NRG Oncology: Ovarian Cancer Closed: GOG0212 Front-Line - PowerPoint PPT Presentation

NRG Oncology: Ovarian Cancer Closed: • GOG0212 Front-Line Maintenance, Letter to Investigators (26-SEP-2016) • GOG0252 Front-Line IP vs IV Chemotherapy Ongoing: • GOG3005 Front-Line Chemotherapy +/- Veliparib (Treatment and Maintenance) • GOG0213 Platinum-Sensitive Recurrence, Secondary Cytoreductive Surgery • NRG GY004 Platinum-Sensitive Recurrence, Cediranib-Olaparib Phase III • NRG GY005 Platinum-Resistant Recurrence, Cediranib-Olaparib Phase III New Studies • NRG GY007 Front-Line NACT +/- Ruxolitinib JAK2i (open to accrual) • OVM 1509 Front-Line NACT +/- Pembrolizumab (pending GCSC review) • OVM 1629 Front-Line NACT +/- Metformin (U Chicago SPORE project)

GOG212: Ovarian Maintenance • Epithelial Ovarian or Primary Peritoneal Cancer • Optimal or Suboptimal Cytoreduction • Clinical CR with normal CA125, no symptoms, normal CT • Primary Carboplatin and Paclitaxel (or Docetaxel), 5-6 cycles • Primary endpoints OS and Neutotoxicity PG-Paclitaxel 175 mg/m 2 (15 m), q28d x 12 I Primary Rx: II Paclitaxel 175 mg/m 2 (3 h), q28d x 12 Carboplatin and Taxane (5-6 Cy) III Observation Open: 21-MAR-2005 Closed: 13-JAN-2014 (9 y) Target Accrual: Target 1100 pts (actual 1157) Copeland L, for NRG (pending)

GOG212: Ovarian Maintenance Letter to Investigators 26-SEP-2016: “…The NRG Oncology Data Monitoring Committee recently reviewed the results from a scheduled interim analysis and voted to release the study results early due to futility. In other words, the study results indicate it is unlikely that either of the taxane regimens significantly reduces the hazard of death when compared to no further anti-cancer treatment until disease progression…”

GOG0252: IP Therapy • Epithelial Ovarian, Fallopian, or Primary Peritoneal Cancer • Optimal and Suboptimal Disease (through April 2011) • Primary Endpoint: PFS (Analysis JAN 2016) Carboplatin AUC=6 (IV) Bevacizumab IV Carbo Paclitaxel 80 mg/m 2 IV (d1,8,15) I q21d x 16 Bevacizumab (C2-6) Carboplatin AUC=6 (IP) Bevacizumab Paclitaxel 80 mg/m 2 (d1,8,15) IP Carbo II q21d x 16 Bevacizumab (C2-6) Cisplatin 75 mg/m 2 (IP) Bevacizumab Paclitaxel 135 mg/m 2 (d1, 3h) IP Cisplatin III q21d x 16 Paclitaxel 60 mg/m 2 (d8, IP) Bevacizumab (C2-6) Open: 27-Jun-2009 Closed: 29-Oct-2011 Accrual: 1560 pts (max 250 suboptimal) Walker J. for GOG, SGO 2016

GOG0252: IP vs IV (PFS) Optimal Cytoreduction (Stage II-III) 1.0 Regimen Events Median Carboplatin (IV) + Paclitaxel (IV) 303/461 26.8 Progression-Free Survival Carboplatin (IP) + Paclitaxel (IV) 300/464 28.7 0.8 Cisplatin (IP) + Paclitaxel (IV+IP) 307/456 27.8 0.6 0.4 0.2 Regimen HR (95% CI) Logrank (2T) Carboplatin (IP) 0.947 (0.808 - 1.11) 0.416 Cisplatin (IP) 1.01 (0.858 - 1.18) 0.727 0.0 0 12 24 36 48 60 72 Months on Study Walker J. et al, SGO LBA 2016

GOG0252: IP vs IV (PFS) ITT (All Eligible Patients) Walker J. for GOG, 2016

GOG3005: PARPi Primary Therapy & Maint • High-grade extrauterine serous tumors, Stage I-C, II, III, IV • Election for NACT-ICS and scheduling of paclitaxel (no IP therapy) • Primary endpoint PFS: (1) Entire Population, (2) BRCA1/2 Population • Stratifications: Stage, Residual Disease, NACT-ICS, Region, gBRCA status Paclitaxel (standard or dose-dense) Placebo x 6 Carboplatin AUC 6 (IV)* I PO BID Placebo PO BID 1:1:1 Paclitaxel (standard or dose-dense) Placebo Carboplatin AUC 6 (IV)* II x 6 PO BID Veliparib 150 mg PO BID Paclitaxel (standard or dose-dense) Veliparib 400 mg Carboplatin AUC 6 (IV)* II x 6 PO BID Veliparib 150 mg PO BID Collaborative development with AbbVie (M13-694) including international participation, seeking EMA and FDA regulatory approval Open: JUL 2015 Closed: (ongoing) Target Accrual: ~1100 pts (264 BRCA1/2 +) Coleman R, et al. for GOG

