`
`Harvard Medical School
`Curriculum Vitae
`
`
`Date Prepared:
`
`February 1, 2017
`
`Name:
`
`Matthew H. Kulke
`
`Office Address: Dana-Farber Cancer Institute
`
`450 Brookline Ave, D 1220A
`
`Boston, MA 02215 United States
`
`Home Address:
`
`344 Russett Road
`
`Chestnut Hill, MA 02467 United States
`
`Work Phone:
`
`(617) 632-5136
`
`Work Email:
`
`matthew_kulke@dfci.harvard.edu
`
`Work FAX:
`
`(617) 632-5370
`
`Place of Birth:
`
` Palo Alto, CA
`
`Education
`
`
`
`1987
`
`1992
`
`B.A.
`Magna cum laude
`MD
`Alpha Omega Alpha
`
`Molecular Biology
`
`Medicine
`
`2007
`
`M.M.Sc.
`
`Medicine
`
`Postdoctoral Training
`
`
`
`07/01/1992-
`06/30/1993
`07/01/1993-
`06/30/1994
`07/01/1994-
`06/30/1995
`07/01/1995-
`06/30/1997
`
`Intern
`
`Medicine
`
`Junior Assistant
`Resident
`Senior Assistant
`Resident
`Clinical Fellow
`
`Internal Medicine
`
`Internal Medicine
`
`Oncology
`
`Faculty Academic Appointments
`
`
`Instructor
`07/97-06/01
`07/01-06/08 Assistant Professor
`07/08-07/16 Associate Professor
`07/16-
`Professor
`
`Medicine
`Medicine
`Medicine
`Medicine
`
`1
`
`Princeton University,
`Princeton, NJ
`University of California,
`San Francisco School of
`Medicine
`San Francisco, CA
`Harvard Medical School
`Boston, MA
`
`Brigham and Women’s
`Hospital, Boston, MA
`Brigham and Women’s
`Hospital,
`Brigham and Women’s
`Hospital,
`Dana-Farber Cancer
`Institute (DFCI), Boston,
`MA
`
`Harvard Medical School
`Harvard Medical School
`Harvard Medical School
`Harvard Medical School
`
`
`
`NOVARTIS EXHIBIT 2042
`Par v. Novartis, IPR 2016-01479
`Page 1 of 35
`
`

`

`
`
`Appointments at Hospitals/Affiliated Institutions
`
`
`07/97-
`
`Associate Physician
`
`Medicine
`
`07/97-
`
`Attending Physician
`
`Medical Oncology
`
`07/12-
`
`Senior Physician
`
`Medical Oncology
`
`Brigham and Women’s
`Hospital
`Dana-Farber Cancer
`Institute
`Dana-Farber Cancer
`Institute
`
`
`Major Administrative Leadership Positions
`
`2010-
`
`Director, Program in Neuroendocrine and Carcinoid Tumors Dana-Farber Cancer
`Institute/Brigham and
`Women’s Cancer Center,
`Boston, MA
`
`Committee Service
`
`Local
`
`
`
`1998-2008
`
`Chairperson, Cardiopulmonary
`Resuscitation (CPR) Committee
`1998-2005 Member, Fellowship Selection Committee
`2007-2008 Member, Scientific Progress Review
`Committee
`Chair, Clinical Information and
`Biospecimen User Committee,
`Gastrointestinal Cancer Center
`Co-Chair, Clinical Trial Advisory Board
`
`2010-
`
`
`2017
`
`Dana-Farber Cancer Institute
`
`Dana-Farber Cancer Institute
`Dana-Farber Cancer Institute
`
`Dana-Farber Cancer Institute
`
`Dana-Farber Cancer Institute
`
`Bethesda, MD
`
`Fort Washington, PA
`
`
`
`Bethesda, MD
`
`
`
`Cancer and Leukemia Group B
`Gastrointestinal Cancer Core
`Member, 2001-2010
`Committee, 2010-
`National Comprehensive Cancer Network
`Neuroendocrine Tumor Guidelines Panel
`Member, 2005-2010
`Chair, 2010-
`National Cancer Institute Neuroendocrine
`Tumor Task Force
`Member, 2009-2010 and 2014-
`Chair, 2010-2014
`
`
`National
`
`
`
`2001-
`
`2005-
`
`
`
`2009-
`
`International
`
`
`
`2008-2010 Member, Data Safety Monitoring
`Committee, First-Line Advanced Gastric
`Cancer Study (FLAGS)
`
`Taiho Pharmaceuticals, Tokyo,
`Japan
`
`2
`
`
`
`NOVARTIS EXHIBIT 2042
`Par v. Novartis, IPR 2016-01479
`Page 2 of 35
`
`

