A JOHNS HOPKINS SINGAPORE ANNUAL RESEARCH REPORT 2015 15 years of excellence in patient care, research, and education The Promise of Medicine: The research team at Johns Hopkins Singapore provides unparalleled excellence in their search for ground breaking treatment options.
The office of research at Johns Hopkins Singapore (JHS) is fully integrated with the Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center (SKCCC) and is staffed by six (6) investigators and six (6) coordinators. The program continues to become more robust as additional studies are added annually. In 2015, the office of research coordinated and managed a total of thirty-two (32) studies that fall into three (3) categories: Seventeen (17) studies were opened for recruitment. The studies examine treatments for different types and stages of lung cancer, breast cancer, liver cancer, gastric cancer as well as Follicular Lymphoma. Eight (8) studies were closed for recruitment; however, there are still patients on treatments or follow-ups. Eleven (11) studies were submitted to the ethics committee and pending approval. Please find the details of each study in the appendix. Twenty (20) subjects were recruited for open studies, which includes checkpoint studies. Some patients were in complete remission which excites our research team about immune-checkpoint studies. The study in collaboration with Dr. Teh Bin Tean at Duke-NUS is nearing completion and the analyzed data will be shared with us at the end of Jan 16. Our Consultants have had six (6) research papers in five (5) different journals published. Details are listed below. Alex Yuangchi Chang. The Origin of Cancer Secrets Revealed. Infinite Youth Magazine; 2015; 5:12-13. Alex Y Chang and Xu Xiao Ying: Brain Metastases From Breast Cancer and Response to Treatment With Eribulin: A Case Series. Breast Cancer (Auckl) 24 May 2015;9 19-24. Verma A, Lim AY, Tai DY, Goh SK, Kor AC, A DB, A, Abisheganaden J. Timeliness of Diagnosing Lung Cancer: Number of Procedures and Time Needed to Establish Diagnosis: Being Right the First Time. Medicine (Baltimore). 2015 Jul;94(29):e1216. doi:10.1097/md.0000000000001216. PubMed PMID: 26200646. Akash Verma MRCP, Akhil MD, Albert Y H Lim MRCP, Dessmon Y H Tai FCCP, Soon Keng Goh FRCP, Ai Ching Kor MRCP, Benjamin Ho FCCP, Dokeu Basheer AA FRCS, Yeo Wee Lee MRCP, John Abisheganaden FRCP (2015) Timeliness of In Hospital Journey of Suspected Lung Cancer Patients: From First Presentation-to-Start of Therapy. Int J Cancer Research and Molecular Mechanisms 1(1):http://dx.doi.org/10.16966/ijcrmm.102 Anthony B. El-Khoueiry, Ignacio Melero, Todd S. Crocenzi, Theodore Hobart Welling, Thomas Cheung Yau, Winnie Yeo, Akhil, Joseph Grosso, Lixin Lang, Jeffrey Anderson, Christine Marie Dela Cruz, Bruno Sangro. Phase I/II safety and antitumor 2
activity of nivolumab in patients with advanced hepatocellular carcinoma (HCC): CA209-040. J Clin Oncol 33, 2015 (suppl; abstr LBA101) Akhil, Gilberto Lopes, Lavina D. Bharwani, Chung Yip Chan, Alexander Chung, Peng Chung Cheow, Choon Kiat Ho, Kui Hin Liau, Winston Woon, Jee Keem Low, Alex Yuang-Chi Chang. Recurrence-free survival results from a pilot study of adjuvant gefitinib in resected hepatocellular carcinoma (HCC). J Clin Oncol 33, 2015 (suppl 3; abstr 404) Lastly, we are proud to announce we have received SGD 838,058.00 in research funding as of 31 Dec 2015. With the current open studies, soon to be activated studies, as well as studies on the horizon, the research team is looking forward to another busy and exciting year. Sincerely, Research Nurse Manager Xu Xiaoying 3
