Repotrectinib
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | DRUG-REPOTRECTINIB |
|---|---|
| Type | Drug |
| Aliases | AugtyroTPX-0005Репотректініб |
| Status | reviewed 2026-04-27 | pending_clinical_signoff |
| Diseases | DIS-NSCLC |
| Sources | SRC-ESMO-NSCLC-METASTATIC-2024 SRC-NCCN-NSCLC-2025 |
Drug Facts
| Class | Next-generation ROS1 / NTRK / ALK tyrosine kinase inhibitor |
|---|---|
| Mechanism | 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). |
| Typical dosing | Lead-in: 160 mg PO once daily for 14 days, then escalate to 160 mg PO BID continuous until progression / unacceptable toxicity. The lead-in mitigates dizziness and other CNS adverse effects (BID start without lead-in significantly worsens neurologic AE). Take with or without food (modest effect). Dose level -1 = 120 mg BID; -2 = 80 mg BID; -3 = 80 mg daily; permanent discontinuation if recurrent G3-4. Avoid in severe hepatic impairment. |
| Ukraine registered | False |
| NSZU reimbursed | False |
| Ukraine last verified | 2026-04-27 |
Notes
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).
Used By
Regimens
REG-REPOTRECTINIB-NSCLC- Repotrectinib monotherapy (TRIDENT-1) — ROS1+ NSCLC (TKI-naive or post-prior ROS1-TKI)REG-REPOTRECTINIB-NTRK-PAN-TUMOR- Repotrectinib monotherapy (TRIDENT-1) — NTRK-fusion+ solid tumors (pan-tumor, TKI-naive o...