`

`
`
`2011-2016
`
`2010-2013 Member, Data Safety Monitoring
`Committee, RAD001 in Advanced
`Neuroendocrine Tumors (RADIANT) 2 and
`RADIANT 3 Studies
`Chair, Steering Committee, Efficacy of
`Everolimus Alone or in Combination with
`Pasireotide Long-acting Release (LAR) in
`Advanced Pancreatic Neuroendocrine Tumor
`(PNET) (COOPERATE)-2 Study
`2012-2016 Member, Steering Committee, RADIANT-4
`Study
`Chair, Steering Committee, Telotristate
`Etiprate for Somatostatin Analogue Not
`Adequately Controlled Carcinoid Syndrome
`(TELESTAR) Study
`
`2013-
`
`Novartis Pharmaceuticals, Basel,
`Switzerland
`
`Novartis Pharmaceuticals, Basel,
`Switzerland
`
`Novartis Pharmaceuticals, Basel,
`Switzerland
`Lexicon Pharmaceuticals, The
`Woodlands, TX
`
`
`
`Professional Societies
`
`Member
`Member
`Cancer Education Committee
`Program Committee
`
`Massachusetts Medical Society
`American Society of Clinical Oncology
`2011-2014
`2015-2017
`North American Neuroendocrine Tumor
`Society
`Co-Chair, Scientific Research Committee
`2006-2012
`Vice-Chair
`2012-2014
`Chair
`2014-2016
`Board of Directors
`2014-
`European Neuroendocrine Tumor Society Member, External Advisory Board
`American Association for Cancer Research Member
`
`
`
`
`
`1992-
`1997-
`
`
`
`
`
`
`2006-
`
`
`
`
`2008-
`2009-
`
`
`
`Editorial Activities
`
`Ad hoc Reviewer
`Journal of Clinical Oncology
`Cancer
`Clinical Cancer Research
`Endocrine Related Cancer
`New England Journal of Medicine
`
`
`
`
`
`Other Editorial Roles
`
`Editor
`
`Editorial Board
`
`UpToDate in Medicine (Neuroendocrine
`Tumor Section)
`Journal of Clinical Oncology
`
`
`
`2000-
`
`2001-2003
`
`
`
`3
`
`
`
`NOVARTIS EXHIBIT 2042
`Par v. Novartis, IPR 2016-01479
`Page 3 of 35
`
`

`

`
`
`Honors and Prizes
`
`1987
`
`Regents Scholarship
`
`1989-1992 Medical Student Research Training
`Fellowship
`
`1991
`
`1992
`
`Thesis Honors Award
`
`1998-1999 Young Investigator Award
`
`University of California,
`San Francisco School of
`Medicine, San Francisco,
`CA
`Howard Hughes Medical Institute,
`University of California, San
`Francisco School of Medicine, San
`Francisco, CA
`Alpha Omega Alpha Medical Honor Society University of California, San
`Francisco School of Medicine
`University of California, San
`Francisco School of Medicine
`American Society of Clinical
`Oncology
`Dana-Farber Cancer Institute
`Dana-Farber Cancer Institute
`
`1999-2001 Discovery Fellowship
`2003
`George Canellos Award for Contributions to
`Clinical Research
`Kenneth E Schwarz Center Compassionate
`Care Giver Award
`Ruth Brufsky Award for Excellence in
`Clinical Research on Pancreatic Cancer
`Research
`Lee Nadler Extra Mile Award
`Kenneth E Schwarz Center Compassionate
`Care Giver Award
`
`2008
`
`2009
`
`2010
`2011
`
`Dana-Farber Cancer Institute
`
`University of Pittsburgh School of
`Medicine
`
`Dana-Farber Cancer Institute
`Dana-Farber Cancer Institute
`
`Report of Funded and Unfunded Projects
`
`Principal Investigator, Rhone-Poulenc Rorer., DF/HCC Protocol # 97-121,
`Phase II Study of Docetaxel in Patients with Locally Advanced or Unresectable
`Carcinoid Tumors
`The objective of this study was to assess the efficacy of docetaxel in patients
`with locally advanced or unresectable carcinoid tumors.
`Principal Investigator, Eli-Lilly., DF/HCC Protocol # 99-044, Phase II Study of
`Gemcitabine in Patients with Advanced Neuroendocrine Tumors
`The objective of this study was to assess the efficacy of gemcitabine in patients
`with advanced neuroendocrine tumors.
`Principal Investigator, Glaxowelcome., DF/HCC Protocol # 00-012, Phase II
`Study of Vinorelbine in Patients with Unresectable or Metastatic Esophageal or
`Gastric Adenocarcinoma
`The objective of this study was to assess the efficacy of vinorelbine in patients
`with unresectable or metastatic esophageal or gastric adenocarcinoma.
`Principal Investigator, Pharmacia & Upjohn., DF/HCC Protocol # 01-100, Phase
`II Study of Irinotecan and Cisplatin in Patients with Advanced Neuroendocrine
`Tumors
`
`Past
`1997-2000
`
`1999-2001
`
`2000-2002
`
`2001-2003
`
`
`
`4
`
`
`
`NOVARTIS EXHIBIT 2042
`Par v. Novartis, IPR 2016-01479
`Page 4 of 35
`
`

