Overview of Revised CTEP Schema for Cooperative Group Treatment Studies

1. Overview of Revised CTEP Schema for Review of Cooperative Group Treatment Studies OEWG Kick-Off Meeting Meg Mooney, MD Chief, Clinical Investigations Branch CTEP, DCTD, NCI – March 24, 2010

2. Review Process for Group Tx Trial Proposals All Cooperative Group study proposals will be initially evaluated as LOIs(Letters of Intent) OR Concepts, independent of entity holding the IND or if study IND-exempt, and undergo full scientific review (“developmental strategy” is no longer a review category) LOIs (CTEP Protocol Review Committee) Studies in Response to CTEP Mass Solicitation Phase 1 and Phase 1/2 Studies Phase 2 (and 1/2) Studies <100 Patients Transition Period: All Phase 2 Studies in diseases without SCs Post-meeting update: Group Phase 2 (and 1/2) > 100 pts without SCs are now Concepts. Concepts (Steering Committee (SC) Evaluation) Phase 2 (and 1/2) Studies ≥100 Patients Phase 3 Studies - Exception for OPEN Internat’l Phase 3 Transition Period: Phase 3 Studies in diseases without SCs will be reviewed by CTEP Concept Review Committee

3. Phase 2 Trials Eligible for New Reimbursement Phase 2 Treatment Trials with: Total sample size up to 125 patients (eligible & ineligible) for a treatment arm – does not include patients screened as part of the trial for assignment to a treatment arm (to be determined by CTEP at LOI/Concept approval) Trials may have a simple dose finding cohort, but it must be primarily a phase 2 trial Phase 2 Tx Trials with larger sample sizes are eligible for annual nominations to receive “complexity” funds Phase 2/3 Tx Trials are eligible for annual nominations to receive “complexity” funds

4. Phase 2 Trials New Reimbursement Total Cost of $5,000: $2,000 paid by Group leading or endorsing a trial and the additional total cost of $3,000 paid to Group via CTSU (if non-endorsing and on CTSU menu, CTSU pays full $5,000 total cost to Group; rules for Group phase 2 trial going on CTSU menu remain unchanged) Screened patients receive $500 only if not assigned to a treatment arm (this is a current estimate only – might be less than $500) Ancillary payments for collection of biospecimens included in $5,000 total cost CCOPs paid in equivalent “treatment credits”

5. Timeline: Implementation Date: March 15th 2010 for newly submitted proposals If SC has >2 new studies on Agenda (and cannot accommodate a 3rd phase 2 Concept, study will go to CTEP for review) New process will be closely monitored Non-CTEP IND or IND-Exempt Phase 2 Studies: Will come in on CTEP LOI or Concept form per the schema/criteria Groups need to designate on LOI form the proposal is for non-CTEP IND study (and list investigational agent) or an IND-exempt study IB will be required for non-CTEP IND agents if agent is investigational IB and/or adequate information supplied in LOI or Concept for non-CTEP IND agents that are commercially available. Transition Period: Only for “Non-CTEP IND” LOIs or Concepts NOT going to a SC; CTEP will accept “protocol” as LOI or Concept until 5/1/2010 – but it will be reviewed as a study proposal (not as a protocol) Implementation of Revised Review Process

7. OEWG Target Timeline Phase 2 Trial – 210 days All Timelines in Calendar Days Timeline pauses if industry negotiations cause delay Post-meeting note: Phase 1/2 or 2 Concepts of > 100 patients have a target timeline of 240 days (210 days + 30 days added to Concept approval stage = 240 days). LOI review LOI revision/ review Protocol development Protocol review Protocol revision/review and forms development 0 30 60 120 150 210 Time (days) Timeline excludes contracting, drug supply, IRB, FDA (Subsequently changed during implementation in that IRB is no longer considered a time-out. Please see Time-Out SOP.) Protocol terminated if not activated in 18 months “Activation” for Target and Final (“Drop-Dead”) Timelines is defined as trial being OPEN for patient enrollment

9. Phase 1/Phase 2 Timeline: Unsolicited LOIs – Non-CTEP IND or No IND Phase 1 and Phase 2 <100 Patients Post-meeting update: For the most updated OEWG timelines, please see the Timeline Charts on the OEWG website at http://ctep.cancer.gov/SpotlightOn/OEWG.htm

10. Transition Period:Pediatric, Brain/CNS, & Melanoma Studies will not have SCs until end CY 2010, large Phase 2 and Phase 3 proposals will be evaluated by CTEP Concept or Protocol Review Committee until SCs up and running

11. Concept Review & Protocol Development Process in Detail with Timelines OEWG Kick-Off Meeting Meg Mooney, MD Chief, Clinical Investigations Branch CTEP, DCTD, NCI – March 24, 2010

12. OEWG Target Timeline Phase 3 Trial – 300 days All Timelines in Calendar Days Timeline pauses if industry negotiations cause delay Feedback on major challenges If registration trial, FDA review in 21 (to 30) days Concept review Concept revision/ review cycles Protocol development Protocol review Protocol revision/review cycles Forms development 0 30 90 300 180 210 Time (days) Timeline excludes IRB, contracting, drug supply (Subsequently changed during implementation in that IRB is no longer considered a time-out. Please see Time-Out SOP.) Protocol terminated if not activated in two years “Activation” for Target and Final (“Drop-Dead”) Timelines is defined as trial being OPEN for patient enrollment

13. Group Phase 3 Timeline – Steering Committee Evaluation Post-meeting update: For the most updated OEWG timelines, please see the Timeline Charts on the OEWG website at http://ctep.cancer.gov/SpotlightOn/OEWG.htm

14. Group Phase 2 Timeline – Steering Committee Evaluation Post-meeting update: For the most updated OEWG timelines, please see the Timeline Charts on the OEWG website at http://ctep.cancer.gov/SpotlightOn/OEWG.htm