July 12, 2014

NRG Oncology Research Strategy Committee Update

Mitchell Machtay, M.D.Deputy Group Chair for Research Strategy

July 12, 2014

NRG StructureRSC and CPAC Report to Group Chairs

NRG Research StrategyCommittee (RSC)

• NRG Internal Peer review of Protocol concepts submitted by NRG committees – ~50 members.

• Meets face-to-face at semi-annual meetings.– Periodic teleconferences between meetings.

• Voting and scoring performed by the RSC members via survey-monkey post-meeting.

• Protocol concepts with a ‘positive’ vote are sent to NRG CPAC for prioritization

Voting/Prioritizing Scientific Merit Score

Score Adjectival Descriptor

1 Outstanding (top 20%, worth finding resources)

2 Excellent (worth conducting if resources available)

3 Good (conduct only if excess resources available)

4 Poor (near fatal flaw, conduct only if desperate)

5 Do not consider further (even if desperate)

Feasibility ScoreScore Adjectival Descriptor1 Fully feasible (answers study questions, patients available)

2 Partially feasible (only one of above two criteria present)

3 Not feasible (neither of two criteria present)

RSC Concepts ApprovedBy NRG Thus Far

• Legacy protocols already well under development by NSABP, RTOG, GOG.

• Series of ‘Nivo’ protocol concepts in response to high priority NCI mass solicitation.– Brain, H&N, Lung, Cervix, Ovary

• Nine protocol concepts formally reviewed and presented at February 2014 NRG meeting:– 2 brain; 4 GYN; 2 Lung; 1 Sarcoma

• Brain/CNS: 2• Breast: 2• Gastrointestinal: 1• Genitourinary: 2• Gyn (incl. Dev. Ther.): 3• Head & Neck: 1• Lung/Thoracic: 1• CPC: 1

OEWG Developing Studies(Concepts NCI Approved)

Developing Concepts(Concepts NRG RSC Approved

But not yet NCI approved)

• Brain/CNS: 3• Breast: 1• Gastrointestinal: 0• Genitourinary: 0• Gyn (incl. Dev. Ther.): 9• Head & Neck: 0• Lung/Thoracic: 1• CPC: 1

OEWG Developing Studies(i.e. NCI approved concepts)

• Breast: N=2– BR-001: Multifocal SBRT for oligometastatic disease (Ph. I)– BR-002: Unifocal SBRT for oligometastatic disease (Ph. II/III)

• Gynecologic: N=3– GY-001: XL-184 for recurrent ovarian CA (Ph. II)– GY-00x: Nivolumab for recurrent cervix CA (Ph. II)– GY-00x: Nivolumab/Ipilimumab for adv. ovarian CA (Ph. II)

• Cancer Control/Prevention: N=1– CC-001: Memantine/hippocampal sparing brain RT for

metastases (Ph. III)

OEWG Developing Studies(i.e. NCI approved concepts)

• Brain/CNS: N=2– BN-001: High dose IMRT/protons for GBM (Ph. III)– BN-002: RT/Temodar/Nivolumab for GBM (Ph. I)

• Head and Neck: N=2– HN-001: EBV-based chemo-RT for Nasoph CA (Ph II/III).– HN-002: RT/chemo dose for HPV+ Oroph. (Ph II)

• Gastrointestinal: N=1– GI-001: Chemo +/- RT for CholangioCA (Ph. III)

• Lung: N=1– LU-001: Chemo-RT +/- Metformin for Lung CA (Ph. II)

• Genitourinary: N=1– GU-001: Postop IMRT for Loc. Adv. bladder CA (Ph. II/III)

NRG Developing Concepts(i.e. RSC approved but not NCI approved)

• Brain: N=3– RT + Veliparib (ABT-888) for GBM (Ph. IIR)– RT/Temodar + Valcyte for GBM (Ph. IIR)– Postop RT for Atypical Meningioma (Ph. IIR)

• Breast: N=1– Advanced Imaging/biopsies after Neoadjuvant Tx. (Ph. II)

• Lung: N=2– Local RT/SBRT for oligometastatic Stage IV NSCLC (Ph. IIR)– Pazopanib after SBRT for oligometastatic sarcoma (Ph. IIR)

• Cancer Control/Prevention: N=1– Hippocampal sparing prophylactic cranial irradiation for small

cell lung CA.

NRG Developing Concepts(i.e. RSC approved but not NCI approved)

• GYN (incl. Dev. Ther.): N= 9– Paclitaxel +/- Nintedanib (BIBF1120) for Adv. Endometrium.– Chemo-RT +/- Triapine for Loc. Adv. Cervix CA.– Chemo vs. Trametinib for L.G. Serous Ovary CA– Trametinib + GSK214179 (akt-i) for L.G. Serous Ovary CA– IMGN 853 + carbo vs. chemo for Ovarian CA– Carbo/Paclitaxel +/- OMF-54F28 for Uterine sarcoma– Cediranib/Olaparib vs. chemo for rec. Ovary (Pt sensitive).– Cediranib vs. Olaparib vs. both for rec. Ovary (Pt resistant)– Lymphadenectomy vs. no Lymphadenecotomy Endometrial CA

Summary• NRG ‘Pipeline’ includes:

– 13 studies ‘approved’ by NCI, on OEWG timeline.– 15 studies ‘approved’ by NRG-RSC, being submitted

or resubmitted to NCI.

• Heavily weighted toward GYN cancer (including Dev. Therapeutics).

• Heavily weighted toward early phase trials.• Consistent with NCI goals for the new NCTN to

have fewer trials, less accrual than previously.

The King (of Protocols)is Back!