A first-in-human phase I study of TAS0728, an oral covalent binding inhibitor of HER2, in patients with advanced solid tumors with HER2 or HER3 aberrations
Year: 2021
Type: article
Study design: Clinical Trial
Abstract: TAS0728 is an oral covalent binding inhibitor of human epidermal growth factor receptor 2 (HER2). A first-in-human open-label, dose-escalation, phase I study (NCT03410927) was initiated to investigate the safety and dose-limiting toxicity (DLT) and to determine the maximum tolerated dose (MTD) and/or recommended phase II dose of TAS0728 in adults with advanced solid tumors with HER2 or HER3 overexpression, amplification or mutation. In total, 19 patients received TAS0728 at escalating doses from 50 to 200 mg BID for 21-day cycles. Following escalation of the dose to 200 mg BID, a total of two DLTs were observed, both cases of Grade 3 diarrhea (lasting >48 h and not responsive to aggressive antidiarrheal treatment). Following de-escalation of the dose to 150 mg BID, another DLT of Grade 3 diarrhea was observed in one patient. Additionally, at 150 mg BID, one patient had a fatal cardiac arrest after receiving 1 cycle (21 days) of TAS0728. The etiology of the cardiac arrest event was not clear, however causal relationship to TAS0728 could not be excluded due to the temporal association observed. Partial responses were observed in 2 of 14 patients evaluable for TAS0728 treatment response. The study was stopped due to unacceptable toxicity during the dose-escalation as the overall risk-benefit ratio no longer favored the dose level being tested, therefore the MTD was not determined. ClinicalTrials.gov registration number: https://clinicaltrials.gov/ct2/show/NCT03410927 ; registered on January 25, 2018.
Source: Investigational New Drugs
Institutions: University College Hospital, The University of Texas MD Anderson Cancer Center, Sarah Cannon Research Institute, Vall d'Hebron Institute of Oncology, University College London, Seoul National University, Seoul National University Hospital, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, City Of Hope National Medical Center, Taiho Oncology (United States), Institut Gustave Roussy
Language: English
Topic: HER2/EGFR in Cancer Research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,860
Funders: Amgen, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, AstraZeneca, GlaxoSmithKline, BioMarin Pharmaceutical, Exelixis, Five Prime Therapeutics, INOVIO Pharmaceuticals, BeiGene, Incyte, Aminex Therapeutics, Puma Biotechnology, Silverback Therapeutics, UroGen Pharma, Eisai, Astellas Pharma, Servier, Ipsen, National Institutes of Health, Genentech, EMD Serono, Merck Sharp and Dohme, Chugai Pharmaceutical, Principia Biopharma, National Cancer Institute, National Center for Advancing Translational Sciences, Daiichi Sankyo Europe
OpenAlex ID: W3147596801