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)

• 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

GOG212: Ovarian Maintenance

x 12 I PG-Paclitaxel 175 mg/m2 (15 m), q28d x 12 II Paclitaxel 175 mg/m2 (3 h), q28d III Observation Open: 21-MAR-2005 Closed: 13-JAN-2014 (9 y) Target Accrual: Target 1100 pts (actual 1157) Copeland L, for NRG (pending) Primary Rx: Carboplatin and Taxane (5-6 Cy)

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

• ther 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…”

• Epithelial Ovarian, Fallopian, or Primary Peritoneal Cancer
• Optimal and Suboptimal Disease (through April 2011)
• Primary Endpoint: PFS (Analysis JAN 2016)

GOG0252: IP Therapy

Open: 27-Jun-2009 Closed: 29-Oct-2011 Accrual: 1560 pts (max 250 suboptimal) Walker J. for GOG, SGO 2016 Carboplatin AUC=6 (IV) Paclitaxel 80 mg/m2 IV (d1,8,15) Bevacizumab (C2-6) Cisplatin 75 mg/m2 (IP) Paclitaxel 135 mg/m2 (d1, 3h) Paclitaxel 60 mg/m2 (d8, IP) Bevacizumab (C2-6) I III II Carboplatin AUC=6 (IP) Paclitaxel 80 mg/m2 (d1,8,15) Bevacizumab (C2-6) Bevacizumab q21d x 16 Bevacizumab q21d x 16 Bevacizumab q21d x 16

IV Carbo IP Carbo IP Cisplatin

0.0 0.2 0.4 0.6 0.8 1.0 12 24 36 48 60 72 Progression-Free Survival Months on Study

GOG0252: IP vs IV (PFS)

Walker J. et al, SGO LBA 2016

Regimen Events Median Carboplatin (IV) + Paclitaxel (IV) 303/461 26.8 Carboplatin (IP) + Paclitaxel (IV) 300/464 28.7 Cisplatin (IP) + Paclitaxel (IV+IP) 307/456 27.8

Optimal Cytoreduction (Stage II-III)

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

GOG0252: IP vs IV (PFS)

Walker J. for GOG, 2016

ITT (All Eligible Patients)

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

x 6 II Veliparib 400 mg PO BID Paclitaxel (standard or dose-dense) Carboplatin AUC 6 (IV)* Veliparib 150 mg PO BID x 6 I Paclitaxel (standard or dose-dense) Carboplatin AUC 6 (IV)* Placebo PO BID Placebo PO BID Collaborative development with AbbVie (M13-694) including international participation, seeking EMA and FDA regulatory approval

Coleman R, et al. for GOG Open: JUL 2015 Closed: (ongoing) Target Accrual: ~1100 pts (264 BRCA1/2 +)

x 6 II Placebo PO BID Paclitaxel (standard or dose-dense) Carboplatin AUC 6 (IV)* Veliparib 150 mg PO BID

1:1:1

GOG3005: PARPi Primary Therapy & Maint

Coleman R, et al. for GOG 250 500 750 1000 1250 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

Projected Subjects Cumulative (Balanced) Actual Subjects Cumulative (Balanced) Projected Subjects Cumulative (Aggressive)

645 Currently accruing several months ahead of original projection

GOG3005: PARPi Primary Therapy & Maint

Coleman R, et al. for GOG

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)

Maximal Secondary Cytoreduction No Secondary Surgery

• 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)

Open: 06-Dec-07 Closed: Ongoing (surgical) Target Accrual: 785 pts (485 surgical) I II

GOG 0213: Recurrent Disease

Coleman RL, et al. SGO 2015 Carboplatin AUC=5 Paclitaxel 175 mg/m2 (No further therapy) Carboplatin AUC=5 Paclitaxel 175 mg/m2 Bevacizumab 15 mg/kg Bevacizumab 15 mg/kg (Until progression) A B R1 Not Surgical Candidate III x 6-8 x 6-8 R2

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

Cediranib 30 mg QD Olaparib 200 mg BID Platinum-based combo* (IV) R *Carboplatin + gemcitabine or paclitaxel or PLD Olaparib 300 mg BID 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

Open: FEB 2106 Closed: (ongoing) n=53 as of 14OCT2016 Target Accrual: 460 pts (135 BRCA1/2 +) Lee J-M, for GOG Cediranib (PO) Olaparib (PO) Cediranib + Olaparib (PO) R Randomized Phase II (n = 180) Selected Regimen (PO) Non-Platinum Chemo* (IV) R Randomized Phase III (n = 280) * Weekly paclitaxel or PLD 1:1 Non-Platinum Chemo* (IV)

• 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 CP (x3) + Rux CP (x3) + Rux Rux Maint (optional) ICS Core Bx

R

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

1:2

Burger R, for NRG Oncology

NRG-GY007: NACT +/- Ruxolitinib

Open: 10-OCT-2016 Closed: (ongoing phase I) Accrual:

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)