Tarceva Trial EORTC 55041

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3 Tarceva Trial EORTC Primary Chemotherapy Tarceva consolidation 2 years Control Patients closed / 835 Leading Participating EORTC AGO-AUSTRIA, ANZGOG, GINECO, MRC/NCIC, MANGO

4 Randomised trial on Erlotinib vs observation in first-line ovarian cancer: Progression-free survival Median PFS: Erlotinib: 12,7 months Observation: 12,4 months PRESENTED BY: Ignace Vergote

5 HECTOR Carbo Topo vs Chemo (CT or CG) in recurrent Platinum-sensitive ovarian cancer Patients closed 550 Leading Participating NOGGO/AGO-OVAR AGO-AUSTRIA, GEICO

6 Results (Primary objective)

7 Aurelia Platinum resistant OC Chemo + Bevacizumab Chemo Leading Participating GINECO AGO, GEICO, NSGO, MITO, BGOG, DGOG, HECOG,

8 Estimated probability Progression-free survival CT (n=182) BEV + CT (n=179) Events, n (%) 166 (91%) 135 (75%) Median PFS, months (95% CI) HR (unadjusted) (95% CI) Log-rank p-value (2-sided, unadjusted) 3.4 ( ) 0.48 ( ) < ( ) 0.2 No. at risk: CT BEV + CT Time (months) Median duration of follow-up: 13.9 months (CT arm) vs 13.0 months (BEV + CT arm)

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11 AGO-OVAR 12 Carbo Paclitaxel +/- BIBF 1120 (Vargatef) Patients closed 1366 (7/2011) Leading AGO-OVAR Participating AGO-Austria, BGOG, GINECO, MANGO, MITO, NSGO, US Oncology

12 AGO-OVAR 16 Pazopanib Primary chemotherapy Placebo Patients closed 941 (8/2010) Leading AGO-OVAR Participating AGO-Austria, ANZGOG, BGOG, GEICO, GINECO, ICORG, JGOG,KGOG, MANGO, MITO, NSGO, NYCC, California Consortium

13 AGO-OVAR OP.3 (LION) FIGO IIB-IV, complete resection Patients closed 640 (2/12) Leading AGO-OVAR Systematic LNE Observation Participating AGO-Austria, ANZGOG, BGOG, KGOG, MaNGO, MITO,

14 ICON6 A Randomised Trial of Concurrent Cediranib (with Platinum-based Chemotherapy) and Maintenance Cediranib in Women with Platinum-Sensitive Relapsed Ovarian Cancer Closed 12/2011 Target accrual: 486 pts

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16 AGO-OVAR 17 Study design 1:1 Bevacizumab 15mg/kg q21 Paclitaxel 175 mg/m² Carboplatin AUC5 q21 Tage 15 months = 22 cycles R N= 900 Strata Residual disease (yes vs no) FIGO stage (IIB-III vs IV) Center Bevacizumab 15mg/kg q21 Paclitaxel 175 mg/m² Carboplatin AUC5 q21 Tage 30 months = 44 cycles Primary endpoint: PFS Sec. endpoints: RR, OS, QoL, Safety LKP: Prof. J. Pfisterer

17 AGO-OVAR DESKTOP III (Protocol AGO - OVAR OP.4) A randomized trial evaluating cytoreductive surgery in patients with platinum-sensitive recurrent ovarian cancer 408 Pts with + AGO-Score Stratification: Platinum-free-interval 6-12 vs > 12 months 1st line platinum based ctx: yes vs no R A N D O M Recruitment: 124 pts ( ) Cytoreductive surgery no surgery platinum-based chemotherapy* recommended * Recommended platinum-based chemotherapy regimens: - carboplatin/paclitaxel - carboplatin/gemcitabine - carboplatin/pegliposomal doxorubicin -or other platinum combinations in prospective trials

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19 Avastin and weekly paclitaxel use in sex cord-stromal ovarian tumors A randomized, open label, phase II trial of bevacizumab plus weekly paclitaxel followed by maintenance with bevacizumab monotherapy versus weekly paclitaxel followed by observation in patients with relapsed ovarian sex-cord stromal tumors 19

20 Sandro Pignata

21 GCIG Leiden Status Report of: MITO-7 MITO-8 MITO-11 MITO-12 MITO-16 Trials S. Pignata Istituto Nazionale Tumori Napoli

22 MITO 7 ENGOT-OV10 WEEKLY vs EVERY 3 WEEK CARBOPLATIN + PACLITAXEL IN PATIENTS WITH OVARIAN CANCER: RANDOMIZED MULTICENTRE STUDY

23 MITO 8 ENGOT-OV1 A PHASE III INTERNATIONAL MULTICENTRE RANDOMIZED STUDY TESTING THE EFFECT ON SURVIVAL OF PROLONGING PLATINUM-FREE INTERVAL IN PATIENTS WITH OVARIAN CANCER RECURRING BETWEEN 6 AND 12 MONTHS AFTER PREVIOUS PLATINUM BASED CHEMOTHERAPY