`

`The objective of this study was to assess the efficacy of irinotecan and cisplatinl
`in patients with advanced neuroendocrine tumors
`Principal Investigator, Entremed, DF/HCC Protocol # 01-114, Phase II Study of
`the Safety and Efficacy of Recombinant Human Endostatin in Patients with
`Advanced Neuroendocrine Tumors
`The objective of this study was to assess the efficacy of recombinant human
`endostatin in patients with advanced neuroendocrine tumors.
`Principal Investigator, CALGB 89904, A Randomized Phase II trial of
`Gemcitabine/Cisplatin, Gemcitabine/Irinotecan, Gemcitabine/Docetaxel, or
`Fixed Dose Rate Infusion Gemcitabine in the Treatment of Patients with
`Metastatic Pancreatic Cancer
`The objective of this study was to compare the efficacy of gemcitabine/cisplatin,
`gemcitabine/irinotecan, gemcitabine/docetaxel, or fixed dose rate infusion
`gemcitabine in patients with metastatic pancreatic cancer.
`Principal Investigator, Celgene., DF/HCC Protocol # 02-011, A Phase II Study
`of Temozolomide and Thalidomide in Patients with Metastatic Neuroendocrine
`Tumors
`The objective of this study was to assess the efficacy of temozolomide and
`thalidomide in patients with metastatic neuroendocrine tumors.
`Principal Investigator, Sugen Inc., DF/HCC Protocol # 02-317, A Phase II Study
`of the Efficacy and Safety of SU011248 in Patients with Advanced Unresectable
`Neuroendocrine Tumor (Multicenter Study)
`The objective of this multi-institutionalstudy was to assess the efficacy of
`SU011248 (sunitinib) in patients with advanced unresectable neuroendocrine
`tumors.
`Principal Investigator, Roche Inc., DF/HCC Protocol # 03-070, A Phase II Study
`of OSI-774 (Tarceva) in Combination with Capecitabine in Patients with
`Metastatic Pancreatic Cancer
`The objective of this study was to assess the efficacy of OSI-774 (Tarceva) in
`combination with capecitabine in patients with metastatic pancreatic cancer.
`Principal Investigator, Taiho Inc., DF/HCC Protocol 03-209, Phase I Study of S-
`1 in Patients with Previously Treated Upper GI Malignancies
`The objective of this study was to assess the safety of the oral fluoropyrimidine
`S-1 in patients with previously treated upper GI malignancies.
`Principal Investigator, National Institute of Health (NIH)/National Cancer
`Institute (NCI), K23 CA 093401, Molecular Prognostic Factors in Esophageal
`Cancer
`The objective of this career-development award was to assess the prognostic
`significance of germline polyphorphisms and tissue-based markers in
`esophogeal cancer.
`Principal Investigator, Genentech., DF/HCC Protocol # 04-272, Phase II Study
`of Temozolomide and Bevacizumab in Patients with Advanced Neuroendocrine
`Tumors
`The objective of this study was to assess the efficacy of temozolomide and
`bevacizumab in patients with advanced neuroendocrine tumors.
`Principal Investigator, Astra-Zeneca, DF/HCC Protocol # 04-173, A Phase II
`Study of Iressa in Combination with Docetaxel in Patients with Metastatic
`Pancreatic Cancer
`
`
`
`
`
`2001-2003
`
`2001-2004
`
`2002-2004
`
`2003-2004
`
`2003-2004
`
`
`
`2003-2004
`
`2003-2008
`
`2004- 2005
`
`2004-2006
`
`5
`
`
`
`NOVARTIS EXHIBIT 2042
`Par v. Novartis, IPR 2016-01479
`Page 5 of 35
`
`

