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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
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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
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Study Schema N=40 Linsitinib (150 mg PO BID on days 1-28, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity) Pediatric WT Eligibility Criteria: Diagnosis ≤18 years of age or diagnosis of Carney Triad or Carney- Stratakis DyadDiagnosis ≤18 years of age or diagnosis of Carney Triad or Carney- Stratakis Dyad Progressed on or intolerant to at least sunitinibProgressed on or intolerant to at least sunitinib Adult WT Eligibility Criteria: Diagnosis >18 years of age and no diagnosis of Carney Triad or Carney- Stratakis DyadDiagnosis >18 years of age and no diagnosis of Carney Triad or Carney- Stratakis Dyad Progressed on or intolerant to at least imatinibProgressed 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
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Patient Demographics, n=20 Gender Female Male 12 8 Age18-62, average 41 Pediatric type Carney Triad 6262 Performance Status 0/1/212/7/1 Primary Site Stomach (Gastroesophageal) Small bowel Peritoneum 16 (1) 2 1 Metastatic Sites Liver Peritoneum Lymph Nodes 17 11 4 Prior Therapies Imatinib Sunitinib Sorafenib 1-7, median 3 19 7
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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
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Primary Objective: ORR by RECIST 1.1 Data as of 9/30/13 % Change in Tumor Volume
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Metabolic Responder Baseline Week-8 Follow-up
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Metabolic Progressor Baseline Week 8 Follow-up
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Clinical Benefit Rate 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
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Time on Study based on Gender Days on Study Lighter color bars are patients off study Female Male
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Time on Study by Primary Site Time on Study in Days Black boxed patients are off study
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PFS and OS 6-Month PFS Estimate: 70% Events/N: 6/20 6-Month OS Estimate: 85% Events/N: 3/20
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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
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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
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