Lung Cancer: Advances in Current Treatment Modalities and Patient Classification

Lung Cancer: Advances in Current Treatment Modalities and Patient Classification

Tuesday, March 25, 2014

The New York Academy of Sciences

Presented By

Presented by the Biochemical Pharmacology Discussion Group at the New York Academy of Sciences

 

Lung cancer is one of the most common and deadliest cancers worldwide. The majority of patients present with advanced disease and despite decades of work, overall survival rates are still very low. Recent advances in treatment modalities have increased the risk/benefit ratio for these patients and this may translate into increased survival rates. A better understanding of the genetic heterogeneity of lung cancer has led to a new patient classification scheme that may help inform on patient selection for future trials. The topics to be discussed in this symposium include: lung cancer classification, common mutations and insights for patient selection, the use of intraoperative chemotherapy and minimally invasive surgery to treat thoracic cancers, and a discussion on insights from clinical trials using targeted and combination chemotherapy for small cell and non-small cell lung cancers.

Reception to follow.

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Agenda

* Presentation titles and times are subject to change.


March 25, 2014

11:30 AM

Registration

12:00 PM

Welcome and Introduction
Jennifer Henry, PhD, The New York Academy of Sciences
Shashidhar S. Jatiani, PhD, Forest Research Institute

12:10 PM

Evolving Therapies for Early Stage Non-Small Cell Lung Cancer
Jessica S. Donington, MD, NYU Langone Medical Center

12:50 PM

Personalized Therapy for Advanced Non Small Lung Cancer: From the Battle Trial to Master Protocols
Roy S. Herbst, MD, PhD, Yale School of Medicine

1:30 PM

EGFR-mutated Lung Cancer: A Paradigm of Molecular Oncology
Balazs Halmos, MD, Columbia University Medical Center

2:10 PM

Coffee break

2:40 PM

Promising New Agents on the Horizon for NSCLC
Suresh S. Ramalingam, MD, Emory University

3:20 PM

Antibody-mediated Inhibition of Phosphatidylserine: A Novel Strategy for Immune Checkpoint Blockade
Rolf Brekken, PhD, UT Southwestern

4:00 PM

Closing Remarks

Networking Reception

5:00 PM

Close

Speakers

Organizers

Magdalena Alonso-Galicia, PhD

Forest Research Institute

Magdalena Alonso-Galicia, PhD, is a Senior Principal Scientist at the Forest Research Institute, a subsidiary of Forest Laboratories, Inc. in Jersey City, NJ. As a non-clinical pharmacologist, she is responsible for developing and directing pharmacology studies to support approved products and early & late-stage drug candidates in the respiratory and cardiovascular therapeutic areas. She is also the pharmacology reviewer of new licensing opportunities in multiple therapeutic areas such as cardiovascular, respiratory, renal and metabolic disorders. Prior to joining Forest in 2010, she worked in drug discovery at Boehringer Ingelheim and Merck & Co., Inc. in the areas of hypertension, heart failure and chronic kidney diseases. She holds a PhD in Physiology & Biophysics from the University of Mississippi and underwent post-doctoral training at the Medical College of Wisconsin.

Shashidhar S. Jatiani , PhD

Forest Research Institute

Dr. Shashidhar S Jatiani has worked in preclinical anticancer drug discovery and development since 2005. He obtained his Ph.D. in Molecular from Tata Institute for Fundamental Research, Mumbai, India. He currently works as a research scientist in the pharmacology group of Forest Research Institute. Dr. Jatiani has extensive preclinical experience in myeloproliferative neoplasms, leukemias, solid tumors and immuno-oncology.

Huiping Jiang, PhD

Boehringer-Ingelheim Pharmaceuticals

Dr. Huiping Jiang has a bachelor’s degree in biochemistry and a Ph.D. in molecular cell biology. Her postdoctoral research focus was in mammalian genetics and cellular signal transduction. Huiping started her pharmaceutical career at AstraZeneca as a research scientist and then principal scientist at Boehringer Ingelheim Pharmaceuticals Inc. (BIPI) specializing in transgenic pharmacological models. Huiping’s current position is director, regulatory affairs at BIPI. Huiping has been an active steering committee member of BPDG and has contributed to multiple successful NYAS symposiums.