`

`
`
`2005-2007
`
`2006-2010
`
`2007-2008
`
`2007-2009
`
`
`2007-2009
`
`2007-2011
`
`2008-2010
`
`2008-2013
`
`The objective of this study was to assess the efficacy of iressa in combination
`with docetaxel in patients with metastatic pancreatic cancer.
`Principal Investigator, Eli Lilly, DF/HCC Protocol # 05-309, A Phase II Study of
`Pemetrexed in Patients with Advanced Neuroendocrine Tumors
`The objective of this study was to assess the efficacy of pemetrexed in patients
`with advanced neuroendocrine tumors.
`Principal Investigator, EntreMed, Inc, DF/HCC Protocol # 05-389, A Phase I-II
`Safety and Efficacy Study of Panzem Nanocrystal Colloidal Dispersion
`Administered Orally in Combination with RhuMab VEGF (Bevacizumab) in
`Patients with Locally Advanced or Metastatic Carcinoid Tumors
`The objective of this study was to assess the efficacy of the novel angiogenesis
`inhibitor panzem in combination with bevacizumab in patients with locally
`advanced or metastatic carcinoid tumors.
`Principal Investigator, Developmental Project, NIH/NCI P50 A127003,
`DF/HCC Specialized Program in Research Excellence (SPORE) in
`Gastrointestinal Cancer: 06 Methylguanine Methyltransferase (MGMT) and
`Sensitivity of Pancreatic Neuroendocrine Tumors to Temozolomide Therapy
`The objective of this study was to assess the association of deficiency of the
`DNA repair enzyme MGMT and sensitivity of pancreatic neuroendocrine tumors
`to temozolomide therapy
`Principal Investigator, Novartis, DF/HCC Protocol 07-325, Phase I/II Study of
`RAD001 in Combination with Temozolomide in Patients with Advanced
`Pancreatic Neuroendocrine Tumors
`The objective of this study was to assess the efficacy of everolimus and
`temolozomide in patients with advanced pancreatic neuroendocrine tumors.
`Site Principal Investigator, NIH/NCI, N01 CM62202, A Phase II Study of
`GW786034 (Pazopanib) in Advanced Low-grade or Intermediate-grade
`Neuroendocrine Carcinoma
`The objective of this study was to assess the efficacy of pazopanib in patients
`with advanced low-grade or intermediate-grade neuroendocrine carcinoma.
`Site Principal Investigator, Novartis, DF/HCC Protocol # 06-199, An Open-
`Label, Stratified, Single-arm Phase II Study of RAD001 in Patients with
`Advanced Pancreatic Neuroendocrine Tumor (NET) after Failure of Cytotoxic
`Chemotherapy
`The objective of this study was to assess the efficacy of everolimus in patients
`with advanced pancreatic neuroendocrine tumor after failure of cytotoxic
`therapy.
`Principal Investigator, Novartis, DF/HCC Protocol # 08-087 Phase I Study of
`Pasireotide (SOM230) in Combination with RAD001 in Patients with Advanced
`Neuroendocrine Tumors
`The objective of this study was to assess the safety of pasireotide, administered
`with everolimus, in patients with advanced neuroendocrine tumors.
`Site Principal Investigator, Novartis, DF/HCC Protocol 08-221, A multicenter,
`randomized, blinded efficacy and safety study of pasireotide LAR vs octreotide
`LAR in patients with metastatic carcinoid tumors whose disease-related
`symptoms are inadequately controlled by somatostatin analogues
`The objective of this study was to compare the efficacy of pasireotide LAR vs
`octreotide LAR in patients with carcinoid syndrome refractory to standard
`
`6
`
`
`
`NOVARTIS EXHIBIT 2042
`Par v. Novartis, IPR 2016-01479
`Page 6 of 35
`
`

`

`
`
`2008-2013
`
`2009-2011
`
`2009-2011
`
`2009-2014
`
`2009-2014
`
`2010-2011
`
`2010- 2016
`
`2011-2013
`
`2011- 2016
`
`somatostatin analogues.
`CALGB Principal Investigator, CTSU/SWOG, DF/HCC Protocol 08-231, Phase
`III Prospective Randomized Comparison of Depot Octreotide plus Interferon
`Alpha Versus Depot Octreotide Plus Bevacizumab in Advanced, Poor Prognosis
`Carcinoid Patients (NSC#704865)
`The objective of this study was to compare the efficacy of depot octreotide plus
`interferon alpha versus depot octreotide plus bevacizumab in patients with
`advanced carcinoid tumor.
`Principal Investigator, Novartis, Bayer/Onyx, DF/HCC Protocol # 09-094, Phase
`I Study of Sorafenib in Combination with RAD001 in Patients with Advanced
`Neuroendocrine Tumors
`The objective of this study was to assess the safety of sorafenib, administered
`with everolimus, in patients with advanced, neuroendocrine tumors.
`Principal Investigator, Endo Pharmaceuticals, DF/HCC Protocol # 09-218,
`Open-Label Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of
`Two Doses of an Octreotide Implant in Patients with Carcinoid Syndrome.
`The objective of this study was to assess the efficacy of two doses of an
`octreotide implant in patients with carcinoid syndrome.
`Principal Investigator, Lexicon Pharmaceuticals, DF/HCC Protocol # 09-038, A
`Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled,
`Ascending, Multi-Dose Study to Determine the Safety and Tolerability of Orally
`Administered LX1606 in Subjects with Symptomatic Carcinoid Syndrome
`Refractory to Stable-Dose Octreotide Long-Acting Release Depot Therapy
`The objective of this study was to assess the safety and efficacy of orally
`administered LX1606 in patients with carcinoid syndrome refractory to
`octreotide.
`Principal Investigator, Amgen, DF/HCC Protocol 09-240, A Multi-Institutional,
`Phase II Open-Label Study of AMG 479 in Advanced Carcinoid and Pancreatic
`Neuroendocrine Tumors
`The objective of this multi-institutional study was to assess the efficacy of AMG
`479 in patients with advanced carcinoid and pancreatic neuroendocrine tumors.
`Principal Investigator, Developmental Project, NIH/NCI, P50 CA127003.,
`DF/HCC SPORE in Gastrointestinal Cancer: Molecular Predictors of
`Neuroendocrine Tumor Risk and Outcome
`The objective of this study was to assess molecular predictors of neuroendocrine
`tumor risk and outcome.
`Principal Investigator, CALGB, Randomized Phase II Study of Everolimus
`Alone versus Everolimus Plus Bevacizumab in Patients with Locally Advanced
`or Metastatic (10-399),
`The objective of this multi-institutional study is to assess progression-free
`survival rate of patients with locally advanced or metastatic pancreatic
`neuroendocrine tumors treated with everolimus alone or everolimus plus
`bevacizumab.
`Principal Investigator, Novartis, CRAD001KUS172T, Molecular Predictors of
`Neuroendocrine Tumor Risk and Outcomes
`The objective of this study was to assess molecular predictors of neuroendocrine
`tumor risk and outcomes.
`Principal Investigator, Novartis, A Randomized Open-Label Phase II Multi-
`
`7
`
`
`
`NOVARTIS EXHIBIT 2042
`Par v. Novartis, IPR 2016-01479
`Page 7 of 35
`
`

