A Phase 1 Study of Sapanisertib (TAK-228) in East Asian Patients with Advanced Nonhematological Malignancies
Journal
Targeted Oncology
Journal Volume
17
Journal Issue
1
Pages
15-24
Date Issued
2022
Author(s)
Shimizu T.
Kuboki Y.
Yonemori K.
Yanai T.
Faller D.V.
Dobler L.
Gupta N.
Sedarati F.
Kim K.-P.
Abstract
BACKGROUND: Sapanisertib is an oral, highly selective inhibitor of mammalian target of rapamycin complexes 1 and 2. OBJECTIVE: The aim of this study was to assess the safety, tolerability, pharmacokinetics, preliminary efficacy, and to establish the recommended phase 2 dose (RP2D) of sapanisertib. PATIENTS AND METHODS: In this dose-escalation and expansion study, East Asian patients with nonhematologic malignancies received increasing sapanisertib doses once-daily (QD; starting at 2 mg) or once-weekly (QW; starting at 20 mg) in 28-day cycles. RESULTS: was ~ 5.9-7.6 h. Three patients achieved stable disease for ≥ 6 months (1 each in 3 mg QD, 4 mg QD and 20 mg QW cohorts, respectively); the clinical benefit rate was 45% and 67% in the QD and QW arms, respectively. CONCLUSIONS: The RP2D of sapanisertib in East Asian patients (3 mg QD) was lower than in Western patients (4 mg QD), but the pharmacokinetics and safety profiles were similar. Sapanisertib was well tolerated and showed moderate anti-tumor effects in heavily pretreated patients with nonhematologic malignancies. NCT NUMBER: NCT03370302; Registered December 7, 2017.
SDGs
Publisher
Adis
Type
journal article