24 MITO 12 ENGOT OV-12 PATHWAY TO DIAGNOSIS OF OVARIAN CANCER: OBSERVATIONAL RETROSPECTIVE MULTICENTERED STUDY

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26 GOG0252: IP Therapy Epithelial Ovarian, Fallopian, or Primary Peritoneal Cancer Optimal and Suboptimal Disease (through April 2011) Primary Endpoint: PFS IV Carbo I Carboplatin AUC=6 (IV) Paclitaxel 80 mg/m 2 IV (d1,8,15) Bevacizumab (C2-6) Bevacizumab q21d x 16 IP Carbo II Carboplatin AUC=6 (IP) Paclitaxel 80 mg/m 2 (d1,8,15) Bevacizumab (C2-6) Bevacizumab q21d x 16 IP Cisplatin III Cisplatin 75 mg/m 2 (IP) Paclitaxel 135 mg/m 2 (d1, 3h) Paclitaxel 60 mg/m 2 (d8, IP) Bevacizumab (C2-6) Bevacizumab q21d x 16 Open: 27-Jun-2009 Closed: 29-Oct-2011 Accrual: 1560 pts (250 suboptimal) Walker J. for GOG, pending

27 GOG0262: Dose-Dense Integration Epithelial Ovarian, Fallopian, or Primary Peritoneal Cancer Suboptimal residual disease, amended to permit NACT-ICS Primary Endpoint: PFS Incorporation of early perfusion-based CT imaging (ACRIN 6695) I Carboplatin AUC=6 Paclitaxel 80 mg/m 2 (d1,8,15) +/- Bevacizumab (C2-6) $ Bevacizumab q21d $ II Carboplatin AUC=6 Paclitaxel 175 mg/m 2 (d1) +/- Bevacizumab (C2-6) $ Bevacizumab q21d $ $ Use of Bevacizumab to be determined by patient and physician choice prior to randomization Open: 27-SEP-2010 Closed: 08-FEB-2012 (accrual to imaging ongoing) Target Accrual: 700 pts (with imaging) Chan J. for GOG, pending

28 GOG0273: Elderly Patients Epithelial Ovarian, Fallopian, or Primary Peritoneal Cancer Clinical Stage I-IV, PS 0-3, Elect PCS or NACT-ICS Elect single-agent or combination chemotherapy with PKs Age >70 with no more than 25% age <75 Primary Endpoints: Completion of 4 cycles without DLT and impact of IADL score on treatment I Carboplatin AUC=5 Paclitaxel 135 mg/m 2 (d1) G-CSF x4 Optional ICS Optional ChemoRx II Carboplatin AUC=5 x4 Open: 15-AUG-2011 Closed: Target Accrual: 185 pts Von Gruenigen V. for GOG, pending

29 Phase I GOG9923: Treatment Regimens Regimen I (Phase A) - Continuous Paclitaxel 175 mg/m 2 IV, Day 1 Carboplatin AUC 6 IV, Day 1 Bevacizumab 15 mg/kg IV, Day 1 * ABT-888 twice daily, Days 1-21** Regimen II (Phase A) - Continuous Paclitaxel 80 mg/m 2 IV, Days 1,8,15 Carboplatin AUC 6 IV, Day 1 Bevacizumab 15 mg/kg IV, Day 1 * ABT-888 twice daily, Days 1-21** Regimen I (Phase A) - Intermittent Paclitaxel 175 mg/m 2 IV, Day 1 Carboplatin AUC 6 IV, Day 1 Bevacizumab 15 mg/kg IV, Day 1 * ABT-888 twice daily, Days -2 to 5** Regimen II (Phase A) - Intermittent Paclitaxel 80 mg/m 2 IV, Days 1,8,15 Carboplatin AUC 6 IV, Day 1 Bevacizumab 15 mg/kg IV, Day 1 * ABT-888 twice daily, Days -2 to 5** Regimen III (Phase A) - Continuous Paclitaxel 135 mg/m 2 IV, Day 1 Cisplatin 75 mg/m 2 IP, Day 1 or 2 Paclitaxel 60 mg/m 2 IP, Day 8 Bevacizumab 15 mg/kg IV, Day 1 * ABT-888 twice daily, Days 1-21** Regimen III (Phase A) - Intermittent Paclitaxel 135 mg/m 2 IV, Day 1 Cisplatin 75 mg/m 2 IP, Day 1 or 2 Paclitaxel 60 mg/m 2 IP, Day 8 Bevacizumab 15 mg/kg IV, Day 1 * ABT-888 twice daily, Days -2 to 5** *Bevacizumab started in cycle 2 and continued as maintenance for Cycles **ABT-888 will be dose escalated to determine the MTD.

