Linsitinib (OSI-906) for the treatment of adult and pediatric wild-type gastrointestinal stromal tumors, a SARC phase II study

Margaret Von Mehren, Suzanne George, Michael C. Heinrich, Scott M. Schuetze, Jeffrey T. Yap, Jain Q. Yu, Amanda Abbott, Samuel Litwin, John Crowley, Martin Belinsky, Katherine A. Janeway, Jason L. Hornick, Douglas B. Flieder, Rashmi Chugh, Lori Rink, Annick D. Van Den Abbeele

    Research output: Contribution to journalArticle

    2 Scopus citations

    Abstract

    Purpose: Most gastrointestinal stromal tumors (GIST) have activating mutations of KIT, PDGFRA, or uncommonly BRAF. Fifteen percent of adult and 85% of pediatric GISTs are wild type (WT), commonly having high expression of IGF-1R and loss of succinate dehydrogenase (SDH) complex function. We tested the efficacy of linsitinib, an oral TKI IGF-1R inhibitor, in patients with WT GIST. Patients and Methods: A multicenter phase II trial of linsitinib was conducted. The primary endpoint was objective response rate. Secondary endpoints were clinical benefit rate: complete response, partial response, and stable disease (SD) ≥ 9 months, and quantitative 2[18F]fluoro-2-deoxy-D-glucose (FDG) metabolic response (MR) at week 8. Serum levels for glucose, insulin, IGF-1R ligand IGF1, and binding proteins were obtained to explore correlations to patient outcomes and FDG-PET results. Results: Twenty patients were accrued in a 6-month period. Grade 3-4 toxicities possibly related to linsitinib were uncommon (8.5%). No objective responses were seen. Clinical benefit rate (CBR) at 9 months was 40%. Intense FDG uptake was observed at baseline, with partial MR of 12% and stable metabolic disease of 65% at week 8; these patients had RECIST 1.1 SD as their best response. Progression-free survival (PFS) and overall survival Kaplan-Meier estimates at 9 months were 52% and 80%, respectively. SDHA/B loss determined by IHC was seen in 35% and 88% of cases, respectively. Conclusions: Linsitinib is well tolerated in patients with WT GIST. Although the 9-month CBR was 40%, and PFS at 9 months was 52%, no objective responses were observed. Rapid accrual to this study demonstrates that clinical trials of experimental agents in selected subtypes of GIST are feasible.

    Original languageEnglish (US)
    Pages (from-to)1837-1845
    Number of pages9
    JournalClinical Cancer Research
    Volume26
    Issue number8
    DOIs
    StatePublished - Apr 15 2020

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

    Fingerprint Dive into the research topics of 'Linsitinib (OSI-906) for the treatment of adult and pediatric wild-type gastrointestinal stromal tumors, a SARC phase II study'. Together they form a unique fingerprint.

  • Cite this

    Von Mehren, M., George, S., Heinrich, M. C., Schuetze, S. M., Yap, J. T., Yu, J. Q., Abbott, A., Litwin, S., Crowley, J., Belinsky, M., Janeway, K. A., Hornick, J. L., Flieder, D. B., Chugh, R., Rink, L., & Van Den Abbeele, A. D. (2020). Linsitinib (OSI-906) for the treatment of adult and pediatric wild-type gastrointestinal stromal tumors, a SARC phase II study. Clinical Cancer Research, 26(8), 1837-1845. https://doi.org/10.1158/1078-0432.CCR-19-1069