`

`
`
`2011-2015
`(NCE July
`2016)
`
`2012-2015
`
`
`2012-2016
`
`2012-2014
`
`
`
`2013-2015
`
`
`
`2013-2016
`
`2014-2015
`
`2015-2016
`
`Institutional Study Evaluating the Efficacy of Oral Everolimus Alone or in
`Combination with Pasireotide LAR in Advanced, Progressive Pancreatic
`Neuroendocrine Tumors (COOPERATE-2) (DF/HCC #11-375). The objective
`of this study is to evaluate the efficacy of the novel somatostatin analog
`administered in combination with everolimus to the efficacy of everolimus alone
`in patients with advanced pancreatic NET.
`Principal Investigator, NIH, Molecular and Genetic Predictors of
`Neuroendocrine Tumors Risk and Survival; 1 R01 CA151532-01A1. We are
`performing a two-stage candidate SNP approach to identify and then confirm
`genetic predictors of risk or survival in candidate molecular pathways implicated
`in neuroendocrine tumors. We are additionally identifying and validating
`immunohistochemical predictors of survival for in these same pathways.
`Principal Investigator, Ipsen Pharmaceuticals, Biomarkers of Clinical Outcome
`in Neuroendocrine Tumors
`The objective of this project was to characterize the expression of somatostatin
`receptors in neuroendocrine tumors, assess the effect of genetic variation in
`these receptors, and explore the use of miRNAs as biomarkers of clinical
`outcome in neuroendocrine tumors.
`Site Principal Investigator, Novartis, Phase III Study of Everolimus Plus Best
`Supportive Care Versus Placebo Plus Best Supportive Care in the Treatment of
`Patients with Advanced NET of GI or Lung Origin (RADIANT-4) (DF/HCC
`#12-157). This is a registration study to evaluate the efficacy of everolimus
`compared to placebo in patients with advanced carcinoid tumors.
`Principal Investigator, Novartis, Evaluation of Octreotide LAR Dose
`Optimization and Clinical Outcomes in Patients with Neuroendocrine Tumors: a
`Retrospective Chart Review Study. The objective of this study was to assess
`octreotide LAR dose optimization and clinical outcomes in patients with
`neuroendocrine tumors
`Co-Investigator, Caring for Carcinoid Foundation, Identifying the Epigenetic
`State in Carcinoid and Pancreatic Neuroendocrine Tumors
`The objective of this study was to evaluate epigenetic changes in neuroendocrine
`tumors with the goal of identifying epigenetic aberrations that may lead to the
`identification of novel treatment targets.
`Principal Investigator, Lexicon, Randomized Placebo-Controlled, Parallel-
`Group Multicenter, Double-Blind Study to Evaluate the Efficacy and Safety of
`Telotristat Etiprate (LX1606) in Patients with Carcinoid Syndrome Not
`Adequately Controlled by Somatostatin Analog Therapy (DF/HCC #13-057).
`This is a registration study to evaluate the efficacy of the serotonin synthesis
`inhibitor telotristat in patients with carcinoid syndrome
`Principal Investigator, Ipsen Pharmaceuticals, Generation of Real-World
`Evidence for Neuroendocrine Tumors from an Institutional Database. The
`objective of this project was to evaluate treatment patterns, clinical outcomes,
`and associated costs in a large cohort of patients with neuroendocrine tumors
`using data from a prospectively collected institutional database.
`Principal Investigator, Caring for Carcinoid Foundation, Investigation of the
`immune environment of neuroendocrine tumors, The objectives of this project
`are to evaluate immune markers and immune response in neuroendocrine
`tumors, with the goal of obtaining preliminary data to guide potential immune
`
`8
`
`
`
`NOVARTIS EXHIBIT 2042
`Par v. Novartis, IPR 2016-01479
`Page 8 of 35
`
`

