INVICTUS study results reveal intra-patient dose escalation (IPDE) of ripretinib after disease progression indicate clinical benefit and tolerability in patients with advanced gastrointestinal stromal tumor, presented at the 2021 ASCO Annual Meeting.

The INVICTUS study evaluated 129 randomized patients administered ripretinib, a switch-control tyrosine kinase inhibitor that broadly inhibits KIT and PDGFRA kinase signaling, (2:1) 150 mg once daily, with tumor response assesments performed every 28 days for 4 cycles (followed by everyday 56 days thereafter). To note, patients receiving ripretinib 150 mg QD who experienced progressive disease, as evaluated by means of blinded independent central review via mRECIST, were given the option for IPDE to 150 mg BID.

Moreover, the primary endpoint was PFS. For this investigative analysis, PFS1 for IPDE patients was defined as the time from randomization to PD; PFS2 for IPDE patients was the time from the first dose of ripretinib 150 mg BID to PD or death. PFS1 and PFS2 were based on BICR.

Among the 129 patients, 85 were treated with ripretinib 150 mg QD, and 43 patients with BICR PD dose escalated to 150 mg BID. Investigators reported baseline characteristics of IPDE patients, at time of study entry, were similar to those observed in the original ripretinib QD arm and similar to the 22 patients with BICR PD who either remained on 150 mg QD or discontinued treatment.

IPDE patients had a mPFS1 of 4.6 months and a mPFS2 of 3.7 months respectively. The IPDE dosing period was well tolerated without the emergence of new safety concerns. The most common treatment-emergent adverse events for patients included abdominal pain and anemia. IPDE from QD to BID resulted in an approximately 2-fold increase in the steady state trough concentration.

“Similar to the phase 1 study wherein IPDE to 150 mg BID following PD provided clinical benefit with a mPFS1 of 5.5 months and mPFS2 of 4.6 months (mPFS2/mPFS1=84%) for patients with ≥4th-line GIST, these analyses from INVICTUS indicate that IPDE to ripretinib 150 mg BID can also provide additional meaningful clinical benefit and a similar tolerability profile to the 150 mg QD regimen for patients with ≥4th-line GIST that progressed following treatment with ripretinib 150 mg QD”- investigators concluded. -Alexis Hyams