APPENDIX: 1. Protocol title The study to compare the the safety and efficacy of Lapatinib plus Transtuzumab plus an aromatase Inhibitor (AI) versus transtuzumab plus an AI versus lapatinib plus an AI as first- or second-line therapy in postmenopausal subjects with hormone receptor positive, HER2-positive MBC who have received trastuzumab and endocrine therapies Principle Investigator Bharwani Indication Postmenopaus al, HER2- positive metastatic Breast cancer Status during 2014 2. A Study of Neratinib plus Capecitabine versus Lapatinib plus Capecitabine in patients with HER2+ metastatic breast cancer who have received two or more prior HER2-directed regimens in the metastatic setting Bharwani HER2-positive metastatic Breast cancer failure 2 lines of treatments 3. A Phase 3 Randomized, Placebo-Controlled Trial of Carboplatin and Paclitaxel With or Without the PARP Inhibitor Veliparib (ABT-888) in HER2- Negative Metastatic or Locally Advanced Unresectable BRCA-Associated Breast Cancer Yeap Advanced Unresectable BRCA- Associated Breast Cancer 4. A multicenter, randomized, double-blind Phase 3 study of Palbociclib (Oral CDK 4/6 inhibitor) plus letrozole versus placebo plus letrozole for the treatment of previously untreated east Asian postmenopausal women with ER (+), HER2 (-) advanced breast cancer [A5481027] Chia Untreated east Asia postmenopaus al women with ER (+), HER2 (- ) 5. A Phase II, Non-comparative, label, Multicentre, International Study of MEDI4736, in Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer (Stage IIIB-IV) who have received at least Two Prior Systemic Treatment Regimens Including One Platinum based Chemotherapy Regimen (ATLANTIC) NSCLC failure 2 lines of treatment 6. A Phase III, label, Randomised, Multi-centre, International Study of MEDI4736, given as monotherapy or in combination with Tremelimumab determined by PD-L1 expression versus Standard of Care in Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer (Stage IIIB-IV) Who Have Received at Least Two Prior Systemic Treatment Regimens Including One Platinum-based Chemotherapy Regimen and Do Not Have Known EGFR TK Activating Mutations or ALK Rearrangements (ARCTIC) NSCLC failed 2 lines of treatment 4
7. A Phase III, Randomised, Double-blind, Placebocontrolled, Multi-centre, International Study of MEDI4736 as Sequential Therapy in Patients with Locally Advanced, Unresectable Non-Small Cell Lung Cancer (Stage III) Who Have Not Progressed Following Definitive, Platinum-based, Concurrent Chemoradiation Therapy (PACIFIC) Maintenance immunotherap y for NSCLC patients after Cheomoradiati on 8. A Randomized, Double-Blind Phase 2 Study of JAK Inhibitor or Placebo in Combination With Pemetrexed/Cisplatin and Pemetrexed Maintenance for Initial Treatment of Subjects With Nonsquamous, Non Small Cell Lung Cancer That Is Stage IIIB With Pleural/Pericardial Effusion, Stage IV, or Recurrent. Chia 1 st line NSCLC 9. 10. 11. 12. 13. 14. 15. 16. A Phase 2, multicenter, randomized, double-blind study of ficlatuzumab plus erlotinib versus placebo plus erlotinib in subjects who have previously untreated metastatic, EGFR-mutated non-small cell lung cancer (NCSLC) and BDX004 Poor Label A phase 1b open-label clinical trial of once daily oral treatment of afatinib plus weekly intraveneous infusion of BI 836845 in patients with EGFR mutant non-small cell lung cancer with progression following prior EGFR tyrosine kinase inhibitors. A Phase I Dose Escalation Study to Investigate the Safety, Immunoregulatory Activity, Pharmacokinetics, and Preliminary Antitumor Activity of Anti-Programmed-Death-1 (PD-1) Antibody (BMS-936558) in Advanced Hepatocellular Carcinoma in Subjects with or without Chronic Viral Hepatitis Protocol XL184-309: A Phase 3, Randomized, Double-blind, Controlled Study of Cabozantinib (XL184) vs Placebo in Subjects with Hepatocellular Carcinoma Who Have Received Prior Sorafenib A Single-Arm, -Label Phase 2 Study of Nivolumab (BMS-936558) in Subjects with Relapsed or Refractory Follicular Lymphoma (FL) [CA209-140] Multicenter Phase II Study of Nivolumab in Previously Treated Patients with Recurrent and Metastatic Nasopharyngeal Carcinoma A phase II (single center) study of neoadjuvant doxorubicin/cyclophosphamide followed by Eribulin chemotherapy (ACE) in operable HER2- negative breast cancer. A Phase Ib/II, Multicentre, Label, Randomised Study of BI 836845 in Combination With Enzalutamide, versus Enzalutamide alone, in Metastatic Castration-Resistant Prostate Cancer (CRPC) Following Disease Progression on Docetaxel-Based Chemotherapy Chang Chang/ 1 st line EGFR mutated Failed EGFR TKI Immunotherap y for HCC patients failed treatments Targeted therapy for HCC patients who failed Sorafenib Relapsed or Refractory Follicular Lymphoma 2 nd line and above NPC Neo-adjuvant for HER-2 negative 3 rd line Prostate 5
