TY - JOUR
T1 - Phase I/IIa, open-label, multicentre study to evaluate the optimal dosing and safety of ODM-203 in patients with advanced or metastatic solid tumours
AU - Bono, Petri
AU - Massard, Christophe
AU - Peltola, Katriina J.
AU - Azaro, Analía
AU - Italiano, Antoine
AU - Kristeleit, Rebecca S.
AU - Curigliano, Giuseppe
AU - Lassen, Ulrik
AU - Arkenau, Hendrik Tobias
AU - Hakulinen, Pasi
AU - Garratt, Chris
AU - Ikonen, Tarja
AU - Mustonen, Mika V.J.
AU - Rodon, Jordi A.
N1 - Funding Information:
Acknowledgements The authors would like to thank all patients and their families, and all sites and their staff for participating in this trial. Medical writing assistance was provided by Rachel Bell, Bioscript Group, Macclesfield, UK, and funded by Orion Pharma. Contributors Authors (PB, CM, KJP, PH, CG, TI, MVJM and JAR) contributed to and were involved in the conception and design of the study, provision of study materials or patients (PB, CM, KJP, AA, AI, RSK, GC, UL and H-TA), collection and assembly of data, data analysis and interpretation, and paper writing (PB, CM, KJP, PH, CG, TI, MVJM and JAR). All authors (PB, CM, KJP, AA, AI, RSK, GC, UL, H-TA, PH, CG, TI, MVJM and JAR) read and approved the final paper.
Funding Information:
The study was sponsored by Orion Corporation, Orion Pharma, Espoo,
Funding Information:
Competing interests PB reports personal fees from Orion Pharma, during the conduct of the study, personal fees from Bristol-Myers Squibb, MSD, Pfizer, Novartis, EUSA, Oncorena, TILT Biotherapeutics, Faron Pharmaceuticals, Ipsen and Herantis Pharma, outside the submitted work, and stock ownership: TILT Biotherapeutics and Terveystalo. At the time of the study PB was employed by Helsinki University Hospital. CM reports consultant/advisory fees from Amgen, Astellas, Astra Zeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, MSD, Novartis, Pfizer, Roche, Sanofi, Orion, outside the submitted work, he is also principal/sub-Investigator of clinical trials for Abbvie, Aduro, Agios, Amgen, Argen-x, Astex, AstraZeneca, Aveo pharmaceuticals, Bayer, Beigene, Blueprint, BMS, Boeringer Ingelheim, Celgene, Chugai, Clovis, Daiichi Sankyo, Debiopharm, Eisai, Eos, Exelixis, Forma, Gamamabs, Genentech, Gortec, GSK, H3 biomedecine, Incyte, Innate Pharma, Janssen, Kura Oncology, Kyowa, Lilly, Loxo, Lysarc, Lytix Biopharma, Medimmune, Menarini, Merus, MSD, Nanobiotix, Nektar Therapeutics, Novartis, Octimet, Oncoethix, Oncopeptides AB, Orion, Pfizer, Pharmamar, Pierre Fabre, Roche, Sanofi, Servier, Sierra Oncology, Taiho, Takeda, Tesaro, Xencor. KJP reports personal fees from MSD, BMS, Roche Pfizer, Varian and Ipsen, outside the submitted work, and stock ownership: Faron Pharmaceuticals. At the time of the study KJP was employed part time (6 months) by Orion Pharma. AA reports personal fees from Orion Pharma and Amcure, outside the submitted work. AI reports research grants and personal fees from Ipsen, Novartis, Bayer, Bristol-Myers Squibb, Epizyme, Immune Design, Daiichi Sankyo and MSD outside the submitted work. GC reports personal fees from Roche, Seattle Genetics, Daichii Sankyo, AstraZeneca and Lilly, and other from Roche and Pfizer outside the submitted work. UL reports personal fee from Bayer and Pfizer outside the submitted work, and research grants from Roche, BMS, Pfizer and GSK. H-TA is an employee of HCAHealthcare UK/Sarah Cannon and reports receiving speaker bureau honoraria from Pierre Fabre, Guardant, BeiGene, and Roche outside the submitted work. PH, CG, TI and MVJM were employed by Orion. JAR reports personal fees and other from Novartis, Kelun Pharmaceuticals/Klus Pharma, Spectrum Pharmaceuticals Inc., Pfizer and Bayer, personal fees from Eli Lilly, Orion Pharmaceuticals, Peptomyc, Roche Pharmceuticals, Ellipses Pharma, Certera, and Ionctura SA, and other from European Journal of Cancer, VHIO/ Ministero De Empleo Y Seguridad Social, Chinese University of Hong Kong, SOLTI, Elsevier, GlaxoSmithKline, ESMO, Department of Defense, Merck Sharp & Dohme, Lousiania State University, Huntsman Cancer Institute, Cancer Core Europe, Karolinska Cancer Institute, King Abdullah International Medical Research Center, WIN Consortium, Janssen, Tocagen, Symphogen, BioAlta, GenMab, CytomX, Kelun-Biotech, Takea-Millenium, and Ipsen outside the submitted work.
