Dr. Zalcberg on the Rationale for Dose Escalation With Ripretinib in Advanced GIST

John Raymond Zalcberg, PhD, MBBS, a professor of Cancer Research in the School of Public Health and Preventative Medicine at Monash University, discusses the rationale for intra-patient dose escalation with ripretinib (Qinlock), as was examined in the phase 3 INVICTUS trial (NCT03353753) in patients with advanced gastrointestinal stromal tumors (GIST).

In the phase 1 dose-escalation portion of the research, the maximum tolerated dose of ripretinib had not yet been reached, according to Zalcberg, even when given at a daily dose of 400 mg or a twice-daily dose of 200 mg. As such, there was a rationale to increase the dose from a toxicity standpoint the phase 3 trial, Zalcberg notes. However, it was unknown whether the efficacy would be sustained, Zalcberg adds. 

Although TKIs with a variety of targets are sometimes used for patients with GIST who progress on ripretinib, limited approved, active options are available, Zalcberg says. INVICTUS provided patients with an opportunity to benefit from ripretinib, Zalcberg adds. In the clinic, some patients progressed on the daily dose of 150 mg and continued to derive benefit with dose escalation, Zalcberg concludes.