17. 18. MEDI4736 in combination with tremelimumab, MEDI4736 monotherapy, and tremelimumab monotherapy will be safe and demonstrate clinical activity in subjects with metastatic or recurrent gastric or gastroesophageal junction (GEJ) adenocarcinoma. Mutations of Epidermal Growth Factor Receptor in the blood of Patients with Advanced Non-Small Cell Lung Cancer Chang NSCLC Chang 2 nd and 3 rd line Sample 19. Randomized, Multicenter, Double-Blind, Phase 3 Trial Comparing the Efficacy of Ipilimumab in addidion to Paclitaxel and Carboplatin versus Placebo in addition to Paclitaxel and Carboplatin Alone in Subjects with Stage IV/Recurrent Non Small Cell Lung Cancer (NSCLC). Chang/ NSCLC Follow up 20. LUX Lung 7: A randomised phase IIb trial of afatinib versus gefitinib as first line treatment of patients with EGFR mutation positive advanced adenocarcinoma of the lung. Chang/ Yeap NSCLC Follow up 21. A Multicenter, Randomized, -Label, Phase 3 Trial to Compare the Efficacy and Safety of Lenvatinib Versus Sorafenib in First-Line Treatment of Subjects With Unresectable Hepatocellular Carcinoma Chang/ 1st line treatment for HCC patients Follow up 22. 23. 24. 25. 26. 27. 28. A Phase 2 -Label Rollover Study for subjects that have participated in an Astellas sponsored Linsitinib Trial Research Data base for women with Triple negative Breast cancer Bharwani Breast cancer A Pilot Study of Adjuvant Therapy of Gefitinib (Iressa ZD 1839) in patients with resectable HCC. Chang HCC Rollover Follow up Integrated genome and transcriptome of Human Liver Chang Liver tissue Sample Follow up and sample Sample A Randomized -Label Phase III Study of Single Agent Pembrolizumab versus Treatment of Physician s Choice Monotherapy for Metastatic Triple Negative Breast Cancer (mtnbc) Bharwani Breast cancer An -label, Randomized Phase 3 Efficacy Study of ASP8273 vs. Erlotinib or Gefitinib in First-line Treatment of Patients with Stage IIIB/IV Non-small Chang NSCLC Cell Lung Cancer Tumors with EGFR Activating Mutations (SOLAR Study) A Phase III, open-label, multicenter trial of avelumab (MSB0010718C) versus platinum based doublet as a first line treatment of recurrent or Stage IV PD L1+ non small cell lung cancer NSCLC 6
29. 30. 31. 32. 33. 34. 35. 36. A Phase III Randomized, -Label, Multi-Center, Global Study of MEDI4736 in Combination with Tremelimumab Therapy Versus Standard of Care Platinum-Based Chemotherapy in First-Line Treatment of Patients with Advanced or Metastatic Non-Small-Cell Lung Cancer (NSCLC). Blood based detection of EGFR Mutations in Non- Small Cell Lung Cancer (NSCLC) Patients A Randomized, Multi-center Phase III Study of Nivolumab versus Sorafenib as First-Line Treatment in Patients with Advanced Hepatocellular Carcinoma A Study of Safety, Tolerability, and Clinical Activity of MEDI4736 and Tremelimumab Administered as Monotherapy and in Combination to Subjects with Unresectable Hepatocellular Carcinoma A Multicentre, Randomized, -Label, Phase III Clinical Trial Of Gemcitabine And Carboplatin Followed By Epstein-Barr Virus-Specific Autologous Cytotoxic T Lymphocytes Versus Gemcitabine And Carboplatin As First Line Treatment For Advanced Nasopharyngeal Carcinoma Patients AR-V& splice variant in Asia patient with Castration resistant prostate. Gilead Protocol GS-US-370-1296: A Phase 2, Randomized, Double-blind Study of Gemcitabine and Nab-paclitaxel combined with Momelotinib in Subjects with Untreated Metastatic Pancreatic Ductal Adenocarcinoma Preceded by a Dose-finding, Lead-in Phase A Randomized -label Phase III Study of Single Agent Pembrolizumab vs Physicians' Choice of Single Agent Paclitaxel or Docetaxel in Subjects with Advanced/Metastatic Squamous Cancer and Adenocarcinomas of the Esophagus that have Progressed after First-Line Standard Therapy (KEYNOTE-181) Chia Non-squamous NSCLC NSCLC HCC HCC NPC Prostate Cancer Pancreatic Cancer Esophageal Cancer 7