. 2021 Mar 16;6(2):100087. doi: 10.1016/j.esmoop.2021.100087

Table 1.

Summary of entrectinib clinical trials

Protocol	Study design	Study objectives	Entrectinib dose and regimen	Patient population
ALKA	First-in-human, phase I, multicentre, open-label, dose escalation study	First-cycle DLTs and MTD. Safety, tolerability, PK and antitumour activity	Schedule A: 100, 200, 400, 800, 1200 or 1600 mg/m²/day OD 4-day on, 3-day off schedule for 3 weeks followed by 1-week rest Schedule B: 200 or 400 mg/m²/day or 600 mg/day OD in 4-week cycles Schedule C: 400 or 800 mg/m²/day OD in a continuous 4-day on, 3-day off schedule	Adult patients with advanced/ metastatic solid tumours, including patients with NTRK, ROS1 or ALK molecular alterations
STARTRK-1	Phase I, single-arm, multicentre, open-label, dose escalation and expansion study	Dose escalation: First-cycle DLTs, MTD, RP2D and antitumour activity Dose expansion: ORR, safety, tolerability, PK and PD	Entrectinib OD in a continuous daily dosing regimen in 4-week cycles Doses: 100, 200, 400 mg/m²/day; 800 mg/day; 600 mg/day if BSA ≤ 1.85 m² or 800 mg/day if BSA > 1.85 m²	Adult patients with solid tumours harbouring NTRK, ROS1 or ALK molecular alterations (mandatory for the dose-expansion phase)
STARTRK-2	Phase II, global, single-arm, open-label, multicentre, basket study	Efficacy (CNS separately), safety, tolerability, PK, ventricular repolarisation and patient-reported outcomes	Entrectinib 600 mg OD in a continuous daily dosing regimen in 4-week cycles	Adult patients with solid tumours with NTRK, ROS1 or ALK gene fusions (excluding ALK-positive NSCLC)
STARTRK-NG	Phase I/Ib, single-arm, multicentre, open-label, five-part, dose escalation and expansion study	MTD or RP2D in children and adolescents, safety profile, PK, efficacy parameters, intracranial tumour response in CNS patients	Entrectinib OD in a continuous daily dosing regimen with 4-week cycles. Dosing as per nomogram ranging from 250 to 750 mg/m²/day	Children and young adults (2-22 years) with recurrent or refractory solid tumours and primary CNS tumours, with or without NTRK, ROS1 or ALK molecular alterations

ALK, anaplastic lymphoma kinase; BSA, body surface area; CNS, central nervous system; DLT, dose-limiting toxicity; MTD, maximum tolerated dose; NSCLC, non-small-cell lung cancer; NTRK, neurotrophic tyrosine receptor kinase; OD, once daily; ORR, objective response rate; PD, pharmacodynamics; PK, pharmacokinetics; RP2D, recommended phase II dose.