This is a First-in-Human (FIH), 2-part, Phase 1/2, open-label, multicenter study design to evaluate the safety, tolerability, PK, pharmacodynamics, PGx, and efficacy of TAS0728. This study consists of Phase 1 and Phase 2 components in subjects with advanced solid tumors with HER2 or HER3 overexpression, amplification, or mutation who have progressed despite standard therapy or for which no standard therapy exists, particularly urothelial cancer, biliary tract cancer, metastatic breast cancer, non-small cell lung cancer and colorectal cancer.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
19
TAS0728 is an oral HER2 covalent inhibitor investigated in patients with advanced solid tumor harboring HER2 or HER3 abnormalities. It will be administered orally at a starting dose of 50 mg BID each morning and evening and escalated to the DLT. The MTD will be used for the phase 2 arms of the study.
City of Hope Comprehensive Cancer Center
Duarte, California, United States
Winship Cancer Institute
Atlanta, Georgia, United States
Icahn School of Medicine at Mount Sinai
New York, New York, United States
Sarah Cannon
Nashville, Tennessee, United States
University of Texas - MD Anderson
Houston, Texas, United States
Institut de Cancerologie Gustavo Roussy
Paris, France
Hospital Vall D'hebron
Barcelona, Spain
Sarah Cannon Research Institute - UK
London, United Kingdom
Number of patients experiencing Dose Limiting Toxicity graded according to CTCAE Version 4.03, observed in the Cycle 1 in order to meet the objective of assessment of the MTD of TAS0728.
Time frame: 21-day cycles
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] (Phase 1 and 2)
Time frame: Safety monitoring will begin at the informed consent obtained and continue up to 30 days after the last dose of TAS0728 or until new antitumor therapy, whichever is earlier.
Objective Response Rate using Response Evaluation Criteria in Solid Tumors 1.1 (RECIST) (Phase2)
Time frame: 3 years
Maximum Plasma Concentration (Cmax) after administration of TAS0728 (Phase 1)
Time frame: 21 days in Cycle 1
Area under the plasma drug concentration-time curve (AUC) after administration of TAS0728 (Phase 1)
Time frame: 21 days in Cycle 1
Disease Control Rate using RECIST 1.1 (phase 1 and 2)
Time frame: 3 years
Progression free survival (phase 1 and 2)
Time frame: 3 years
Duration of response (phase 1 and 2)
Time frame: 3 years
Overall survival (phase 1 and 2)
Time frame: 3 years
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