George Zavoico, PhD

HC Wainwright

George B. Zavoico, Ph.D., joined H.C. Wainwright & Co. (HCW), a boutique investment bank and institutional broker-dealer, as Managing Director and Senior Equity Analyst in early 2014. He has over 10 years of experience as a life sciences equity analyst writing research on publicly traded equities. Before joining HCW, Dr. Zavoico was Managing Director and Senior Equity Analyst at MLV & Co., and an Equity Analyst at Westport Capital Markets and Cantor Fitzgerald. Before becoming an equity analyst, Dr. Zavoico established his own consulting company serving the biotech and pharmaceutical industries by providing competitive intelligence and marketing research, due diligence services, and guidance in regulatory affairs. He also wrote extensively on healthcare and the biotech and pharmaceutical industries for periodicals targeting the general public and industry executives. Dr. Zavoico began his career as a Senior Research Scientist at Bristol-Myers Squibb Co., moving on to management positions at Alexion Pharmaceuticals, Inc. and T Cell Sciences, Inc. (now Celldex Therapeutics, Inc.). He has a B.S. in Biology from St. Lawrence University and a Ph.D. in Physiology from the University of Virginia. He held post-doctoral fellowships at the University of Connecticut School of Medicine and at Harvard Medical School/Brigham & Women's Hospital. He has published over 30 papers in peer-reviewed journals and has co-authored four book chapters.

Jennifer Henry, PhD

The New York Academy of Sciences

Speakers

Rolf Brekken, PhD

UT Southwestern

Dr. Brekken grew up in Grapevine, TX, received his BA in Biology from Luther College in Decorah, IA and his PhD (Cell and Molecular Biology) from UT Southwestern Medical Center where he trained under Dr. Philip Thorpe. His graduate studies were focused on developing novel therapies that target the vascular compartment of tumors. He was a postdoctoral fellow in the Department of Vascular Biology at the Hope Heart Institute in Seattle, WA where he studied how the extracellular matrix contributes to vascular function and tumor progression. He joined the Department of Surgery at UT Southwestern as faculty in 2002 and was promoted to Associate Professor with tenure in 2009. His laboratory is located in the Hamon Center for Therapeutic Oncology Research and he is also a member of the Simmons Comprehensive Cancer Center at UT Southwestern. In broad terms Dr. Brekken’s laboratory studies the tumor microenvironment. His group is interested in how therapy affects the tumor microenvironment and how stromal elements influence response to therapy. Current studies in the laboratory focus on: the function of matricellular proteins (SPARC and fibulin-5) in cancer; the biology of anti-VEGF therapy; the contribution of macrophages and other immune cells to the metastatic cascade; and phosphatidylserine-mediated immune suppression in tumors. Dr. Brekken is the Effie Marie Cain Scholar in Angiogenesis Research and receives funding from the ACS, NCI, DOD, CPRIT, Mary Kay Foundation and biopharmaceutical companies. He is an author on over 100 peer-reviewed scientific papers and is a senior editor for Cancer Research.

Jessica S. Donington, MD

NYU Langone Medical Center

Dr. Jessica Donington is a General Thoracic Surgeon at NYU School of Medicine.  She is an associate professor in the Department of Cardiothoracic Surgery, the director of the NYU Thoracic Oncology Translational Laboratory and chief of the Thoracic Surgery Service at Bellevue Hospital.  Her laboratory work focuses on the discovery and validation of diagnostic and prognostic biomarkers for thoracic malignancies and on the role of osteopontin, a ubiquitous protein, in carcinogenesis. Her clinical and interests focus on the diagnosis and treatment of mesothelioma and non-small cell lung cancer. Areas of clinical expertise include the use of multimodality therapy for thoracic malignancies, treatment options for high risk patients with early stage lung cancer and cancer in women. 

Balazs Halmos, MD

Columbia University Medical Center

Balazs Halmos is an Associate Professor of Medicine at Columbia University and Section Chief of Thoracic Oncology at New York Presbyterian Hospital- Columbia. Besides maintaining an active clinical practice focused on the management of patients with malignancies of the thoracic cavity, Dr. Halmos oversees the thoracic clinical trials program at Columbia. He also runs a translational research laboratory investigating novel ways of overcoming resistance to conventional as well as targeted therapeutics. In addition, he is Chair of the Cancer IRB of Columbia University.

Roy S. Herbst, MD, PhD

Yale School of Medicine

Dr. Roy S. Herbst is Ensign Professor of Medicine, Professor of Pharmacology, Chief of Medical Oncology, Director of the Thoracic Oncology Research Program, and Associate Director for Translational Research at Yale Comprehensive Cancer Center and Yale School of Medicine in New Haven, CT. Dr. Herbst has led the Phase I development of several of the new generation of targeted agents for NSCLC, including gefitinib, erlotinib, cetuximab, and bevacizumab. He is co-lead for the BATTLE-1 effort, co-leads the subsequent BATTLE-2 clinical trial program, and serves as a Co-Program Leader of the Developmental Therapeutics Program for the YCC Cancer Center Support Grant (CCSG). He is a member of the National Cancer Policy Forum for which he has organized an IOM meeting focused on policy issues in personalized medicine. His laboratory work is focused on angiogenesis and dual EGFR/VEGFR inhibition in NSCLC. Previously, Dr. Herbst served as the Barnhart Distinguished Professor and Chief of the Section of Thoracic Medical Oncology in the Department of Thoracic/Head and Neck Medical Oncology, at The University of Texas M.D. Anderson Cancer Center in Houston, Texas. He also served as Professor in the Department of Cancer Biology and Co-Director of the Phase I Program. Dr. Herbst is author or co-author of more than 250 publications, including peer-reviewed journal articles, abstracts, and book chapters. He has contributed his work to many prominent journals, such as Journal of Clinical Oncology, Clinical Cancer Research, Lancet, and the New England Journal of Medicine. Dr. Herbst is an active member of ASCO, AACR, IASLC (International Association for the Study of Lung Cancer), RTOG (Radiation Therapy Oncology Group), and SWOG (Southwest Oncology Group Lung Committee). 

