1 / 12

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

SARC015: Phase II study of R1507 in wild-type GIST. Margaret von Mehren, Fox Chase Cancer Center Katie Janeway, Dana Farber Cancer Institute. 10% of GISTs in adults and 85% of GISTs in pediatric patients are wild-type (WT) TKIs in WT GIST TKIs in pediatric GIST

more
Download Presentation

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

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  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

More Related