Ripretinib intrapatient dose escalation after disease progression provides clinically meaningful outcomes in advanced gastrointestinal stromal tumour

Suzanne George, Ping Chi, Michael C. Heinrich, Margaret von Mehren, Robin L. Jones, Kristen Ganjoo, Jonathan Trent, Hans Gelderblom, Albiruni A. Razak, Michael S. Gordon, Neeta Somaiah, Julia Jennings, Julie Meade, Kelvin Shi, Ying Su, Rodrigo Ruiz-Soto, Filip Janku

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Purpose: Ripretinib is a switch-control tyrosine kinase inhibitor that broadly inhibits KIT and platelet-derived growth factor receptor α kinase signalling. Ripretinib showed preliminary efficacy in patients with advanced gastrointestinal stromal tumour (GIST) in a phase I study across a range of doses. Results were confirmed in the phase III INVICTUS study, and ripretinib 150 mg once daily (QD) was subsequently approved as a ≥fourth-line therapy. Here, we report the phase I study results of intrapatient dose escalation (IPDE) in patients with GIST treated across second, third and later lines of therapy. Methods: Patients with advanced GIST who experienced disease progression (PD) at ripretinib 150 mg QD could dose escalate to 150 mg twice daily (BID). Progression-free survival (PFS) 1 was calculated from the date of the first dose of ripretinib 150 mg QD to PD (as per Response Evaluation Criteria in Solid Tumours 1.1); PFS2 was from the date of IPDE (150 mg BID) to PD or death. Treatment-emergent adverse events (TEAEs) were summarised by dosing periods and compared descriptively. Results: Of 142 patients with GIST receiving ripretinib 150 mg QD, 67 underwent IPDE. IPDE provided benefit across all lines of therapy; the median PFS2 was 5.6, 3.3 and 4.6 months for patients on second-, third- and ≥fourth-line therapy, respectively. A partial metabolic response after IPDE was demonstrated in 13 of 37 patients with available positron emission tomography scans. TEAEs reported at both doses were similar. Conclusion: Ripretinib IPDE after PD provided continued clinical benefit in advanced GIST across second, third and later lines of therapy with a similar safety profile to that observed with the QD regimen.

    Original languageEnglish (US)
    Pages (from-to)236-244
    Number of pages9
    JournalEuropean Journal of Cancer
    Volume155
    DOIs
    StatePublished - Sep 2021

    Keywords

    • Disease progression
    • Gastrointestinal stromal tumours
    • Pharmacology
    • Progression-free survival
    • Ripretinib

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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