Gynecologic Cancer In InterGroup (G (GCIG) Ovarian Cancer - PowerPoint PPT Presentation

Gynecologic Cancer In InterGroup (G (GCIG) Ovarian Cancer Committee Wednesday, May 30, 2018, 1:30pm-3:00pm Palmer House Hilton, Chicago Chair: Antonio Gonzalez Co Co-Chair: Aik ikou Okamoto

Closed and Published Trials

AGO-OVAR OP.3/LION ENGOT Ov-31 Status Closed ENGOT model: A Sponsor: Philipps-Univ. Marburg Supported by the Deutsche Forschungsgemeinschaft Leading Group: AGO Study Group Final No. of patients: 650 Timelines: FPI Dec 2008; LPI Jan 2012; LPO Apr 2016; trial closing 2017 Publications: ASCO 2017 Abstract presented (Harter et al.) Practice changing results Planned publications: Manuscript provided to co-authors for review; submission is planned soon Planned substudies: tbd

ICON 8B MRC Clinical Trials Unit at UCL

ICON 8B Arm 1 Arm 2 Arm 3 Weekly Weekly carbo- Standard paclitaxel paclitaxel ICON8 Progression Free Survival Total Patients N=522 N=523 N=521 Progressions 330 (63%) 335 (64%) 338 (65%) Median PFS 17.9 months 20.6 months 21.1 months Log rank (vs Arm1) p=0.45 p=0.56 HR vs Arm 1 0.92 0.94 (97.5% CI) (0.77, 1.09) (0.79, 1.12) Restricted means 24.4 months 24.9 months 25.3 months Accrual began 6 th June 2011 and ICON8 pathway closed to recruitment 28 th November 2014 • • Final recruitment figure = 1566 • UK= 1397, ANZGOG= 70, GICOM= 43, KGOG= 32, ICORG= 24 • Primary PFS analysis presented at ESMO 2017. Conclusions: although weekly dose-dense chemotherapy can be delivered successfully as first-line EOC treatment without substantial toxicity increase, it does not significantly improve PFS compared to standard 3-weekly CT. MRC Clinical Trials Unit at UCL

Ongoing Trials – status update Trial name/Group name and number Trial setting: Maintenance 1 st line with Niraparib Patients: stage IV, stage III with macroscopic RD after PDS, and Stage III after NACT and IDS regardless residual disease Study Design: ENGOT MODEL C Sponsor(s): TESARO Lead Group: GEICO (PI: A. González-Martín) Planned No. of patients: 630 (Amendment 3) End recruitment: may 2018 (646 patients)

AGO-OVAR 17 ENGOT Ov-15 Trial Study Design ENGOT model A Sponsor AGO Study Group 15 months Bevacizumab 15mg/kg q21 days = 22 cycles 1:1 Paclitaxel 175 mg/m² Carboplatin AUC5 q21 days R Bevacizumab 15mg/kg q21 days N= 900 Paclitaxel 175 mg/m² 30 months = 44 cycles Carboplatin AUC5 q21 days Strata  macroscopic residual tumor (yes vs no) No. Pts.: n = 900 planned / 927 randomized  FIGO Stage (IIB-IIIC vs IV)  Study Group First Patient In: 11-Nov-2011 Last Patient In: 06-Aug-2013 Enrolment Period: 22 months Primary PFS analysis: after 697 events (~ Q4 2018)

PAOLA-1/ ENGOT-OV25/ Sponsor(s): GINECO Planned No. of patients: 762(+24 Japan) Final No. of patients: 782 (+24 in Japan) Timeline: final PFS1 analysis : 458 events (summer 2018) End of recruitment since 31 August 2017

PAOLA-1 status (15/05/2018) Accrual 600 806 900 514 Registred pts Randomized pts 800 500 Theorical randomization curve Real curve 700 Number of patients 399 400 600 329 500 300 251 400 300 200 200 94 75 70 100 100 55 43 29 26 28 21 24 20 20 15 14 0 0 GINECO AGO De MITO GEICO AGO GOTIC BGOG MANGO NSGO Aust Next steps: ▪ Steering Committee on 2 nd of June, at ASCO ▪ Collection of all tumor blocks at investigator sites by the end of June 2018 ▪ Collection of blood samples at investigator sites by the end of September 2018 ▪ Cleaning of data in eCRF, ongoing, for PFS1 analysis expected in Q4 2018 ▪ 12th Substancial Amendment expected at the end of June/beginning of July 2018 ▪ Translational Research: discussion ongoing