Suresh S. Ramalingam, MD

Emory University

Dr. Suresh Ramalingam received his medical degree at Kilpauk Medical College, Madras, India. He completed his residency in Internal Medicine at Wayne State University, Detroit, MI, where he also served as a Chief Medical Resident. He then completed a fellowship in Hematology and Medical Oncology at the University of Pittsburgh Medical Center, Pittsburgh, PA. He is certified by the American Board of Internal Medicine in Internal Medicine and Medical Oncology and is an active member of American Society of Clinical Oncology, the American Association for Cancer Research, and the International Association of Lung Cancer Study. Dr. Ramalingam plays an active role in the ECOG-ACRIN Cancer Research Group as the Chair of the Thoracic Malignancies Committee. He also serves on the editorial board of leading cancer journals such as Journal of Clinical Oncology, Cancer, Clinical Lung Cancer and Cancer, Chemotherapy and Pharmacology. Dr. Ramalingam is the recipient of several awards, including the ‘James Eckman Award for Excellence in Teaching’, Department of Hematology and Medical Oncology, Emory University, and the Distinguished Cancer Scholar Award, Georgia Cancer Coalition. In addition, he is also a recipient of the ‘ASCO Career Development Award’ (2006-09). Dr. Ramalingam serves on several international, national and Institutional Committees.

Sponsors

Academy Friend

Peregrine Pharmaceuticals, Inc.

Grant Support

This program is supported in part by a grant from Genentech Inc.

Promotional Partners

The International Association for the Study of Lung Cancer

LUNGevity

Nature

North Jersey Section American Chemical Society

The Biochemical Pharmacology Discussion Group is proudly supported by



  • Merck
  • WilmerHale

Mission Partner support for the Frontiers of Science program provided by Pfizer

Abstracts

Evolving Therapies for Early Stage Non-Small Cell Lung Cancer
Jessica S. Donington, NYU Langone Medical Center

The standard treatment for stage I non-small cell lung cancer (NSCLC) is lobectomy with systematic mediastinal lymph node evaluation. Unfortunately, up to 25% of patients with stage I NSCLC are not candidates for lobectomy due to severe medical co-morbidity. Additionally it is anticipated that an increasing number of very small cancers detected through CT screening initiatives. Therefore there is a large impetuous to make the treatment less invasive and better tolerated. Minimally invasive approaches (VATS and robotic) lobectomy appear to be better tolerated than open procedures with shorter hospital stay and fewer complications. This benefit appears to be greatest in the high risk population, where a significant decrease in pulmonary complications has been reported. Alternative treatment options to lobectomy for high-risk patients include sublobar resection, stereotactic body radiation therapy (SBRT), and radiofrequency ablation (RFA). Each is associated with decreased procedural morbidity and mortality but increased risk for involved lobe and regional recurrence compared with lobectomy, but direct comparisons between modalities are lacking. Therapeutic options for the treatment of early stage NSCLC are evolving quickly. Improved radiographic staging and the diagnosis of smaller and more indolent tumors push the risk-benefit decision toward parenchymal sparing or non-operative therapies in high-risk patients. Unbiased assessment of treatment options high-requires uniform reporting of treatment populations and outcomes in clinical series, which has been lacking to date.
 

Personalized Therapy for Advanced Non Small Lung Cancer: From the Battle Trial to Master Protocols
Roy S. Herbst, Yale School of Medicine

New strategies incorporating a personalized medicine approach for NSCLC treatment are increasingly explored and were pioneered in the prospective, biomarker-driven clinical program titled Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE-1) Cancer Discov 2011;1:44). Effective therapeutic strategies for mutant KRAS and other biomarkers of resistance in refractory NSCLC remain an unmet medical need. The BATTLE-2 clinical study is using EGFR, PI3K/AKT and MEK inhibitors and is designed to identify biomarkers for optimal patient selection for these therapies, with a long-term goal to significantly improve the survival of NCSLC patients (pts) (ClinicalTrials.gov NCT01248247). In this presentation, the BATTLE biomarker based approaches for lung cancer drug discovery and marker validation will be presented and discussed. Recent efforts at "Master Protocol" designs which will hopefully help with targeted drug approvals will also be presented.
 

