2015 Archived Content

Cambridge Healthtech Institute’s Second Annual
Rational Combination Cancer Immunotherapy
Designing and Implementing Strategies for Increasing the Efficacy of Cancer Immunotherapy by Combining Checkpoint Inhibitors and Biotherapeutics
August 25-26

The clinical and regulatory successes of the PD-1 and CTLA-4 checkpoint proteins are driving a resurgence of interest in immunotherapy as a mainstream form of cancer treatment, with numerous clinical studies exploring the application of these therapeutics in combinations with traditional and experimental agents.  CHI’s 2nd Annual Rational Combination Cancer Immunotherapy takes a forward-looking perspective on the design of drug products and treatment progressions that will build on the knowledge arising from these exploratory trials. The meeting will explore the scientific assumptions, patient diagnostic inputs and historical basis for different immunotherapy combinations – and consider new paradigms for the clinical studies that will evaluate these programs in the progression from research to commercialization. 

Day 1 | Day 2 | Download Brochure | Speaker Biographies
UD: Unpublished Data | CS: Case Study

Recommended Dinner Short Course*
Targeting the Cancer Mutanome
*Separate registration required


Polly-Matzinger11:15 PLENARY KEYNOTE Dangerous Thoughts on Immunotherapy

Polly C. Matzinger, Ph.D. Senior Investigator, Ghost Lab, Laboratory of Immunogenetics, NAID/NIH

What we think influences what we do. If we continue to view the immune system through the old fashioned self-non-self model, the likelihood of finding truly effective immunotherapies is vanishingly small, whether those therapies are for autoimmunity, cancer or transplantation. I will delineate the different predictions from the various models of immunity and show how they influence how we approach immunotherapy.

12:15 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:45 Session Break

1:30 Chairperson’s Opening Remarks

Omid HamidOmid Hamid, M.D., Director, Melanoma Program, Angeles Clinic and Research Institute


Llew Keltner, M.D., Ph.D., CEO, EPISTAT

An acute concern of both biotechs and KOLs in IO is getting access to anti-PD-1/PD-L1 from pharma for combination trials. The current state of combination IO trials will be reviewed. The different policies of pharma companies with clinical-stage/marketed anti-PD-1/anti- PD-L1 about access to their compounds for combination trials will be compared. Trial designs and indications that might have decent luck in getting the cooperation of these companies will be suggested.


2:20 Biomarkers in Melanoma – Right Patient: Right Trial

Omid HamidOmid Hamid, M.D., Director, Melanoma Program, Angeles Clinic and Research Institute

2:50 Sponsored Presentation (Opportunity Available)

3:05 Refreshment Break in the Exhibit Hall with Poster Viewing

Pramod Srivastava
3:35 Defining a True Tumor-Specific Epitope for Effective Cancer Immunotherapy

Pramod Srivastava, M.D., Ph.D., Professor, Immunology and Medicine, University of Connecticut School of Medicine; Director, Carole and Ray Neag Comprehensive Cancer Center

High-throughput genomics and bioinformatics have opened the floodgates for identification of neoepitopes of cancers. A vast majority of these are however ineffective in eliciting host-protective anti-tumor immune response. How does one identify the needle in this haystack?

4:05 Biomarkers to Support the Development and Clinical Application of Immunotherapy Combinations

Jelveh LamehJelveh Lameh, Ph.D., Executive Director, Head BioPharma Services Laboratory, Genoptix Medical Laboratory Inc., a Novartis Company

Biomarkers have successfully been applied to multiple aspects of cancer therapy. Up until now, biomarkers have been applied to various aspects of therapies that were targeted directly at the tumor cells. With the recent advances in immunotherapy, the rationale for combination therapies to circumvent resistance has emerged. Thus, application of biomarkers for such combination therapies is expected to improve patient outcomes.

