A JOHNS HOPKINS SINGAPORE ANNUAL RESEARCH REPORT 2016

Transcription

1 A JOHNS HOPKINS SINGAPORE ANNUAL RESEARCH REPORT 2016 The Promise of Medicine: The research team at Johns Hopkins Singapore provides unparalleled excellence in their search for ground breaking treatment options. 16 years of excellence in patient care, research, and education

2 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). The research department is staffed by seven (7) investigators, six (6) coordinators and one (1) assistant coordinator at the end of The program continues to become more robust as additional studies are added annually. This year, we have seen a spike of subject recruitments due to our continuing effort in providing excellent research and maintaining strong alliances with industry drug developers to make important scientific strides in the field of oncology. From Jan 2016 to Dec 2016, the Office of Research coordinated and managed a total of Forty-eight (48) studies as following: 22 studies were opened for recruitment. The studies examine treatments for the different types and stages of lung cancer, breast cancer, liver cancer, gastric cancer, nasopharyngeal carcinoma as well as follicular lymphoma. 14 studies were closed for recruitment. However, some studies are still having patients on treatments or follow-up and other studies are having data analysis ongoing. 5 studies terminated/completed. 7 studies submitted to the ethics committee and pending approval. We also created Johns Hopkins Singapore Cancer Database. Please find the details of each study in the appendix. 55 subjects were recruited for the therapeutic studies during the past 1 year. We have seen many good responses from especially targeted therapies and immunotherapy studies. 23 subjects were recruited for blood draw studies, one is to study the concordance of genetic mutations between blood and tumor samples and the other is to study the circulation tumor cells in blood. Those studies will make genetic diagnosis less invasive in future. Our Consultants had 7 research papers/ abstracts published in different journals as below: 2

3 Chang AY-C, Foo KF, Koo W-H, et al. Phase II study of neo-adjuvant chemotherapy for locally advanced gastric cancer. BMJ Gastro 2016;3: e Ng CC, Chen FX and Chang A. New Paradigms in the Management of Brain Metastases from Non-Small Cell Lung Cancer (NSCLC). In: Horizons in Cancer Research, Volume 63. Hiroto S. W (ed), Nova Science Publishers, Inc., NY 2016, chapter 1 Alex Yuangchi Chang. Understanding Cancer Prevention. Infinite Youth Magazine; 2016; 12: Rucha S Dagaonkar, Caroline V Choong, Atasha Binti Asmat, Dokeu Basheer A Ahmed, Akhil Chopra, Albert Y H Lim, Dessmon Y H Tai, Ai Ching Kor, Soon Keng Goh, John Abisheganaden, Akash Verma. Significance of coexistent granulomatous inflammation and lung cancer J Clin Pathol jclinpath Published Online First: 19 September 2016 doi: /jclinpath Verma A, Chopra A, Lee YW, Bharwani LD, Asmat AB, Dokeu Basheer AA, Akbar FA, Lim AY, Chotirmall SH, Abisheganaden J. Can EGFR-Tyrosine Kinase Inhibitors (TKI) Alone Without Talc Pleurodesis Prevent Recurrence of Malignant Pleural Effusion (MPE) in Lung Adenocarcinoma. Curr Drug Discov Technol May 24 Finkelstein E, Malhotra C, Chay J, Chopra A, Kanesvaran R, Ozdemir S. Impact of treatment subsidies and cash pay-outs on treatment choices at the end of life. Value in Health (Accepted for publication on February 19, 2016) Anthony B. El-Khoueiry, Bruno Sangro, Thomas Cheung Yau, Todd S. Crocenzi, Theodore Hobart Welling, Winnie Yeo, Akhil Chopra, Jeffrey Anderson, Christine Marie Dela Cruz, Lixin Lang, Jaclyn Neely, Ignacio Melero. Phase I/II safety and antitumor activity of nivolumab (nivo) in patients (pts) with advanced hepatocellular carcinoma (HCC): Interim analysis of the CheckMate-040 dose escalation study. J Clin Oncol 34, 2016 (suppl; abstr 4012) In term of research funding, we have secured more than 1.3 million from pharmaceuticals and Santa Fe Relocation Services Pte Ltd to support the research activities for pharmaceutical studies as well as investigator initiated breast studies. The office of Research will continue their effort in the coming new year! Research Nurse Manager Xu Xiaoying 3