EGFR-mutated Lung Cancer: A Paradigm of Molecular Oncology
Balazs Halmos, Columbia University Medical Center

The development of EGFR tyrosine kinase inhibitors for clinical use in non-small cell lung cancer exemplifies the power and promise of modern molecular oncology. This talk will review key paradigms learned as to the molecular testing and classification of non-small cell lung cancers as well as state-of-the-art diagnostic and treatment algorithms. Pivotal primary and acquired resistance mechanisms guiding further clinical development of novel agents will also be highlighted with a specific focus on the recent FDA approval of the irreversible HER kinase inhibitor, afatinib as well as ongoing studies of novel agents targeting bypass resistance mechanisms and the key EGFR T790M resistance mutation.
 

Promising New Agents on the Horizon for NSCLC
Suresh S. Ramalingam, Emory University

Lung cancer has entered a new era of individualized therapies based on targeting specific tumor characteristics, during the past few years. On the forefront of these strategies are targeted therapies for patients with EGFR mutation and ALK translocation. It is estimated that nearly 60% of the patients with lung adenocarcinoma, and 55% of those with squamous cell histology, will have a dominant targetable molecular abnormality. Novel agents are presently under evaluation for specific molecular targets with encouraging initial results in patients with rearrangement of ROS1 and RET, and B-RAF mutations. Despite these exciting developments, a number of patients that do not have a ‘targetable mutation’, or patients with K-Ras mutation for whom no specific therapy exists, require novel approaches. A promising strategy to target multiple molecular pathways involves inhibition of heat shock protein 90(HSP90). This protein serves as a critical chaperone for > 200 oncoproteins, many of which are highly relevant in patients with lung cancer. Inhibiting Hsp90 provides the ability to interrupt multiple oncogenic signaling pathways. Several drugs belonging to the new generation of Hsp90 inhibitors have demonstrated promising results in phase 1 and 2 studies. Ganetespib, a non-geldanamycin inhibitor, has shown single agent activity in NSCLC in specific molecular subsets. In a phase 2 study, the combination of docetaxel and ganetespib demonstrated improved efficacy in a clinically enriched subset of patients with advanced NSCLC. These encouraging results have led to an ongoing phase 3 study (GALAXY-2) in second line therapy for advanced lung adenocarcinoma. Other novel Hsp90 inhibitors such as AUY-922 have also yielded promising results when given in combination with EGFR inhibitors. ALK is a sensitive client protein for Hsp90 and this accounts for single agent responses observed in ALK positive patients treated with a Hsp90 inhibitor. Taken together, the newer generation of Hsp90 inhibitors have a promising role to play in the treatment of lung cancer. Another group of compounds that are presently under evaluation include the PARP inhibitors, that play critical roles in DNA repair. PARP inhibition is highly relevant in the setting of treatment with DNA damaging agents such as platinum compounds and ionizing radiotherapy. Veliparib, a PARP inhibitor, has demonstrated promising early results upon co-administration with carboplatin and paclitaxel. Ongoing studies will seek to confirm these observations in patients with advanced NSCLC.
 

Antibody-mediated Inhibition of Phosphatidylserine: A Novel Strategy for Immune Checkpoint Blockade
Rolf Brekken, UT Southwestern

Phosphatidylserine (PS) is a potent immunosuppressive lipid typically segregated to the inner leaflet of the plasma membrane. PS is externalized on tumor vasculature, tumor-derived exosomes, and tumor cells in the tumor microenvironment and externalization is enhanced by therapy. Externalized PS interacts with immune cells where it actively promotes expansion of myeloid derived suppressor cells (MDSCs) and M2-like tumor associated macrophages (TAMs), which drive immunosuppression and tumor progression. Bavituximab is a PS-targeting antibody that is being evaluated clinically in cancer patients. In preclinical studies, treatment of tumor-bearing mice with 2aG4 or mch1N11 (murine-versions of bavituximab) significantly depleted M2-likeTAMs and MDSCs and increased the presence of M1-like TAMs and mature dendritic cells. In addition, PS blockade shifted the cytokine balance in the tumor microenvironment from immunosuppressive to immunostimulatory. Furthermore, in the immune-competent tumor models combination of standard of care therapy with PS blockade induced potent durable tumor-specific T-cell immunity and significantly improved tumor free long-term survival. These data suggest that externalized PS defines a global immune checkpoint in tumors and support that antibody-mediated PS blockade can reverse PS-mediated immune checkpoint suppression, revitalize innate and the adaptive immunity, and promote therapeutically effective anti-tumor immunity.
 

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