Ono opens Japan enrollment for ripretinib in 4th-line GIST
The Phase 1 safety study revives ripretinib in heavily pretreated GIST patients even as the same drug's own Phase 3 trial against sunitinib missed its progression-free survival endpoint.
Executive Summary
- Ono Pharmaceutical opened enrollment for a Phase 1 study testing ripretinib in Japanese patients with gastrointestinal stromal tumor who have already failed at least three prior treatment lines.
- Ripretinib is already an approved therapy in later-line GIST, so this study is a bridging safety read for a Japanese population rather than a test of a new mechanism.
- The same drug's pivotal trial against sunitinib in an earlier treatment line did not show the survival benefit it was designed to demonstrate, a result that frames how much weight this smaller study can carry.
- The trial's single endpoint is adverse-event incidence, making tolerability, not efficacy, the information this readout can deliver.
The status change
The trial, registered as NCT07618377, shifted its ClinicalTrials.gov status from Not yet recruiting to Recruiting, with a first patient visit window that started July 7, 2026. The study targets 10 patients across sites in Japan and carries a primary completion date of February 1, 2028. Enrollment held flat at its original target of 10, a routine outcome for an early-phase safety cohort and not a signal the operational model flags. NCT07618377Study of DCC-2618 in Patients With GIST After at Least 3 Prior TreatmentsNCT07618377
Probability of SuccessBased on the AppliedXL Probability of Success model. For more information about the methodology, read the research here.
What the trial tests
The study enrolls patients with a histologically confirmed GIST diagnosis who are refractory or intolerant to at least imatinib, sunitinib, and regorafenib, restricting the population to those who have already failed the standard sequence of approved therapies. Its single primary endpoint is adverse-event incidence, tracked over up to two years, with no comparator arm and open-label dosing in a single-arm design. That design makes the readout a tolerability question in a fourth-line-plus Japanese population, not an efficacy comparison. NCT07618377Study of DCC-2618 in Patients With GIST After at Least 3 Prior TreatmentsNCT07618377
The drug's own record
Ripretinib is FDA-approved as QINLOCK, an oral kinase inhibitor for GIST, with an NDA already on file. The drug's Phase 3 INTRIGUE trial, which compared ripretinib against sunitinib in patients previously treated with imatinib, did not meet its primary endpoint of improved progression-free survival, sponsor Deciphera Pharmaceuticals disclosed in November 2021. That result sits against a second Phase 2 trial of the same drug that did meet its primary endpoint, so the drug's track record in GIST is mixed: one Phase 1/2 program withdrawn, two completed trials, and one Phase 3 miss on record.
The competitive field
GIST now carries a field of KIT-targeted small molecules beyond ripretinib, including Blueprint Medicines Corporation's avapritinib, already in a Phase 4 trial, and two later-stage KIT inhibitors advancing toward pivotal data: GlaxoSmithKline's velzatinib in Phase 3 and Deciphera Pharmaceuticals' next-generation candidate DCC-3009 in Phase 1/2. Ono's own portfolio in GIST includes ripretinib trials at Phase 3 (active, not recruiting), Phase 1/2 (withdrawn), and multiple completed Phase 1 and Phase 2 studies, alongside this newly recruiting Phase 1 safety cohort. Ono has run 93 trials with an 89% completion rate, and one of its prior ripretinib programs, a Phase 1/2 combination study with binimetinib, was withdrawn in November 2025. NCT07618377Study of DCC-2618 in Patients With GIST After at Least 3 Prior TreatmentsNCT07618377
Readthrough
Because ripretinib already holds approval, the bar this study needs to clear is replication of an established tolerability profile in a fourth-line-plus Japanese population, not a new efficacy signal. A safety result consistent with the drug's existing label would support continued use in this heavily pretreated group; a drift toward higher toxicity than seen in prior ripretinib studies would be the more consequential outcome to watch given the population's exhausted treatment options. NCT07618377Study of DCC-2618 in Patients With GIST After at Least 3 Prior TreatmentsNCT07618377
This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.