A Phase 1 study of ARQ 087, an oral pan-FGFR inhibitor in patients with advanced solid tumours
| Autor: | Terence Hall, Yunxia Wang, Bassel F. El-Rayes, Patricia LoRusso, Walid L. Shaib, Jasgit C. Sachdev, Ronald E. Savage, R. D. Harvey, Giovanni Abbadessa, Julia Kazakin, Drew W. Rasco, Amita Patnaik, Brian Schwartz, Kyriakos P. Papadopoulos, Anthony W. Tolcher |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adult Male Cancer Research medicine.medical_specialty Pathology FGFR2 fusion Nausea Administration Oral Gastroenterology 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Internal medicine Neoplasms medicine Adrenocortical carcinoma Humans Dosing Adverse effect Protein Kinase Inhibitors solid tumours Aged Aniline Compounds business.industry Middle Aged medicine.disease Receptors Fibroblast Growth Factor FGFR inhibitor 030104 developmental biology Oncology phase 1 030220 oncology & carcinogenesis Pharmacodynamics Toxicity Cohort Clinical Study Quinazolines Female medicine.symptom business |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | Background: ARQ 087 is an orally administered pan-FGFR inhibitor with multi-kinase activity. This Phase 1 study evaluated safety, pharmacokinetics, and pharmacodynamics of ARQ 087 and defined the recommended Phase 2 dose (RP2D). Methods: Patients with advanced solid tumours received ARQ 087 administered initially at 25 mg every other day and dose-escalated from 25 to 425 mg daily (QD) continuous dosing. FGF19, 21, 23, and serum phosphate were assessed as potential biomarkers of target engagement. Results: 80 patients were enrolled, 61 in dose-escalation/food-effect cohorts and 19 with pre-defined tumour types in the expansion cohort. The most common ARQ 087-related adverse events were fatigue (49%), nausea (46%), aspartate aminotransferase (AST) increase (30%), and diarrhoea (23%). Four patients (5%) experienced grade 1 treatment-related hyperphosphataemia. Dose-limiting toxicity was reversible grade 3 AST increase. The RP2D was 300 mg QD. Pharmacokinetics were linear and dose-proportional from 25 to 325 mg QD, and were unaffected by food. Statistically significant changes (P-value |
| Databáze: | OpenAIRE |
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