SARC015: Phase II study of R1507 in wild-type GIST - PowerPoint PPT Presentation

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SARC015: Phase II study of R1507 in wild-type GIST

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SARC015: Phase II study of R1507 in wild-type GIST

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  1. SARC015: Phase II study of R1507 in wild-type GIST Margaret von Mehren, Fox Chase Cancer Center Katie Janeway, Dana Farber Cancer Institute

  2. 10% of GISTs in adults and 85% of GISTs in pediatric patients are wild-type (WT) TKIs in WT GIST TKIs in pediatric GIST No objective responses to imatinib 1 PR to sunitinib Background Heinrich et al., JCO 2008 (epub)

  3. Background: IGF1R in GIST

  4. Background: IGF1R in GIST • IGF1R expression in pediatric WT GIST 10x that in adult WT GIST* KIT mutant Pediatric wild-type IGF1R Actin *Agaram. Clin Cancer Res, 2008

  5. Background: R1507 • Pediatric phase I • At 9mg/kg weekly dose similar pharmacokinetics and exposure • No DLTs yet reported • Similar AEs

  6. Schema Adult and Pediatric cohorts Pediatric: Age at diagnosis ≤ 18 years Adult: Age at diagnosis > 18 years Baseline tumor assessment: CT or MRI of all disease sites PET (optional) as clinically indicated R1507 IV 9 mg/kg weekly Evaluate by CT/MRI: q 9 weeks x 27 weeks then q 12 weeks • Off treatment criteria: • intercurrent illness that prevents treatment • unacceptable adverse events • patient withdraws • unacceptable for further treatment in the judgment of investigator SD or Response PD Continue R1507 IV at 9 mg/kg weekly Off treatment Off treatment evaluations

  7. Objectives • Primary: • Clinical benefit rate (SD>6 mos., PR or CR) in patients with advanced WT GIST treated with R1507 • Secondary: • Response duration, TTP and PFS • Tolerability and adverse event profile • Exploratory • Serum and tumor biomarkers • BMI, glucose, lipid metabolism and linear growth (pediatric only) • PET scans when obtained for clinical care

  8. Eligibility • Advanced, unresectable GIST • KIT and PDGFRA mutation analysis: WT • Age > 2 years • Performance status • Adequate organ function • Diabetic patients must have good glucose control • No prior therapy targeting IGF1R • Off TKI therapy x 7 days • Co-existence of paraganglioma and pulmonary chondroma is permitted

  9. Overview • Cohorts • Pediatric: Age at diagnosis≤18. • Adult: Age at diagnosis>18. • R1507 administration • 9 mg/kg IV weekly • Duration: Until progression, intercurrent illness, unacceptable adverse event, delays • Concurrent therapy • No TKI therapy • If response, surgery permitted after 6 months

  10. Overview • Response evaluation • CT/MRI q 9 weeks x 27 weeks then q 12 weeks • WHO criteria for the primary outcome • CHOI criteria as a secondary objective • Biological correlates • Blood, paraffin embedded specimens, and when possible, fresh frozen tumor to be obtained

  11. Adverse event monitoring • Chemistries, glucose, liver function tests, blood counts weekly • HbA1c start of study, off study • Human anti-human antibodies (HAHA) weeks 1, 4, 12, 18

  12. Timeline • Protocol completed • November 15, 2008 • Statistical input • SARC review • Submit to Roche for review • Goal open date: February 1, 2009