GOG3005: PARPi Primary Therapy & Maint 1250 Projected Subjects Cumulative (Balanced) 1000 Actual Subjects Cumulative (Balanced) 750 Projected Subjects Cumulative (Aggressive) 645 500 250 Currently accruing several months ahead of original projection 0 Jul-15 Aug-15 Sep-15 Oct-15 Nov-15 Dec-15 Jan-16 Feb-16 Mar-16 Apr-16 May-16 Jun-16 Jul-16 Aug-16 Sep-16 Oct-16 Nov-16 Dec-16 Jan-17 Feb-17 Mar-17 Apr-17 May-17 Coleman R, et al. for GOG

GOG3005: PARPi Primary Therapy & Maint Recent Updates: • Change in global study chair from Kathy Bell-McGuinn to Robert Coleman • Clarification of dose and schedule modification for management of hematologic toxicity • Adjustment of starting dose for maintenance veliparib/placebo from 400 mg BID to 300 mg BID for 2 weeks, with option for escalation as tolerated • Following IDMC review, gBRCA status has been incorporated as a stratification factor (pre-randomization) and other stratifications have been simplified (to avoid over-stratification) Coleman R, et al. for GOG

GOG 0213: Recurrent Disease • Epithelial Ovarian, Fallopian, or Peritoneal Cancer • One prior therapy, Platinum-free interval > 6 months • Primary Endpoint: OS • Surgical accrual expanded to 485 patients to accertate analysis (2019) Carboplatin AUC=5 Maximal x 6-8 A Paclitaxel 175 mg/m 2 I Secondary Cytoreduction (No further therapy) R1 No Secondary R2 II Surgery Carboplatin AUC=5 B x 6-8 Paclitaxel 175 mg/m 2 Bevacizumab 15 mg/kg Not Surgical III Bevacizumab 15 mg/kg Candidate (Until progression) Open: 06-Dec-07 Closed: Ongoing (surgical) Target Accrual: 785 pts (485 surgical) Coleman RL, et al. SGO 2015

NRG-GY004: Platinum-Sensitive • Recurrent HGSC with PFI >6 months (following most recent platinum) • No more than 3 prior treatment regimens (including primary therapy) • RECIST measurable or evaluable disease with accessible tumor • No prior PARPi therapy, prior bevacizumab permitted • Stratify for BRCA status, number of prior treatment regimens • Primary endpoint: PFS 85% Power with HR 0.625 Olaparib 300 mg BID Cediranib 30 mg QD R Olaparib 200 mg BID Platinum-based combo* (IV) *Carboplatin + gemcitabine or paclitaxel or PLD Open: FEB 2106 Closed: (ongoing) n=130 as of 14OCT2016 Target Accrual: 450 pts (135 BRCA1/2 +) Liu J, for GOG

NRG-GY005: Platinum-Resistant • Recurrent HGSC with PFI <6 months (following most recent platinum) • No more than 2 prior treatment regimens (including primary therapy) • RECIST measurable or evaluable disease, biopsy accessible • No prior PARPi therapy, prior bevacizumab permitted • Stratify for BRCA status, number of prior treatment regimens • Primary endpoint: OS 90% Power with HR 0.625 Randomized Phase II (n = 180) Randomized Phase III (n = 280) Cediranib (PO) Selected Regimen (PO) Olaparib (PO) 1:1 R R Non-Platinum Chemo* (IV) Cediranib + Olaparib (PO) * Weekly paclitaxel or PLD Non-Platinum Chemo* (IV) Open: FEB 2106 Closed: (ongoing) n=53 as of 14OCT2016 Target Accrual: 460 pts (135 BRCA1/2 +) Lee J-M, for GOG

NRG-GY007: NACT +/- Ruxolitinib • Epithelial ovarian, peritoneal, or fallopian carcinoma (EOPFC) • Stage IIIC-IV and suitable for NACT with interval cytoreductive surgery • Phase I to evaluate acute toxicity (C1) and cumulative tolerability • Maintenance ruxolitinib permitted in patients tolerating concurrent therapy • Primary Endpoints: PFS and molecular targeting (stem cells and IL6) CP (x3) ICS CP (x3) Observation 1:2 Core Bx R CP (x3) CP (x3) Rux Maint ICS + Rux + Rux (optional) CP = Carboplatin AUC 5 or 6 (D1), Paclitaxel 80 mg/m2 (D1,8,15) Rux = Ruxolitinib 10-15 mg PO BID (pending Phase 1) ICS = Interval Cytoreductive Surgery Open: 10-OCT-2016 Closed: (ongoing phase I) Accrual: Burger R, for NRG Oncology

OVM1509: NACT +/- Pembrolizumab Gaillard S, for NRG (pending GCSC review)

OVM1629: NACT +/- Metformin Serum Yamada D, for NRG and U Chicago Ovarian SPORE (pending CTEP review)