`

`
`
`therapies for this disease.
`
`
`Current
`2007-2017 Co-Investigator
`
`NIH/NCI, P50 CA127003
`
`
`
`
`
`2013-
`
`completion
`of accrual
`
`DF/HCC SPORE in Gastrointestinal Cancer: Core 2 – Tissue and Pathology Core
`The DF/HCC SPORE Tissue and Pathology Core provides clinically annotated tissue resources for
`translational research projects associated with the SPORE.
`
`Advanced Accelerator Applications (AAA)
`
`Site Principal
`Investigator
`A Multi-Center, Stratified, Open Randomized Comparator-Controlled, Parallel-Group
`Phase III Study Comparing Treatment with 177Lu-DOTA-Tyr3 Octreotate to Octreotide
`LAR in Patients with Inoperable, Progressive, Somatostatin-Receptor Positive, Midgut
`Carcinoid Tumors (DF/HCC #13-282)
`
`$272,124
`
`
`
`This is a registration study to evaluate the efficacy of radiopeptide therapy in patients with
`advanced carcinoid tumors.
`
`2013-2018 Co-Investigator
`
`
`NIH/NCI, 1R01CA166582
`
`
`
`Positron Emission Tomography (PET) imaging of carcinoid tumors to guide individualized
`chemotherapy
`This project focuses on novel imaging methods for the characterization of carcinoid tumors
`
`2016-2017
`
`Principal Investigator
`
`Caring for Carcinoid Foundation
`
`$100,000
`
`
`
`
`
`2016-2018
`
`
`
`2016-2019
`
`Investigation of the immune environment of neuroendocrine tumors
`The objectives of this project are to evaluate immune markers and immune response in
`neuroendocrine tumors, with the goal of obtaining preliminary data to guide potential immune
`therapies for this disease.
`Principal Investigator
`
`$371,964
`
`Ipsen
`
`Novel Biomarkers in Neuroendocrine Tumors
`Goals of this proposal are: To assess expression patterns of D2R and GIP-1 on large cohort of
`neuroendocrine tumors and to assess associations between expression of D2R and GIP-1 and
`expression of somatostatin receptors, as well as clinical outcomes. A second goal is to assess
`microRNA expression patterns in clinical subgroups of patients with small bowel carcinoid tumors,
`and to explore microRNA expression patterns in a new cohort pancreatic neuroendocrine tumors.
`Principal Investigator
`Novartis
`$65,000
`
`Multi-Center Chart Review Study in the US to Examine Treatment Patterns and Associated
`Outcomes among Patients with Advanced Neuroendocrine Tumors of Gastrointestinal (GI)
`and Lung Origin
`This multi-center retrospective chart review study will characterize the real-world systemic
`treatment patterns of GI NET patients at tertiary cancer centers, and define unmet needs in the
`current standard of care.
`2016-2017 Principal Investigator
`
`$66,136
`
`Ipsen
`
`Treatment Patterns and Resource Utilization in Patients with Advanced Neuroendocrine
`Tumors
`Goals of this proposal are to evaluate treatment patterns and associated costs in patients with
`advanced neuroendocrine tumors, using data from an institutional database in conjunction with
`date from electronic health medical records
`Principal Investigator
`Dana-Farber Cancer Institute
`
`
`
`9
`
`
`
`
`
`
`
`
`
`
`
`2016-
`
`NOVARTIS EXHIBIT 2042
`Par v. Novartis, IPR 2016-01479
`Page 9 of 35
`
`

