Cancer research and cooperative groups: LACOG experience. Gustavo Werutsky LACOG Scientific Director

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1 Cancer research and cooperative groups: LACOG experience Gustavo Werutsky LACOG Scientific Director

2 Globalization of Clinical Research Clinical Studies Outside USA rug Information Association Source: Office of the Inspector General Analysis of Applications Approved by FDA in FY2008

3 Globalization of Clinical Research Density of actively recruiting clinical sites of biopharmaceutical clinical trials worldwide Thiers FA. Nature Reviews Drug Discovery. 2008; 7: 13-14

4 Principles of Cooperative Group Trials Screening, diagnosticand prevention strategies Multi-modality regimens (e.g. Surgery, Radiotherapy) Therapies for rare cancers Integration of new agents into standard regimens Combinations of novel agents developed by different sponsors Different treatment approaches already approved for clinical care Optimal duration and dose of drugs & radiotherapy

5 Cooperative Groups Worldwide

6 Cooperative Groups - Years of Existence

7 Practice Changing Clinical Trials

8 Achievements -US Cooperative Groups Over 30 Practice-Changing Clinical Trials including therapeutic agents and other modalities, with 4 announced in first 6 months of 2011 ACOSOG-Z0011 Surgery: SLND not inferior to Axillary Dissection in SLN+ BC NCIC-CTG MA.20 RT: Regional Nodal RT reduces LR & improves DFS in Node+ BC COG-AALL0232 Pediatrics: High Dose MTX improves EFS in pediatric ALL RTOG Multimodality: Short-term ADT with RT improves OS in prostate cancer Over 10 FDA Indications - New Oncology Agents (Yr FDA Approval) Bevacizumab CRC (2006); NSCLC (2006); Renal Cell Cancer (2009) Imatinib mesylate Pediatric CML (2006); Adjuvant GIST (2008) Nelarabine T-ALL and T-LBL (2005) Rituximab Diffuse Large B-cell Lymphoma (2006); Follicular NHL (2006) Trastuzumab - Adjuvant Therapy for Early-stage Her2+ Breast Cancer (2006) Thalidomide Newly Diagnosed Multiple Myeloma (2006) Anti-GD2 Antibody (ch14.18) in Neuroblastoma (BLA Currently in Preparation) Examples: New Indications Generic Agents (Yr Publication/Press Release) Daunorubicin in AML (2009); Dexamethasone in Multiple Myeloma (2007)

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10 History and Aims Was founded in 2008 by medical oncologists from several Latin American (LA) countries Is a non-profit organization and legal entity for academic cancer research in LA To build a network of LA investigators in oncology To develop and coordinate epidemiologic and clinical research in cancer in order to improve treatments and outcomes for patients

11 LACOG Structure LACOG Board Administrative Board Executive Directory Fiscal Affairs Committee LACOG Member's Assembly LACOG Executive Committee LACOG Advisory Council LACOG Coordinating Office Project Manager Laura Voelcker Pharmacovigilanceand Clinical Trial Assistant Bruno Vivan Scientific Director Gustavo Werutsky Monitoring and Data Manager Carolina Santos Statistician Jeovanny Martínez Mesa

12 Members 47 members 39 sites 10 countries Mexico N=2 Panama N=1 Colombia N=1 Ecuador N=1 Venezuela N=1 Peru N=5 Brazil N=17 Chile N=2 Argentina N=9

13 LACOG Members Characteristics (%) % 55.3% 41.1% 58.9% % 22.5% 5.0% 26.3% 10.5% 2.6% 5.3% Type of Center Number of Beds Affiliated to an University

14 Potential for Accrual LACOG Members Institutions Number of new cases per month =7001 Breast Prostate Colorrectal: Lung Skin Stomach Cervix Head and Neck 173 Uterus 204 LNH Sarcoma Melanoma Larynx Brain Thyroid 213 Kidney Esophagus Pancreas Leukemia 307 Hepatic LH Mieloma

15 Clinical Trial Development MEMBERS INVESTIGATORS COORDINATING OFFICE MULTICENTER CLINICAL TRIAL Idea Concept Protocol Accrual Results Principal Investigator Cooperative Group Disease Committee Intergroup

