1. Dinutuximab (ch14.18) for children with high-risk neuroblastoma
Malcolm A. Smith, MD, PhD
Cancer Therapy Evaluation Program
National Cancer Institute
November 3, 2015

2. Neuroblastoma Most common extra-cranial solid tumor in children
700 cases per year in U.S.
90% are younger than 5 years at diagnosis, with a median age at diagnosis of 19 months
Approximately 50% have “high risk” features
Overall survival for high-risk neuroblastoma < 50%

3. Dinutuximab (ch14.18) for Children with High Risk Neuroblastoma
Over 99% of neuroblastoma expresses GD2 on cell surface
Normal tissue expression: tissues of neuroectodermal origin, e.g., skin and nervous system tissue
Dinutuximab (ch14.18) binds GD2 and has potent ADCC and CDC activity
Matthay & George, Clin Cancer Res. 2012: 8(10):

4. Dinutuximab (ch14.18) for Children with High Risk Neuroblastoma
Over 99% of neuroblastoma expresses GD2 on cell surface
Normal tissue expression: tissues of neuroectodermal origin, e.g., skin and brain tissue
Dinutuximab (ch14.18) binds GD2 and has potent ADCC and CDC activity
Matthay & George, Clin Cancer Res. 2012: 8(10):
Matthay & George, Clin Cancer Res. 2012: 8(10):

5. Dinutuximab (ch14.18) for Children with High Risk Neuroblastoma
Over 99% of neuroblastoma expresses GD2 on cell surface
Normal tissue expression: tissues of neuroectodermal origin, e.g., skin and brain tissue
Dinutuximab (ch14.18) binds GD2 and has potent ADCC and CDC activity
Matthay & George, Clin Cancer Res. 2012: 8(10):

6. Dinutuximab (ch14.18) for Children with High Risk Neuroblastoma
1990’s: Phase 1-2 clinical trials
1998: Request to NCI to manufacture agent for phase 3 trial
2001: ANBL0032 activated
2009: Positive results for ANBL0032 identified
2009: ANBL0032 continues as single arm study
2009: ANBL0931 activated
2010: United Therapeutics announced as NCI CRADA partner
Children’s Oncology Group

7. Dinutuximab (ch14.18) for Children with High Risk Neuroblastoma
1990’s: Phase 1-2 clinical trials
1998: Request to NCI to manufacture agent for phase 3 trial
2001: ANBL0032 activated
2009: Positive results for ANBL0032 identified
2009: ANBL0032 continues as single arm study
2009: ANBL0931 activated
2010: United Therapeutics announced as NCI CRADA partner

8. Dinutuximab (ch14.18) for Children with High Risk Neuroblastoma
1990’s: Phase 1-2 clinical trials
1998: Request to NCI to manufacture agent for phase 3 trial
2001: ANBL0032 activated
2009: Positive results for ANBL0032 identified
2009: ANBL0032 continues as single arm study
2009: ANBL0931 activated
2010: United Therapeutics announced as NCI CRADA partner

9. Dinutuximab (ch14.18) for Children with High Risk Neuroblastoma
1990’s: Phase 1-2 clinical trials
1998: Request to NCI to manufacture agent for phase 3 trial
2001: ANBL0032 activated
2009: Positive results for ANBL0032 identified
2009: ANBL0032 continues as single arm study
2009: ANBL0931 activated
2010: United Therapeutics announced as NCI CRADA partner
ANBL0032 EFS Results (2009)
Yu, et al. N Engl J Med. 2010;363:

10. Dinutuximab (ch14.18) for Children with High Risk Neuroblastoma
1990’s: Phase 1-2 clinical trials
1998: Request to NCI to manufacture agent for phase 3 trial
2001: ANBL0032 activated
2009: Positive results for ANBL0032 identified
2009: ANBL0032 continues as single arm study
2009: ANBL0931 activated
2010: United Therapeutics announced as NCI CRADA partner
March 2015

11. Public-Private Partnership to Successfully Develop a New Treatment for Children with High-Risk Neuroblastoma
NCI
UTC
COG

12. Public-Private Partnership to Successfully Develop New Treatments for Children with High-Risk Cancers
NCI
UTC
COG
NCI manufacturing (if necessary) of anticancer agent
NCI preclinical in vivo testing of clinical candidate
Clinical trials through NCI-supported consortia (e.g., COG Phase 1 Consortium) and NCI National Clinical Trials Network
Collaboration with pharmaceutical company for commercialization
Incentives from Creating Hope Act