A first-in-human phase 1 and pharmacological study of TAS-119, a novel selective Aurora A kinase inhibitor in patients with advanced solid tumours
Authors
Robbrecht, D. G. J.Lopez, J.
Calvo, E.
He, X.
Hiroshi, H.
Soni, N.
Cook, Natalie
Dowlati, A.
Fasolo, A.
Moreno, V.
Eskens, F.
de Bono, J. S.
Affiliation
Erasmus MC Cancer Institute, Rotterdam, the Netherlands.Issue Date
2020
Metadata
Show full item recordAbstract
Background: This is a first-in-human study with TAS-119, an Aurora A kinase (AurA) inhibitor. Methods: Patients with advanced, refractory, solid tumours were enrolled into 5 dose escalation cohorts (70-300 mg BID, 4 days on/3 days off, 3 out of 4 weeks or 4 out of 4 weeks). The expansion part consisted of patients with small-cell lung cancer, HER2-negative breast cancer, MYC-amplified/?-catenin-mutated (MT) tumours or other (basket cohort). Results: In the escalation part (n = 34 patients), dose-limiting toxicities were one grade 3 nausea, two grade 2 and one grade 3 ocular toxicity and a combination of fatigue, ocular toxicity and nausea in one patient (all grade 2) at dose levels of 150, 200, 250 and 300 mg, respectively. Most frequent treatment-related adverse events were fatigue (32%), diarrhoea (24%) and ocular toxicity (24%). Toxicity grade ?3 in ?10% of patients were diarrhoea (15%) and increased lipase (12%). The maximum tolerated dose was 250 mg BID. Due to one additional grade 1 ocular toxicity, the RP2D was set at 200 mg BID (4 days on/3 days off, 3 out of 4 weeks), which was further explored in the expansion part (n = 40 patients). Target inhibition in paired skin biopsies was shown. Conclusions: TAS-119 has a favourable and remarkably distinct safety profile from other AurA inhibitors.Citation
Robbrecht DGJ, Lopez J, Calvo E, He X, Hiroshi H, Soni N, et al. A first-in-human phase 1 and pharmacological study of TAS-119, a novel selective Aurora A kinase inhibitor in patients with advanced solid tumours. Br J Cancer. 2020.Journal
British Journal of CancerDOI
10.1038/s41416-020-01100-3PubMed ID
33020594Additional Links
https://dx.doi.org/10.1038/s41416-020-01100-3Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1038/s41416-020-01100-3