1 / 15

M von Mehren, M Heinrich, S Schuetze, K Ganjoo, J Yu, J Yap, AD Van den Abbeele,

Interim Analysis of SARC022, A Phase II study of Linsitinib in Pediatric and Adult Wild Type (WT) Gastrointestinal Stromal Tumors (GIST). M von Mehren, M Heinrich, S Schuetze, K Ganjoo, J Yu, J Yap, AD Van den Abbeele, J Wright, S George. Background.

amber
Download Presentation

M von Mehren, M Heinrich, S Schuetze, K Ganjoo, J Yu, J Yap, AD Van den Abbeele,

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. Interim Analysis of SARC022, A Phase II study of Linsitinib in Pediatric and Adult Wild Type (WT) Gastrointestinal Stromal Tumors (GIST) M von Mehren, M Heinrich, S Schuetze, K Ganjoo, J Yu, J Yap, AD Van den Abbeele, J Wright, S George

  2. Background • WT GIST in adults and children are less responsive to tyrosine kinase inhibitors compared to GIST tumors with KIT/PDGFRA mutations • Insulin-like growth factor-1 receptor (IGF-1R), a member of the insulin receptor family (IR), has been demonstrated to be highly expressed on WT GIST • We hypothesized that growth and proliferation in these tumors may be IGF-1R-dependent, and therefore, linsitinib, a dual inhibitor of IGF-1R and IR, might demonstrate clinical benefit in this patient population

  3. Study Schema • Pediatric WT Eligibility Criteria: • Diagnosis ≤18 years of age or diagnosis of Carney Triad or Carney-StratakisDyad • Progressed on or intolerant to at least sunitinib Linsitinib (150 mg PO BID on days 1-28, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity) N=40 • Adult WT Eligibility Criteria: • Diagnosis >18 years of age and no diagnosis of Carney Triad or Carney-StratakisDyad • Progressed on or intolerant to at least imatinib Primary end point: ORR Secondary end points: SD ≥9 months, PFS, OS, time to progression, metablic responses http://clinicaltrials.gov/ct2/show/NCT01560260

  4. Patient Demographics, n=20

  5. Toxicities • Hyperglycemia: • One grade 2 episode in a patient on steroids for Iodine IV contrast allergy prophylaxis • No increases in HgbA1c levels • No evidence of drug induced: • Hepatotoxicity • QTc prolongation

  6. Primary Objective:ORR by RECIST 1.1 % Change in Tumor Volume Data as of 9/30/13

  7. Metabolic Responder Baseline Week-8 Follow-up

  8. Metabolic Progressor Baseline Week 8 Follow-up

  9. Clinical Benefit Rate (CR, PR and SD > 9 months) • As of last data cut off of 9/30/13: • 15% (3/20 patients) have remained on study for greater than 9 months • 55% (11/20 patients) have had stable disease for at least 6 months, with 10 remaining on study • 1 additional patients remains on study for greater than 4 months

  10. Time on Study based on Gender Female Male Days on Study Lighter color bars are patients off study

  11. Time on Study by Primary Site Time on Study in Days Black boxed patients are off study

  12. PFS and OS 6-Month OS Estimate: 85% Events/N: 3/20 6-Month PFS Estimate: 70% Events/N: 6/20

  13. Conclusions • Clinical trials in WT GIST are feasible • Linsitinib is well tolerated without any unanticipated toxicities • We have not seen Recist 1.1 ORR to date • 55% of patients have had stable disease for six months or longer • Of the patients reviewed, 15% have had EORTC metabolic response by FDG-PET • Additional correlative studies are being completed

  14. Acknowledgements The Patients and their families Correlative Science:Funding: Martin Belinsky NCI R21 CA150381 Katherine Janeway NCI R01 CA106588 FCCC Molecular Diagnostics SARC Laboratory SARC Clinical Trials Office: Ann Johnson, Brenda Steltzriede, Denise Reinke CRAB.org: John Crowley, Antje Hoering CTEP: John Wright, MD, PhD

More Related