30 GOG OVM1201: PCS vs NACT-ICS Epithelial Ovarian, Fallopian, or Primary Peritoneal Cancer Presumptive Stage IIIC-IV, CA125:CEA >25, PS 0-3 Primary Endpoint: Improved OS (PCS vs NACT-ICS) Secondary Endpoints: PFS, Costs, Predictive Biomarkers for Cytoreduction Secondary ACRIN Endpoint: Predictive value of perfusion CT imaging Bifactorial Randomization: Metformin vs Placebo Serial Tumor Biopsies (NACT-ICS) I PCS ChemoRx (IV or IP) x6* Metformin (concurrent and maintenance) II Bx ChemoRx (IV) x3* ICS ChemoRx (IV or IP) x3* Placebo (concurrent and maintenance) * Carboplatin AUC=6 (IV), Paclitaxel 175 mg/m 2 or Cisplatin 75 mg/m 2 (IP), Paclitaxel 135 mg/m 2 (IV) D1, 60 mg/m 2 (IP) D8 Open: JAN-2013 Closed: (Not Approved by GCSC, AUG 2012) Target Accrual: 780 pts Chi D. for GOG, pending

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32 Japan (JGOG/GOTIC) Closed Study

33 JGOG3017 Randomized Phase III Trial of Paclitaxel plus Carboplatin (TC) Therapy versus Irinotecan plus Cisplatin (CPT-P) Therapy as a First Line Chemotherapy for Clear Cell Carcinoma of the Ovary Ovarian Clear Cell Carcinoma FIGO stage Ic-Ⅳ RANDOMIZATION Paclitaxel 175 mg/m 2 IV, Day1 Carboplatin AUC 6 IV, Day1 Q21, 6 Cycles Irinotecan 60 mg/m 2 IV, Day1, 8, 15 Cisplatin 60 mg/m 2 IV, Day1 Q28, 6 Cycles Primary Endpoint: PFS Secondary Endpoint: OS, Toxicity, Response rate Accrual Goal: 662 patents

34 On-going Study

35 A Randomized Phase II/III Trial of 3 Weekly Intraperitoneal versus Intravenous Carboplatin in Combination with Intravenous Weekly Dose-Dense Paclitaxel for Newly Diagnosed Epitherial Ovarian, Fallopian Tube and Primary Peritoneal Cancer Epithelial ovarian, Fallopian tube or Primary peritoneal cancer FIGO stage II IV Including Bulky Tumor RANDOMIZATION Paclitaxel 80 mg/m 2 IV Day1,8,15 Carboplatin AUC 6 IV Q21, 6-8 Cycles Paclitaxel 80 mg/m 2 IV Day1,8,15 Carboplatin AUC 6 IP Q21, 6-8 Cycles Primary Endpoint: PFS Secondary Endpoint: OS, Toxicity, QOL Accrual Goal: 746 patents

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37 OV21, an International IP Trial A PHASE II/III STUDY OF INTRAPERITONEAL (IP) PLUS INTRAVENOUS (IV) CHEMOTHERAPY VERSUS IV CARBOPLATIN PLUS PACLITAXEL IN PATIENTS WITH EPITHELIAL OVARIAN CANCER OPTIMALLY DEBULKED AT SURGERY FOLLOWING NEOADJUVANT INTRAVENOUS CHEMOTHERAPY: A Gynecologic Cancer Intergroup (GCIG) Trial led by the NCIC CTG NCIC CTG : OV.21 NCRI: UCL08/0379 GEICO: 0902 SWOG: Activation process, 4 centres Co chairs : Helen Mackay Diane Provencher

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39 ICON8 current design Diagnosis of Stage IC-IV EOC/PPC/FTC Immediate Primary Surgery (IPS) Delayed Primary Surgery (planned) Randomise 1:1:1 Randomise 1:1:1 Arm 1 6 cycles Arm 2 6 cycles Arm 3 6 cycles Arm 1 3 cycles Arm 2 3 cycles Arm 3 3 cycles Arm 1 Carboplatin AUC 5 q3w (control) Paclitaxel 175mg/m 2 q3w Arm 2 Carboplatin AUC 5 q3w Paclitaxel 80mg/m 2 q1w Arm 3 Carboplatin AUC 2 q1w Paclitaxel 80mg/m 2 q1w Delayed Primary Surgery (DPS) Arm 1 3 cycles Cycle 3 d15 omitted Arm 2 3 cycles Arm 3 3 cycles Target sample size: 1485 over 3 years Current trial status: 282 randomised ( )

40 A GCIG Intergroup multicentre trial of open label carboplatin and paclitaxel +/- bevacizumab compared with oxaliplatin and capecitabine +/- bevacizumab as first line chemotherapy in patients with mucinous Epithelial Ovarian Cancer (meoc) For more information Cancer Research UK & UCL Cancer Trials Centre

41 Mansoor Mirza

42 NiCCC - Nintedanib in Clear Cell Cancer A Randomised Phase II Study of Nintedanib versus Chemotherapy in Recurrent Clear Cell Carcinoma of the Ovary or Endometrium SGCTG/NCRI/NSGO

43 Jim Paul

44 LOGS: A Randomized Phase II/III Study to Assess the Efficacy of MEK inhibitor GSK in Patients with Recurrent or Progressive Low-Grade Serous Ovarian Cancer or Peritoneal Cancer Chief Investigator: Charlie Gourley (UK) David Gershenson (USA)

45 Planned trials

46 Philipp Harter

47 Antonio Gonzalez

48 Jonathan Berek