4:35 Prognostic and Predictive Markers for Immunotherapy and Combination Therapy

Kathleen M. MahoneyKathleen M. Mahoney, M.D., Ph.D., Clinical Instructor, Beth Israel Deaconess Medical Center; Post-Doctoral Fellow, Dana Farber Cancer Institute

Tumor expression of PD-L1 has received much attention as a potential biomarker for PD-1/PD-L1 directed therapy. However it is an inappropriate exclusive biomarker, since “PD-L1 negative” tumors may respond to PD-1 pathway blockade. Emerging data suggests multivariate models including PD-L1 expression and the immune infiltrate within the tumor microenvironment may direct immunotherapy decisions. Incorporating the tumor’s mutational landscape, in addition to immunohistochemistry and gene expression signatures, may improve these platforms.

5:05 Welcome Reception in the Exhibit Hall with Poster Viewing

6:00 Dinner Short Course Registration*

Day 1 | Day 2 | Download Brochure | Speaker Biographies
UD: Unpublished Data | CS: Case Study


8:00 am Morning Coffee


8:25 Chairperson’s Opening Remarks

Hutchins JeffJeff T. Hutchins, Ph.D., Vice President, Preclinical Research, Peregrine Pharmaceuticals

Michael A. Postow
8:30 Immune Checkpoint Modulation: Rational Design of Combination Strategies

Michael A. Postow, M.D., Assistant Attending Physician, Melanoma and Immunotherapeutics Service, Memorial Sloan-Kettering Cancer Center

The immune system can be manipulated to enhance antitumor immunity. Efficacy has been demonstrated by approaches that block immune checkpoints, but not all patients benefit from treatment and improved outcomes are needed. Therapeutic approaches combining multiple immune checkpoint inhibitors with standard anticancer agents (radiotherapy, targeted therapy, and chemotherapy) are of great interest. Current approaches and a framework for the future will be discussed.

Jeff T. Hutchins
9:00 Expansion and Activation of T Cells via the Targeting of the Immunosuppressive Ligand Phosphatidylserine (PS): Combination Strategy with Conventional, Targeted, and Checkpoint Inhibitor Therapy

Jeff T. Hutchins, Ph.D., Vice President, Preclinical Research, Peregrine Pharmaceuticals

The underlying cause for the failure of current therapies is the persistent and multifocal immune suppression in the tumor microenvironment that drives the absence of pre-existing antitumor T cells. Bavituximab blocks PS-mediated immunosuppression (decreasing MDSCs) by reprograming immune cells in the tumor microenvironment to enhance anticancer activity. Pre-clinical, translational, and clinical results using bavituximab with conventional and immunotherapy combinations promotes a robust, anti-tumor T cell mediated response to enhance cancer therapy.

9:30 Distinct Immunologic Changes In Vivo Following Combination Versus Individual PD-1 or CTLA-4 Checkpoint Blockade in Human Cancer

Dhodapkar KavitaKavita Dhodapkar, MBBS, Associate Professor of Pediatrics, Yale School of Medicine

Combination therapy targeting PD1 and CTLA4 leads to remarkable anti-tumor effects and a distinct pattern of autoimmunity. We show that combination blockade leads to distinct changes in T cell and monocyte coding genes, alternatively-spliced transcripts, and non-coding RNAs compared to either anti-CTLA4 or anti-PD1 therapy alone. Our data suggests that each strategy serves as a unique immune-therapeutic. Improved understanding of pharmacodynamic effects may allow rational development of future immune-based combinations. 

10:00 Late-Breaking Presentation

10:15 Coffee Break in the Exhibit Hall with Poster Viewing

11:00 Cancer Vaccine/Immune Checkpoint Combinations

Marc MansourMarc Mansour, Ph.D., Chief Executive Officer, Immunovaccine, Canada

Combining T cell activating therapies with other immune modulating strategies targeting the tumor microenvironment hold a lot of promise for cancer therapy. Our data show that combining antigen directed T cell activation with cyclophosphamide as an immune modulator enhances systemic immunity and T cell activity in the tumor. The further addition of a checkpoint inhibitor causes additional changes in the tumor microenvironment leading to enhanced anti-tumor activity. The rationale for combining immunotherapies to manage advanced disease will be discussed.

