Ripretinib intrapatient dose escalation after disease progression provides clinically meaningful outcomes in advanced gastrointestinal stromal tumour. Academic Article uri icon

Overview

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.

authors

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

publication date

  • August 12, 2021

Research

keywords

  • Gastrointestinal Stromal Tumors
  • Naphthyridines
  • Protein Kinase Inhibitors
  • Urea

Identity

PubMed Central ID

  • PMC9362852

Scopus Document Identifier

  • 85112367472

Digital Object Identifier (DOI)

  • 10.1016/j.ejca.2021.07.010

PubMed ID

  • 34391056

Additional Document Info

volume

  • 155