16 Ongoing Studies Study Number GLICO 0801 GLICO 0111 LACOG 0211 LACOG 0112 Sponsor Study Design Population/Setting Status LACOG (support GSK) Massachusetts General Hospital INCA LACOG PhaseII, randomized, capecitabine/lapatinib, vinorelbine/lapatinib, gemcitabine/lapatinib Retrospective, translational, gene signature Epidemiologic, translational, EML4-ALK fusion Systematicreview and data collection, transversal study Metastatic breast cancer HER2+ Metastatic breast cancer, HR+ Non-small cell lung cancer Regulatory process for clinical trials in Latin America Finishedaccrual Dec 2012 Regulatory process Regulatory process Ongoing

17 OngoingStudies Study Number LACOG 0212 LACOG 0312 LACOG 0113 Sponsor Study Design Population/Setting Status LACOG (Support Novartis) Novartis LACOG (Support Pfizer) Epidemiologic, LA Cancer Care project Phase II, single arm, BKM/Letrozole Phase II, single arm, Axitinib Breast Cancer Treatment Metastatic breast cancer endocrine resistance Non-clear cell renal cancer 1 st line Protocol under development May 2013 Protocol under development May 2013 Outline approved March 2013 Budgetunder discussion

18 Potential Studies EORTC Male Breast Cancer Phase III trial in Post NeoadjuvantBreast Cancer Phase III trial in Folicular Lymphoma Phase III trial in M0 Prostate Cancer

19 Partnerships Educational Research Development

20 Challenges Patient Information Regulatory Process Investment

21 Events STAT COURSE November, São Paulo-Brazil

22 Way forward Organization Investment Culture of Cooperation Education Structure

23 Thank you

24 Epidemiologic Studies MGH-International Breast Cancer Collaborative Project: Determination of an Endocrine Responsive Metastatic Breast Cancer Signature (GLICO 0111) HR+ Breast Cancer FFPE tumor block primary and metastic breast cancer Pilot study 75 patients 300 patients Demographic data Initial stage at diagnosis Treatment Relapse/progression Primary Objective: HOXB13:IL17BR gene expression Status: Recruiting Countries: Argentina, Brazil, Peru, Mexico Sponsor: MGH

25 Epidemiologic Studies Clinical and epidemiologic study of EML4-ALK e and others ALK gene fusions in patients with lung cancer in Latin America (LACOG 0211) NSCLC, subtype non-squamous, stage TNM III or IV Diagnostic and treatment of disease, in the last 5 years in selected sites 1154 patients Age on first diagnosis Ethnicity Tabagism Treatment history Histology type Stage (III or IV) Primary objective: prevalence of EML4-ALK gene fusions Status: Regulatory process Countries: Argentina, Brazil, Colombia, Mexico, Peru Sponsor: INCA (Funding Pfizer)

26 Epidemiologic Studies Latin American Cancer Care Platform Breast Cancer Study (LACOG 0312) Prospective study Newly diagnosed invasive BC Any BC TNM stage Record of tumor block N= 1500 pts Pilot phase Clinical data and biological material registration 2 nd Part Follow-up Once a year availability Objective: to sociodemographic characteristics and patterns of care and treatment of breast cancer in LA Status: Protocol development Countries: All LACOG Members Sponsor: LACOG (Funding Novartis)

27 Epidemiologic Studies Regulatory process and Legal aspects in Clinical Trials in Latin America (LACOG 0112) Regulatory Process Review Timeline data collection (industry and sites) Objective: To describe the regulatory process in LA Status: Ongoing Countries: All LACOG Members Sponsor: LACOG

28 Clinical Trials A randomized Open-Label, Phase II Study of Lapatinib Capecitabine or Lapatinib/Vinorelbine or Lapatinib/Gemcitabine in subjects with Her2/neu amplified metastatic breast cancer patients progressing after taxanes treatment (GLICO-0801) Metastatic breast cancer HER2+ After failure to taxane 1st or 2nd line n = 143 LAPATINIB 1250 mg CAPECITABINE 2000 mg/m 2 LAPATINIB 1250 mg NAVELBINE 25 mg/m 2 LAPATINIB 1250 mg GEMCITABINE 1000 mg/m 2 Primary objective: Overall Response Rate (ORR) Status: Completed Countries: Argentina, Brazil, Peru Sponsor: LACOG (Funding GSK)

29 Clinical Trials A phase II Trial of BKM120 in combination with Letrozole in postmenopausal women with hormone receptor positive and HER2 negative metastatic breast cancer that progressed on Letrozole (LACOG 0312) Metastatic BC that relapsed or progressed to Aormase Ihnibitor Postmenopausal HR+, HER2- N= 36 Letrozol 2,5mg + BKM MG Follow Up Objective: Progression free survival (PFS) Status: Protocol development Countries: Brazil Sponsor: Novartis