11:30 The TAM Receptor Tyrosine Kinase Family and Their Potential to Modulate Macrophage and Dendritic Cell Function Create Opportunities to Combine with T Cell Checkpoint Drugs

Jerry McMahonJerry McMahon, Ph.D., President & CEO, Kolltan Pharmaceuticals

TAM receptor tyrosine kinases and their cognate ligands play a key role in immune homeostasis through signaling in macrophage and dendritic cells and regulating the adaptive immune response. Modulation of the activation of these receptors may up- or down-regulate immune homeostasis for the treatment of cancer and other diseases. Inhibition of Axl and MerTK are under investigation to potentiate the effectiveness of biologic agents that interfere with T cell checkpoints in tumor immunology.

12:00 pm Late-Breaking Presentation

12:30 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:55 Chairperson’s Remarks

Ravi MadanRavi Madan, M.D., Clinical Director, Genitourinary Malignancies Branch, National Cancer Institute

UD_Icon2:00 Enhanced Efficacy of IL-15-based ALT-803 Superagonist Complex in Combination with Immune Checkpoint Inhibitors

Alter SarahSarah Alter, Ph.D., Scientist and R&D Project Manager, Altor Bioscience

ALT-803 is an IL-15 superagonist:IL-15Rα-Fc complex with improved pharmacokinetics, biodistribution, and efficacy compared to native IL-15. It was shown that ALT-803 induces both innate effector-like and adaptive T cell antitumor activity, suggesting that ALT-803 complements the activity of checkpoint inhibitors to block tumor immune evasion. In murine models, ALT-803+anti-PD-L1+anti-CTLA-4 mAb treatment provided greater survival of tumor-bearing mice compared to treatment with vehicle or ALT-803 alone or the IL-15+anti-PD-L1+anti-CTLA-4 mAb combination.


David E. Hill
2:30 Interactome Networks and Human Disease: Potential Applications for Cancer Immunotherapy

David E. Hill, Ph.D., Associate Director, Center for Cancer Systems Biology (CCSB); Principal Scientist, Department of Cancer Biology, Dana-Farber Cancer Institute

Complex systems formed by interactions among genes and gene products underlie cellular functions. Basic concepts of network biology emphasize why cellular networks are important to consider. To generate the information necessary to address how complex networks relate to biology, we have developed at proteome scale an integrated approach for modeling protein-protein interaction networks. Our main questions are: How are interactome networks organized; how can we uncover features underlying this organization; and how are interactome networks modified in human disease, such as cancer?

Alexander Anderson
3:00 Phase i Trials in Melanoma: A Framework to Translate Preclinical Findings to the Clinic

Alexander Anderson, Ph.D., Chair, Integrated Mathematical Oncology Program, Moffitt Cancer Center

We present a computational framework to implement phase i trials (virtual/imaginary yet informed clinical trials) in cancer. Using an experimentally calibrated mathematical model, comprising a system of ordinary differential equations, we predict the dynamics of melanoma cells under different mono and combination therapies. We then implement a phase i trial in melanoma and show that we can readily capture observed heterogeneous clinical outcomes and predict optimal future clinical trial design.

3:30 Refreshment Break in the Exhibit Hall with Poster Viewing


4:15 Regulatory Challenges in Development of Novel Cancer Combinations

Elena SpanjaardElena Spanjaard, Ph.D., Director, Worldwide Research & Development, Regulatory Affairs, Pfizer

The growing demand for combination cancer therapies presents complex regulatory challenges that require modality-specific approaches. Current FDA guidance provides a framework for early development of investigational compounds intended for use in combination. Regulatory concepts that address development of novel biologic combinations, bifunctionals and antibody-drug conjugates will be reviewed, and key considerations for nonclinical and clinical phases of development will be highlighted for each modality.

4:45 Clinical Experience with Immune Combinations in Prostate Cancer

Ravi MadanRavi Madan, M.D., Clinical Director, Genitourinary Malignancies Branch, National Cancer Institute

There is strong rationale for immune-based combinations in the treatment of prostate cancer and clinical data is emerging. These combinations, which include anti-androgen therapies, radiation, chemotherapy and other immune-based treatments, have relevance across multiple tumor types. Perhaps most importantly, the potential for immune-based therapies to generate personalized anti-tumor immune responses is also being developed.

5:15 Close of Rational Combination Cancer Immunotherapy

Day 1 | Day 2 | Download Brochure | Speaker Biographies

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