AGO-OVAR OP.4 AGO-DESKTOP OVAR III ENGOT-ov20 ENGOT model A Sponsor AGO Study Group n=408 Pts with R Cytoreductive + AGO-Score A surgery N platinum- Stratification: D based Platinum-free-interval O ctx* 6-12 vs > 12 months no surgery 1st line platinum recommended M based ctx: yes vs no * Recommended platinum-based chemotherapy regimens: - carboplatin/paclitaxel - carboplatin/gemcitabine - carboplatin/pegliposomal doxorubicin - or other platinum combinations in prospective trials Status 28th March 2018 192 of 244 OS events observed First Patient in 14-Jul-2010 Interim analysis presented at ASCO 2017 Last Patient in 25-Mar-2015 OS follow-up ongoing Enrolment period 58 months Final OS analyses ~ 2019

AGO-OVAR 2.21 ENGOT ov18 ENGOT model A Sponsor AGO Study Group Bevacizumab 15mg/kg q3w until PD Gemcitabine 1000 mg/m² d1 and 8 Carboplatin AUC 4 d 1 q3w 1:1 R Bevacizumab Bevacizumab 15mg/kg q3w until PD 10mg/kg q2w Pegylated Liposomal Doxorubicin 30 mg/m² d1 Carboplatin AUC 5 d1 q4w Stratification Factors No. pts : 654 planned/ 682 randomized ❖ Platinum free interval (6-12 months vs. > 12 months) First Patient In: 01-Aug-2013 ❖ In case of debulking surgery for recurrence: residual tumour (yes vs. no) Last Patient In: 31-Jul-2015 In case of no debulking surgery for recurrence: all pts. Enrolment Period: 24 months categorized to residual tumor = yes ❖ prior antiangiogenetic treatment (yes vs. no) Primary PFS analysis: Events reached; primary PFS analysis ❖ group language is ongoing; Abstract submitted to ESMO 2018

Closed Trial – status update MITO 16b; MANGO-OV2b ENGOT Ov-17 A multicenter phase III randomized study with second line chemotherapy ± bevacizumab in patients with platinum sensitive epithelial ovarian cancer recurrence after a bevacizumab/chemotherapy first line GROUP N. Patients Non profit Sponsor: NCI Naples MITO 206 Lead groups: MITO MaNGO GINECO 100 Final No. of patients: 406 MANGO 72 Timeline: FPI: 12/2013 LPI: SAKK 17 11/2016 HeCOG 11 Primary results: ASCO 2018 oral session BGOG 0 Translational: Q4 2018 Total 406

Closed Trial – status update MITO 8; ENGOT Ov-1 A phase III international multicenter 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 Enrollment by Group Nonprofit Sponsor: NCI Naples , MITO lead Final No. of patients: 215 GROUP N. Patients Timeline : FPI 1/2009 LPI 10/2015 MITO 170 Publications: Primary results MANGO 20 1. J Clin Oncol. 2017 Oct 10;35(29):3347-3353. BGOG 13 Epub AGO 12 2. QOL: Ann Oncol. 2018 Feb 16. doi: Total 215 10.1093/annonc/mdy062.

INOVATYON Phase III international, randomised study of Trabected tedin plus Pegylated ted Liposo somal Doxorub rubicin (PLD) versus rsus Carboplati tin plus PLD in patients with relapsed ovarian cancer progressing within 6 – 12 months of last platinum At PD, subsequent Group up A: therapy at investigator PLD 30 mg/m² + discretion Carboplatin AUC 5 Relapsed partially q4 wks platinum sensitive Ovarian Cancer R after end of 1 st or Up to 6 cycles or PD (1:1) 2 nd -line platinum therapy Group up B: At PD, subsequent PLD 30 mg/m 2 + platinu num rech challe alleng nge is Trabectedin1.1 mg/m 2 mandat atory ry q3wks RECIST tumor evaluation at 12 and 24 weeks Primary ary Endpo poin int: Overall Survival Primary ary analysis ysis: Intention to treat ,442 events/588 588 patients

INOVATYON Phase III international, randomised study of Trabected tedin plus Pegylate ted Liposo osomal Doxorub ubicin (PLD) versus sus Carboplati tin plus PLD in patients with relapsed ovarian cancer progressing within 6 – 12 months of last platinum Accr ccrual ual closed losed Sept Septembe ember 2017 2017 25 5 117 enrolling sites/ 618 patients overall 15 25 25 Next steps: 10 58 Second ond Interim rim Analys ysis is 22 42 Septem tember2018 ber2018 283 Final Analysis ~ July-August 108 2020