A phase 1 study to assess the absolute bioavailability, mass balance, pharmacokinetics, metabolism, and excretion of [14C]-mobocertinib, an oral inhibitor of EGFR exon 20 insertion mutations, in healthy participants

• DOI: 10.1007/s10637-024-01446-y
• Publication Date: 2024-05-24T20:20:53Z
• Authors: Michael J. Hanley; Steven Zhang; Robert Griffin; Sean Xiaochun Zhu; Robert J. Fram; Jianchang Lin; Karthik Venkatakr...; Neeraj Gupta
• Keywords: Male; Adult; Aniline Compounds; Indoles; Research; Biological Availability; Administration, Oral; Exons; Middle Aged; Healthy Volunteers; ErbB Receptors; Young Adult; Mutagenesis, Insertional; 03 medical and health sciences; Pyrimidines; 0302 clinical medicine; Humans; Carbon Radioisotopes; Protein Kinase Inhibitors

Abstract Mobocertinib (TAK-788) is a first-in-class oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that received accelerated approval for the treatment of patients with non-small cell lung cancer EGFR exon 20 insertion mutations previously treated platinum-based chemotherapy. This phase 1, 2-period, study was conducted to assess absolute bioavailability mobocertinib (Period 1), as well mass balance, pharmacokinetics, metabolism, and excretion [ 14 C]-mobocertinib 2) in healthy adult males. In Period participants single capsule dose 160 mg mobocertinib, followed by 15-minute intravenous infusion 50 µg (~ 2 µCi) administered from 3.75 4 h after dose. 2, 100 an solution. The geometric mean determined be 36.7%. After administration C]-mobocertinib, its active metabolites, AP32960 AP32914, were minor components plasma, accounting only 0.275% total plasma radioactivity majority mobocertinib-related material covalently bound proteins. percentage radioactive recovered urine feces 3.57% 76.0%, respectively. Only 0.39% mobocertinib; thus, indicating renal unchanged drug very pathway elimination. both periods, generally safe well-tolerated all adverse events Grade 1 severity. ( Trial registration number ClinicalTrials.gov NCT03811834. Registration date January 22, 2019).