`

`
`
`completion Lanreotide Autogel in Lung Neuroendocrine Tumors (DF/HCC Protocol # 16-032)
`of accrual
`The objective is to compare the antitumour efficacy of LAN plus BSC every 28 days monotherapy
`versus placebo plus BSC, in terms of progression free survival (PFS), measured by central review
`using Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 criteria, every 12 weeks, in
`subjects with unresectable and/or metastatic well differentiated, typical or atypical lung
`neuroendocrine tumours.
`
`Dana-Farber Cancer Institute
`Principal Investigator
`2016-
`completion PEN-221 in SSTR2 Expressing Advanced Cancers (DF/HCC Protocol # 16-450)
`of accrual
`The objective is to investigate the safety and tolerability, determine the MTD, and preliminary
`antitumor activity of PEN-221 when administered IV on an every 3 week schedule in patients with
`SSTR2-expressing advanced cancers, including GEP or lung or thymus or other NETs or SCLC or
`LCNEC of the lung.
`Principal Investigator
`
`Neuroendocrine Tumor Research Foundation $100,000
`
`2017-2018
`
`
`
`
`2017-2019
`
`
`
`Profiling of Secreted Immune Mediators in Neuroendocrine Tumors
`The objectives of this proposal are to explore patterns of secreted immune mediators in
`neuroendocrine tumors, and to explore the activity of immune checkpoint inhibitors in an ex-vivo
`neuroendocrine tumor model.
`Principal Investigator
`Ipsen
`
`$233,016
`
`Novel Ex-vivo Organotypic Neuroendocrine Tumor Tissue Slice Cultures
`The objective of this project is to develop an ex-vivo model of neuroendocrine tumors and to
`explore the effects of novel therapeutics in this model.
`
`2003-
`completion
`of accrual
`
`2013-
`completion
`of accrual
`
`
`Current Unfunded
`
`DFCI
`2003-
`Principal Investigator
`completion
`Collection of biologic samples and clinical data in Patients with Neuroendocrine
`of accrual
`Tumors (DF/HCC Protocol # 02-314)
`The objective of this study is to develop a clinical information and biospecimen bank for
`patients with neuroendocrine tumors evaluated at DFCI.
`
`Principal Investigator
`DFCI
`Collection of Biologic Samples and Clinical Data in Patients with Gastrointestinal
`Malignancies (DF/HCC Protocol # 03-189)
`The objective is to develop a clinical information and biospecimen bank for patients with
`gastrointestinal malignancies seen at DFCI.
`
`Principal Investigator
`DFCI
`Molecular Analysis of Neuroendocrine Tumor Risk and Outcome (DF/HCC Protocol
`# 13-118)
`The purpose of this study is to collect and utilize the biospecimens and clinical outcome
`data collected under DF/HCC Protocol 02-314 (Collection of Clinical Information and
`Biological Samples from Patients with Neuroendocrine Tumors)
`
`Principal Investigator
`DFCI
`Improving Staging of Gastroenteropancreatic Neuroendocrine Tumors (DF/HCC
`Protocol # 14-284)
`The object is to retrospectively assess the accuracy and predictive value of staging of
`gastroenteropancreatic neuroendocrine tumors seen at DFCI.
`
`2014-
`completion
`of accrual
`
`10
`
`
`
`
`
`NOVARTIS EXHIBIT 2042
`Par v. Novartis, IPR 2016-01479
`Page 10 of 35
`
`

`

`
`
`
`
`
`
`Report of Local Teaching and Training
`Formal Teaching of Residents, Clinical Fellows, and Research Fellows (post-docs)
`2010-
`Gastrointestinal Cancer Clinical Case
`Two 1-hour sessions per year
`Conference, a case-based conference for
`Clinical Oncology Fellows to present and
`discuss GI cancer cases with Attending
`Oncologists
`
`Laboratory and Other Research Supervisory and Training Responsibilities
`2003-
`Supervision and training of research
`2 hours per week
`assistants for the gastrointestinal cancer
`clinical information and biospecimen
`database
`Supervision and training of two post-
`doctoral fellows
`
`Clinical Supervisory and Training Responsibilities
`1997 –
`Supervision and training Clinical Oncology
`Fellows in the outpatient clinic. Clinical
`Fellows co-manage gastrointestinal cancer
`patients with me at DFCI.
`Inpatient attending on the Oncology service
`at Brigham and Women’s Hospital. While
`on service, I directly supervise and train
`BWH Housestaff, as well as an occasional
`DFCI Oncology Fellow.
`
`Formally Supervised Trainees and Faculty
`1997-1999
`Kosha Thakore, MD/ Hospitalist, Newton Wellesley Hospital
`Research supervisor - Published 2 manuscripts, including evaluations of
`microsatellite instability and loss of the tumor suppressor gene phosphatase
`and tensin (PTEN) in Esophageal Cancer.
`
`2011-
`
`Regular interaction at least 3 days/week
`
`2 hours per week
`
`1997 –
`
`2 weeks per year
`
`2004-2010
`
`2007-
`
`Christine Frauenhoffer, MBA/ Senior Consultant, ECG Management
`Consultants
`Research supervisor - Published 3 manuscripts, including evaluation of DNA
`repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT) in
`neuroendocrine tumors.
`
`Jennifer Chan, MD/ Assistant Professor of Medicine HMS, Clinical Director,
`Neuroendocrine Tumor Program, DFCI
`Research mentor - Published 19 manuscripts, including both review articles
`and novel clinical investigations in neuroendocrine tumors. Had a podium
`presentation at 2017 ASCO Gastrointestinal Cancer Symposium and selected
`as Principal Investigator for a large, randomized registration trial of
`cabozantinib in neuroendocrine tumors, sponsored by ALLIANCE.
`
`2010-2012
`
`Daniel Halperin, MD/ Assistant Professor of Medicine, Gastrointestinal
`Oncology, MD Anderson Cancer Center
`Research mentor - Published 2 review articles on neuroendocrine tumors
`
`11
`
`
`
`NOVARTIS EXHIBIT 2042
`Par v. Novartis, IPR 2016-01479
`Page 11 of 35
`
`