4 APPENDIX: 1. Protocol title 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 Principle Investigator Bharwani Indication HER2-positive metastatic Breast cancer failure 2 lines of treatments Status 2. 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 Chia Advanced Unresectable BRCA-Associated Breast Cancer 3. 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 [A ] Chia Untreated east Asia postmenopausal women with ER (+), HER2 (-) 4. A Randomized -Label Phase III Study of Single Agent Pembrolizumab versus Treatment of Physician s Choice Monotherapy for Metastatic Triple Negative Breast Cancer (mtnbc) 5. A multicentre, phase 1B/2 study of Varlitinib in combination with Gemcitabine and Cisplatin for treatment naïve advanced or metastatic biliary tract cancer. 6. A phase 1b open-label clinical trial of once daily oral treatment of afatinib plus weekly intraveneous infusion of BI in patients with EGFR mutant non-small cell lung cancer with progression following prior EGFR tyrosine kinase inhibitors. Bharwani 2 nd and 3 rd line Breast cancer Chang 1 st line Biliary tract cancer Chopra Failed EGFR TKI for patient failed afatinib only 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 Cell Lung Cancer Tumors with EGFR Activating Mutations (SOLAR Study) A Phase III, open-label, multicenter trial of avelumab (MSB C) versus platinum based doublet as a first line treatment of recurrent or Stage IV PD L1+ non-small cell lung cancer 4 Chang NSCLC Chopra NSCLC

5 9. 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 (NEPTUNE). Chopra Non-squamous NSCLC Blood based detection of T790 mutation in lung cancer specimen of patients with known activating EGFR mutations who have progressed on first line TKI therapy. Impact of EGFR mutation status on the survival of patients with advanced non-small cell lung cancer and brain metastases Chopra NSCLC Chopra NSCLC 12. Analytical validation of ClearCell FX for clinical application in personalized medicine Bharwani NSCLC, Prostate, HCC 13. A Randomized, Multi-center Phase III Study of Nivolumab versus Sorafenib as First-Line Treatment in Patients with Advanced Hepatocellular Carcinoma Chopra 1 st Line HCC 14. Protocol XL : A Phase 3, Randomized, Double-blind, Controlled Study of Cabozantinib (XL184) vs Placebo in Subjects with Hepatocellular Carcinoma Who Have Received Prior Sorafenib Chopra Targeted therapy for HCC patients who failed Sorafenib 15. A Study of Safety, Tolerability, and Clinical Activity of MEDI4736 and Tremelimumab Administered as Monotherapy and in Combination to Subjects with Unresectable Hepatocellular Carcinoma 16. 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 NPC patients. 17. A Phase Ib/II, Multicentre, Label, Randomised Study of BI in Combination With Enzalutamide, versus Enzalutamide alone, in Metastatic Castration-Resistant Prostate Cancer (CRPC) Following Disease Progression on Docetaxel-Based Chemotherapy Chopra 2 nd line HCC, recruitment by cohort. Chopra 1 st line NPC Chopra 3 rd line Prostate for recruitment till Mar 2016, still having patient on treatment. 5

6 18. 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) Chopra/ Samol 2 nd line esophageal 19. Johns Hopkins Singapore Cancer Database Chang All Cancer 20. An -label Randomized Multinational Phase 3 Trial of Nivolumab versus Docetaxel in Previously Treated Subjects with Advanced or Metastatic Non-small Cell Lung Cancer [CA209078] Chia 2 nd Line NSCLC for recruitment till early 2016, still having patient on follow up. 21. Retrospective Review of Asian patients receiving Eribulin for Metastatic breast cancer pretreated with several chemotherapy regimen including an anthracycline and a taxane Bharwani Chart review: Breast Cancer patient received Eribulin JHS. for 22. A Phase 2, multicenter, randomized, doubleblind 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 Chang 1 st line EGFR mutated till early Sponsor discontinue d the study. 23. 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 Bharwani Postmenopausal, HER2-positive metastatic Breast cancer Follow up 24. LUX Breast 1: An open label, randomised phase III trial of BIBW 2992 and vinorelbine versus trastuzumab and vinorelbine in patients with metastatic HER2 breast cancer failing one prior trastuzumab treatment Bharwani 2 nd line, her 2 positive Follow up 25. Research Data base for women with Triple negative Breast cancer Bharwani Triple negative, blood draw study Sample with Dr Park for analysis. 6

