Repotrectinib
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| ID | DRUG-REPOTRECTINIB |
|---|---|
| Tipo | Fármaco |
| Alegais | ÁguiaTPX-0005Репотректініб |
| Estado | reviewed 2026-04-27 | pending_clinical_signoff |
| Doenças | DIS-NSCLC |
| Fontes | SRC-ESMO-NSCLC-METASTATIC-2024 SRC-NCCN-NSCLC-2025 |
Fatos sobre as drogas
| Classe | Inibidor da tirosina quinase da tirosina de próxima geração ROS1 / NTRK / ALK |
|---|---|
| Mecanismo | Macrocyclic next-generation ATP-competitive small-molecule TKI designed with a compact rigid scaffold to fit the kinase active site even when bulky solvent-front mutations (ROS1 G2032R, NTRK1 G595R, NTRK3 G623R) confer resistance to first-generation TKIs (crizotinib, entrectinib, larotrectinib). Inhibits ROS1, NTRK1/2/3, and ALK with sub-nanomolar potency including against the resistance mutations. CNS-penetrant (CSF/plasma free-fraction ratio favorable) → meaningful intracranial response. Pivotal evidence TRIDENT-1: ROS1+ NSCLC TKI-naive ORR ~79% (mDOR ~34 mo), post-crizotinib ORR ~38% (active vs G2032R); NTRK fusion solid tumors TKI-pretreated ORR ~50%. FDA approvals Nov 2023 (ROS1 NSCLC) and June 2024 (tumor-agnostic NTRK fusion). |
| Dose típica | Pload-in: 160 mg PO uma vez por dia durante 14 dias, depois escalar para 160 mg PO bid contínuo até progressão / toxicidade inaceitável. O Plood-in mitiga tonturas e outros efeitos adversos do SNC (BID começar sem Ploed-in piora significativamente neurologic AE). Tomar com ou sem alimentos (efeito moderado). Nível de dose -1 = 120 mg BID; -2 = 80 mg BD; -3 = 80mg diário; interrupção permanente se G3-4 recorrente. Evitar em compromisso hepático grave. |
| Ucrânia registada | Falso |
| NSZU reembolsado | Falso |
| Ucrânia verificada pela última vez | 2026-04-27 |
Notas
Lead-in dosing schedule (14 days at 160 mg daily before BID) is critical — initiating at the full BID dose causes substantially more dizziness, ataxia, and cognitive AEs. Active against G2032R ROS1 (the dominant crizotinib-resistance mutation) and against G595R/G623R NTRK solvent-front mutations — making it the preferred agent post-crizotinib (ROS1) or post-larotrectinib/entrectinib (NTRK). CNS adverse events typically peak first weeks and improve with dose adjustments. Counsel patients on driving / operating machinery. Baseline workup: LFTs, CK, urate, ECG, brain MRI (baseline for ROS1+/NTRK+ given high CNS metastasis incidence), pregnancy test. Monitor LFTs q2 wks first 8 wks then monthly, uric acid first cycle, neurologic exam each visit. In contemporary practice repotrectinib has displaced crizotinib for ROS1 1L where access permits (TRIDENT-1 mPFS not reached vs crizotinib historical ~19 mo).
Usado por
Esquema terapêutico
REG-REPOTRECTINIB-NSCLC- Repotrectinib em monoterapia (TRIDENT-1) — ROS1+ NSCLC (TKI- nativo ou pós-prior ROS1-TKI)REG-REPOTRECTINIB-NTRK-PAN-TUMOR- Repotrectinib em monoterapia (TRIDENT-1) — tumores sólidos NTRK-fusion+ (pan-tumor, TKI-naive o...