Ripretinib
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | DRUG-RIPRETINIB |
|---|---|
| Type | Drug |
| Aliases | QinlockРипретиніб |
| Status | reviewed 2026-04-29 | pending_clinical_signoff |
| Diseases | DIS-GIST |
| Sources | SRC-CIVIC SRC-INVICTUS SRC-NCCN-GIST-2025 |
Drug Facts
| Class | Broad-spectrum switch-control KIT/PDGFRA tyrosine kinase inhibitor |
|---|---|
| Mechanism | First-in-class KIT/PDGFRA switch-control inhibitor that uses a dual-mechanism: it locks the kinase activation loop in the inactive conformation by binding both the switch pocket (αC-out) and the activation loop, broadly inhibiting primary exon 9/11/17 KIT mutations AND secondary resistance mutations across exons 13/14/17/18 — the vulnerability gap left by sequential prior TKIs (imatinib → sunitinib → regorafenib). Pivotal INVICTUS Phase III (4L+ advanced GIST, ripretinib 150 mg QD vs placebo) showed mPFS 6.3 vs 1.0 months (HR 0.15, p<0.0001) and mOS 15.1 vs 6.6 months (HR 0.36); FDA approval May 2020. |
| Typical dosing | 150 mg PO once daily, with or without food, until disease progression or unacceptable toxicity. Intra-patient dose escalation to 150 mg twice daily on progression is supported by INTRIGUE post-hoc and the INSIGHT Phase III (positive vs sunitinib in PDGFRA D842V-negative, KIT exon 11 + 17/18 mutated 2L). Dose modifications: hold for grade ≥3 hand-foot syndrome, hypertension, cardiac dysfunction (LVEF drop), or severe rash; resume at 100 mg QD. |
| Ukraine registered | False |
| NSZU reimbursed | False |
| Ukraine last verified | 2026-04-29 |
Notes
FDA approval (May 2020) for 4L+ advanced GIST after ≥3 prior kinase inhibitors (imatinib → sunitinib → regorafenib). NCCN-GIST 2025 lists ripretinib as preferred 4L (category 1). The INTRIGUE Phase III (ripretinib 150 mg QD vs sunitinib 50 mg 4-on/2-off in 2L GIST) failed its 2L primary endpoint (mPFS 8.0 vs 8.3 mo, HR 1.05, NS) but pre-specified KIT exon 11 + 17/18 ctDNA subgroup showed a striking ripretinib benefit (mPFS 14.2 vs 1.5 mo) — INSIGHT Phase III is the confirmatory study in this genotype-defined 2L population. Cardiac surveillance (LVEF) and dermatologic surveillance (cutaneous SCC) are ongoing-treatment requirements. Missing trial-source IDs to flag for follow-up: SRC-INVICTUS exists as a stub awaiting clinical signoff; SRC-INTRIGUE, SRC-INSIGHT, SRC-FDA-QINLOCK not yet authored.
Used By
Regimens
REG-RIPRETINIB-GIST-4L- Ripretinib monotherapy (advanced GIST, ≥4L after imatinib + sunitinib + regorafenib)