`

`
`
`2010-
`
`during residency at BWH.
`
`Ziron Qian MD, PhD/ Instructor in Medicine, Dana-Farber Cancer Institute
`Research supervisor - Published 4 manuscripts, including first-author
`manuscript in Journal of Clinical Oncology evaluating mTOR pathway in
`Neuroendocrine Tumors. Had 3 oral abstract presentations, and has won
`young investigator awards from the North American Neuroendocrine Tumor
`Society and European Neuroendocrine Tumor Society for work in molecular
`pathogenesis of neuroendocrine tumors.
`
`2010-2016 Monica Ter-Minassian, MD, ScD/ Staff Scientist, Kaiser Permanente,
`Rockville Maryland
`
`2010-
`
`2016-
`
`Research supervisor - Published 6 manuscripts on genetic epidemiology of
`neuroendocrine tumors, received a training grant from the Raymond and
`Beverly Sackler Foundation, and had an oral abstract presentation at the
`North American Neuroendocrine Tumor Society annual meeting.
`Lauren Brais, MPH. Project Manager, Gastrointestinal Oncology
`Biospecimen Database
`
`Research supervisor - Published 8 manuscripts and currently leads group of
`research data specialists for Gastrointestinal Cancer Biospecimen Database
`at Dana-Farber Cancer Institute.
`AnnaCarolina DaSilva, MD/Research Fellow, Dana-Farber Cancer Institute
`Research supervisor- abstract on immune environment of neuroendocrine
`tumors was selected as a podium presentation at the 2016 North American
`Neuroendocrine Tumor Society. Won travel grant to present results at the
`European Neuroendocrine Tumor Society in 2017.
`
`
`Formal Teaching of Peers
`* presentations below were sponsored by outside entities.
`
`2002-2004
`
`2002-2016
`
`2013, 2015,
`2016
`2016
`
`Gastrointestinal Malignancies
`Harvard Medical School Postgraduate Course: Intensive
`Review of Internal Medicine
`Neuroendocrine Tumors
`Harvard Medical School Postgraduate Course: Cancer
`Medicine and Hematology
`Neuroendocrine Tumors
`Topics in GI Malignancies/Harvard Medical School
`Course Director, Expertise Exchange Educational
`Program in NET: New Advances in the Biology and
`Treatment of Neuroendocrine Tumor
`*Sponsored by Ipsen
`
`Annual Presentation
`Boston, MA
`
`Annual Presentation
`Boston, MA
`
`Semi- Annual Presentation
`Boston, MA
`Single Presentation,
`Boston, MA
`
`
`Local Invited Presentations
`* presentations below were sponsored by outside entities
`
`2010
`
`Targeted Therapies for Gastrointestinal Neuroendocrine tumors: current status
`and future directions/ MGH Oncology Grand Rounds/ Invited Lecture,
`
`12
`
`
`
`NOVARTIS EXHIBIT 2042
`Par v. Novartis, IPR 2016-01479
`Page 12 of 35
`
`

`

`Massachusetts General Hospital, Boston, MA
`Management of Neuroendocrine Tumors/Invited Lecture/ Beth Israel
`Deaconess Medical Center/ Longwood Area Endocrine Fellow’s Didactic
`Series, Boston, MA
`Beth Israel Deaconess Medical Center, Boston, MA
`Current management of neuroendocrine tumors/Nuclear Medicine and
`Molecular Imaging Seminar Series /Invited Lecture
`Massachusetts General Hospital, Boston, MA
`GI/Neuroendocrine/Carcinoid Tumors/ Harvard Medical School
`Endocrinology Board Review Course/ Invited Lecture, Boston, MA
`Targeted Therapies in Neuroendocrine Tumors: Therapeutic and Biological
`Implications/ 8th Annual DF/HCC Lung Cancer Symposium/ Invited Lecture,
`Dana-Farber Cancer Institute, Boston, MA
`Neuroendocrine Tumors Imaging Program Invited Lecture, Dana-Farber
`Cancer Institute, Boston, MA
`Neuroendocrine Tumors/Cancer Medicine and Hematology Course/Invited
`Lect