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George S , Chi P , Heinrich MC , von Mehren M , Jones RL , Ganjoo K , Trent J , Gelderblom H , Razak AA , Gordon MS , Somaiah N , Jennings J , Meade J , Shi K , Su Y , Ruiz-Soto R , Janku F
Ripretinib intrapatient dose escalation after disease progression provides clinically meaningful outcomes in advanced gastrointestinal stromal tumour
Eur J Cancer. 2021 Aug 11;155 :236-244
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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.
1879-0852 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 Journal Article England Eur J Cancer. 2021 Aug 11;155:236-244. doi: 10.1016/j.ejca.2021.07.010.