DS-6051b is an orally administered inhibitor of the tyrosine kinases (ROS1) and neurotropic tyrosine kinase receptors (NTRK). This phase 1 first-in-human study evaluates safety and tolerability of DS-6051b in cancer subjects and identify a recommended phase 2 dose (RP2D). In addition, this study will also assess the pharmacokinetic (PK)/pharmacodynamic (PD) profiles and preliminary efficacy of DS-6051b.
The Dose Escalation part (Part 1) of this study will evaluate safety and tolerability, and determine the tentative RP2D. Plasma exposure of DS-6051a and the exposure - QT interval prolongation relationship will also be assessed. Approximately 30 subjects with advanced solid tumors harboring ROS1 or NTRK1, NTRK2, or NTRK3 rearrangement, neuroendocrine carcinoma, or with advanced solid tumors and tumor-induced pain will be enrolled. The Food Effect (FE) part of this study is to determine the effect of food on the PK of DS-6051a following administration of a single oral dose of DS-6051b. The safety and tolerability of DS-6051b administered with or without food will also be assessed. After the safety profile of DS-6051b is adequately evaluated, the Dose Expansion part (Part 2) will be initiated to further assess the safety and tolerability, and preliminarily evaluate the efficacy of DS-6051b at the tentative RP2D. Approximately 40 cancer subjects carrying a ROS1 or NTRK1, NTRK2, or NTRK3 rearrangement will be enrolled.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
46
DS-6051b 50 mg and 200 mg capsules for oral administration
HonorHealth Research Institute
Scottsdale, Arizona, United States
Chao Family Comprehensive Cancer Center of
Orange, California, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Dana Farber Cancer Inst.
Boston, Massachusetts, United States
Part 1: Number of participants with dose-limiting toxicities
Time frame: within 21 days following the first dose of treatment
Tumor response
Tumor response will be assessed using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
Time frame: up to 2 years
Maximum concentration (Cmax) for DS-6051a
Time frame: At Days 1 and 15 of Cycle 1 (21 days)
Time to maximum concentration (Tmax) for DS-6051a
Time frame: At Days 1 and 15 of Cycle 1 (21 days)
Area under the concentration-time curve from time zero to t (AUC0-t) for DS-6051a
Time frame: At Days 1 and 15 of Cycle 1 (21 days)
Change from baseline in QTc interval
ECGs performed to assess QTc interval (ms) at baseline and on study treatment and at the end of treatment visit.
Time frame: within 2 years
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New York University
New York, New York, United States
South Texas Accelerated Research Therapeutics
San Antonio, Texas, United States