?
• Is human the best model for cancer immunotherapy?
• Is it possible to skip preclinical assessment all together?
• Logistics of information exchange between clinical and preclinical scientists

6:00 Close of Day

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Wednesday, March 9

7:00 am Registration Open

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

8:00 Plenary Keynote Session Panel

10:00 Refreshment Break and Poster Competition Winner Announced in the Exhibit Hall


10:50 Chairperson’s Remarks

Anderson Clark, Ph.D., Director, in vivo Pharmacology, Oncology, EMD Serono Research & Development

11:00 Integration of PDX Modeling into Clinical Trials: Biological, Clinical and Statistical Perspectives

Joint Presentation: David Gandara, M.D., Professor of Medicine, Division of Hematology/Oncology, University of California, Davis School of Medicine; Director, Thoracic Oncology Program, Senior Advisor to the Director, UC Davis Comprehensive Cancer Center; Chair, Lung Committee, Southwest Oncology Group (SWOG)

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

Mary Redman, Ph.D., Lead Statistician, Lung Cancer Committee Southwest Oncology Group, Lead Statistician, Lung Map Trial, Fred Hutchinson Cancer Research Center

12:00 pm Statistical Analysis of PDX Studies and Preclinical Phase-II-Like Trials (PP2T) at EMD Serono

Anderson Clark, Ph.D., Director, in vivo Pharmacology, Oncology, EMD Serono Research & Development

At EMD Serono, data from PDX (patient-derived xenograft) models of cancer are used to make clinical decisions for Phase II. In increasing the predictive value of these animal models, we have addressed questions about what constitutes a preclinical response in relationship to clinical RECIST criteria and what the proper statistical analyses of these models would be, and these outcomes will be presented.

12:30 Session Break

Surrogen12:40 Luncheon Presentation to be Announced

1:10 Refreshment Break in the Exhibit Hall and Last Chance for Poster Viewing


1:50 Chairperson’s Remarks

Byron C. Hann, M.D., Ph.D., Associate Researcher, Manager of Preclinical Therapeutics Core, UCSF Helen Diller Family Comprehensive Cancer Center

2:00 The Critical Role of Extracellular Matrix and Microenvironment in Metastasis and Dormancy

Mina J. Bissell, Ph.D., Distinguished Scientist, Life Sciences Division, Lawrence Berkeley National Laboratory

I will discuss why and how we developed, and use, 3-dimensional models of normal mammary gland and mammary tumors from both mice and humans to understand breast cancer, and will present recent work, shedding light on why tissue and organ architecture should become also a parameter in cancer research, and how architecture can regulate tissue-specificity as well as the plasticity of tumors. I will also discuss newer and more complex models we have developed to understand metastasis and dormancy and a screen that has allowed us to discover a new class of ‘oncogenes’ in the EGFR/PI3 Kinase.

2:30 Cell Line Genomics in Drug Discovery

Christiaan Klijn, Ph.D., Computational Biology, Genentech

Tumor-derived cell lines have served as vital models to advance our understanding of oncogene function and therapeutic responses. Understanding cell line genomics is critical to the effective and accurate use of cell lines in preclinical studies. I will describe our effort to map the transcriptome of more than 600 cell lines and various preclinical applications of this data.

3:00 Engineering the Genome to Investigate Disease Mechanisms

Randall Platt, Biological Engineering, MIT, Laboratory of Feng Zhang

The ability to sequence and edit DNA is fundamental to understanding the role of genetic elements in biological and disease processes. The RNA-guided endonuclease, CRISPR-Cas9, is widely being developed to not only simplify and expand genome editing applications but also reduce the cost and speed at which model organisms can be generated. This opens up exciting new avenues of research for a broad range of disease modeling applications.

3:30 Sponsored Presentation (Opportunity Available)

4:00 Session Break


4:10 Chairperson’s Remarks

Byron C. Hann, M.D., Ph.D., Associate Researcher, Manager of Preclinical Therapeutics Core, UCSF Helen Diller Family Comprehensive Cancer Center

4:15 Co-Clinical Trials of Targeted Therapies in Colorectal Cancer Patients and Patient Derived Xenografts

Joint Presentation: Chloe E. Atreya M.D., Ph.D., Assistant Clinical Professor, Gastrointestinal Oncology Program, University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center

Byron C. Hann, M.D., Ph.D., Associate Researcher, Manager of Preclinical Therapeutics Core, UCSF Helen Diller Family Comprehensive Cancer Center

Patient-derived xenograft (PDX) models share molecular and phenotypic similarity to patient cancer tissue and are presumed to have superior predictive value as a preclinical model. High rates of engraftment, success using needle biopsy starting material, and rapid growth make colorectal cancer (CRC) an ideal model to test this hypothesis. We compare PDX and clinical response to targeted therapeutics, and demonstrate concordance. We conduct co-clinical trials in CRC patients and PDX and aim to use response in PDX to direct selection of experimental agents for CRC patients.

5:15 A Humanized Ossicle-Niche Xenotransplantation Model with Improved Hematopoietic Engraftment

Andreas Reinisch, M.D., Ph.D., Institute for Stem Cell Biology and Regenerative Medicine (ISCBRM), Stanford University

Current xenotransplantation models do not recapitulate human bone marrow (BM) microenvironment components and exhibit limited engraftment of many human hematopoietic malignancies. We developed a xenotransplantation model bearing subcutaneous humanized accessible BM microenvironments formed by in situ differentiation of BM-derived mesenchymal stromal cells. In these humanized microenvironments, we detected extensive engraftment of diverse primary acute myeloid leukemia samples at levels much greater than in unmanipulated mice allowing for the identification of leukemia-initiating cells

5:45 Close of Conference Program

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