7 26. 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) 27. A Phase III, label, Randomised, Multicentre, 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) Chopra NSCLC failure 2 lines of treatment Chopra NSCLC failed 2 lines of treatment Closed recruit, subjects on treatment and follow up. Closed recruit, subjects on treatment 28. 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, Platinumbased, Concurrent Chemoradiation Therapy (PACIFIC) Chopra Maintenance immunotherapy for NSCLC patients after Cheomoradiation Closed recruit, subjects on treatment 29. Multicenter Phase II Study of Nivolumab in Previously Treated Patients with Recurrent and Metastatic Nasopharyngeal Carcinoma 30. Mutations of Epidermal Growth Factor Receptor in the blood of Patients with Advanced Non-Small Cell Lung Cancer 31.. 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) 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. Chopra 2 nd line and above NPC Closed for recruitment. Still have patient on treatment. Chang NSCLC Writing study report. Chang/ Chopra NSCLC Completed in Chang NSCLC Follow up 7

8 33. A Phase 2 -Label Rollover Study for subjects that have participated in an Astellas sponsored Linsitinib Trial Chopra Rollover Terminated in Jun 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/ Chopra 1st line treatment for HCC patients Follow up 35. A Pilot Study of Adjuvant Therapy of Gefitinib (Iressa ZD 1839) in patients with resectable HCC. 36. Integrated genome and transcriptome analysis of Human Liver 37. 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. 38. 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 ) in Advanced Hepatocellular Carcinoma in Subjects with or without Chronic Viral Hepatitis Chang HCC Follow up and sample analysis Chang Liver tissue Sample analysis Chang 2 nd and 3 rd line Recruitment on hold due to data analysis in Reopen in Chang/ Chopra Immunotherapy Follow up for HCC patients failed treatments 39. A Phase 2, multicenter, randomized, doubleblind 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 Chang 1 st line EGFR mutated Terminated in ELUXA 2: An international, randomised, multicentre, active controlled, open-label Phase III study evaluating the efficacy of BI versus standard platinum doublet chemotherapy in patients with T790M-positive locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease progressed on one epidermal growth factor receptortyrosine kinase inhibitor (EGFR-TKI) treatment. Chopra 2 nd line, NSCLC Sponsor decided to terminate due to change in IP developmen t plan. 8

9 41. Boehringer Ingelheim, ELUXA 3 An international, randomised, multi-centre, activecontrolled, open-label Phase III study evaluating the efficacy of BI versus afatinib as first line treatment in patients with locally advanced or metastatic non-small cell lung cancer carrying epidermal growth factor receptor activating mutations. 42. AR-V& splice variant in Asia patient with Castration resistant prostate. 43. A Pilot study of Eribulin in Breast Cancer (BC) Patients with Brain Metastases Previously Treated with Anthracyclines and Taxanes. Chopra 1 st line, NSCLC Sponsor decided to terminate due to change in IP developmen t plan. Chopra Prostate Cancer Pending Wong BMBC Pending 44. Genomic Analysis of Lung Cancer Chopra NSCLC Pending 45. Johns Hopkins Breast Cancer Program Longitudinal Repository 46. An open-label, multicenter, Phase IIIb study to assess the safety of ribociclib (LEE011) in combination with letrozole for the treatment of postmenopausal women with hormone receptor-positive (HR+) HER2-negative (HER2-) advanced breast cancer (ABC) with no prior hormonal therapy for advanced disease 47. Randomised phase 2 study of nivolumab versus nivolumab and ipilimumab combination in EGFR mutant Non-small Cell Lung Cancer Bharwani Breast cancer repository Bharwani Bharwani Breast cancer NSCLC Pending (DSRB enquiry of blood draw) Pending Pending 48. -Label, Randomized Trial of Nivolumab (BMS ) plus Pemetrexed/Platinum or Nivolumab plus Ipilimumab (BMS ) vs Pemetrexed plus Platinum in Stage IV or Recurrent Non-Small Cell Lung Cancer (NSCLC) Subjects with Epidermal Growth Factor Receptor (EGFR) Mutation, T790M Negative Who Failed 1L EGFR Tyrosine Kinase Inhibitor Therapy Chang NSCLC Pending 9