Publisher Copyright:
© 2020 Author (s).
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Background: Genetic alterations in fibroblast growth factor receptor (FGFR) and vascular endothelial growth factor receptor (VEGFR) signalling are observed in various tumours. We report a first-in-human phase I/IIa trial evaluating tolerability, pharmacokinetics and preliminary antitumour activity of ODM-203, a novel FGFR and VEGFR inhibitor. Methods: Open-label, non-randomised, multicentre, phase I/IIa dose escalation and expansion study in patients with advanced or metastatic solid tumours. Results: Overall, 84 patients received treatment; optimal tablet dose was found to be 400 mg/day with food. All patients experienced at least one adverse event; the majority (89.2%) were grade 1 or 2% and 70.4% were considered treatment related. The most commonly reported events were bilirubin increase-related events (75%) and diarrhoea (50%). Overall response rate was 9.2% and median progression-free survival was 16.1 and 12.4 weeks for patients with aberrant or non-aberrant FGFR tumours. Median time on treatment was 10.1 weeks for all patients and 14.5 weeks for patients who received 400 mg tablets. Conclusion: This study suggests ODM-203 400 mg/day results in sufficient plasma concentrations and acceptable tolerability in most patients. Preliminary signs of therapeutic activity of ODM-203 in patients with solid tumours was observed.
AB - Background: Genetic alterations in fibroblast growth factor receptor (FGFR) and vascular endothelial growth factor receptor (VEGFR) signalling are observed in various tumours. We report a first-in-human phase I/IIa trial evaluating tolerability, pharmacokinetics and preliminary antitumour activity of ODM-203, a novel FGFR and VEGFR inhibitor. Methods: Open-label, non-randomised, multicentre, phase I/IIa dose escalation and expansion study in patients with advanced or metastatic solid tumours. Results: Overall, 84 patients received treatment; optimal tablet dose was found to be 400 mg/day with food. All patients experienced at least one adverse event; the majority (89.2%) were grade 1 or 2% and 70.4% were considered treatment related. The most commonly reported events were bilirubin increase-related events (75%) and diarrhoea (50%). Overall response rate was 9.2% and median progression-free survival was 16.1 and 12.4 weeks for patients with aberrant or non-aberrant FGFR tumours. Median time on treatment was 10.1 weeks for all patients and 14.5 weeks for patients who received 400 mg tablets. Conclusion: This study suggests ODM-203 400 mg/day results in sufficient plasma concentrations and acceptable tolerability in most patients. Preliminary signs of therapeutic activity of ODM-203 in patients with solid tumours was observed.
KW - dose escalation study
KW - FGFR and VEGFR inhibitor
KW - ODM-203
KW - phase I
KW - solid tumours
UR - http://www.scopus.com/inward/record.url?scp=85097034289&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85097034289&partnerID=8YFLogxK
U2 - 10.1136/esmoopen-2020-001081
DO - 10.1136/esmoopen-2020-001081
M3 - Article
C2 - 33262202
AN - SCOPUS:85097034289
VL - 5
JO - ESMO Open
JF - ESMO Open
SN - 2059-7029
IS - 6
M1 - e001081
ER -