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

Debbie Robbrecht, J Lopez, E Calvo, X He, H Hiroshi, N Soni, N Cook, A Dowlati, A Fasolo, V Moreno, Ferry Eskens, JS de Bono

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12 Citations (Web of Science)

Abstract

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/β-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. Clinical trial registration: NCT02448589.

Original languageEnglish
Pages (from-to)391-398
Number of pages8
JournalBritish Journal of Cancer
Volume124
Issue number2
DOIs
Publication statusPublished - 19 Jan 2021

Research programs

  • EMC OR-01

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