Dinutuximab (ch14.18) for children with high-risk neuroblastoma Malcolm A. Smith, MD, PhD Cancer...

Dinutuximab (ch14.18) for children with high-risk neuroblastoma

Malcolm A. Smith, MD, PhD

Cancer Therapy Evaluation Program

National Cancer Institute

November 3, 2015

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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%

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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

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Normal tissue expression: tissues of neuroectodermal origin, e.g., skin and brain tissue


Matthay & George, Clin Cancer Res. 2012: 8(10):2740-53

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Normal tissue expression: tissues of neuroectodermal origin, e.g., skin and brain tissue


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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


2010: United Therapeutics announced as NCI CRADA partner

Children’s Oncology Group

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p=0.0115

0.00

0.20

0.40

0.60

0.80

1.00

Pro

babi

lity

(%)

113 69 47 29 15 9 3t rt 2113 59 32 20 10 8 1t rt 1

risk (n)

0 1 2 3 4 5 6

time (years)

RA only, trt 1

RA + anti-GD2, trt 2

COG-ANBL0032, - EFS randomized patients treatment 1 (n=113) & treatment 2 (n=113)

Yu, et al. N Engl J Med. 2010;363:1324-34

ANBL0032 EFS Results (2009)

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March 2015

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Public-Private Partnership to Successfully Develop a New Treatment for Children with High-Risk Neuroblastoma

NCI

UTC COG

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Public-Private Partnership to Successfully Develop New Treatments for Children with High-Risk Cancers

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

NCI

UTC COG

www.cancer.gov www.cancer.gov/espanol

Dinutuximab (ch14.18) for children with high-risk neuroblastoma Malcolm A. Smith, MD, PhD Cancer...

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