Safety and pharmacokinetics of imaradenant (AZD4635) in Japanese patients with advanced solid malignancies: a phase I, open-label study.

Autor: Matsubara, Nobuaki, Kusuhara, Shota, Yamamoto, Noboru, Sudo, Kazuki, Yanagita, Masahiko, Murayama, Kosho, Kawasumi, Hisashi, Russell, Deanna L., Yin, Da, Shimizu, Toshio
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Zdroj: Cancer Chemotherapy & Pharmacology; Apr2024, Vol. 93 Issue 4, p341-352, 12p
Abstrakt: Purpose: Imaradenant is a novel potent and selective adenosine A2A receptor antagonist that is hypothesized to reduce immune suppression in the tumor microenvironment. This phase I, open-label, dose-escalation study evaluated the safety, pharmacokinetics, and anti-tumor activity of imaradenant. Methods: Japanese patients with advanced solid malignancies received imaradenant 50 mg (n = 3) or 75 mg (n = 7) once daily (QD). The primary objective was safety and tolerability, and the secondary objectives were pharmacokinetics and anti-tumor activity. Results: The median treatment duration was 2.10 months and 2.14 months for the 50- and 75-mg QD cohorts, respectively. The most common adverse events were nausea, malaise, decreased appetite, and vomiting. Five patients (50%) reported adverse events that were considered causally related to imaradenant; three patients had Grade 2 adverse events of malaise, nausea, and diarrhea. No deaths or serious adverse events occurred. The median times of maximum observed concentrations sampled after a single dose in the 50- and 75-mg QD cohorts were 1.08 h (range, 0.95–1.95) and 2.00 h (range, 0.92–5.52), respectively. There was little accumulation after multiple dosing, with geometric mean accumulation ratios of maximum concentration of 1.3 (50-mg QD) to 1.4 (75-mg QD) and area under the concentration–time curve 0–24 of 1.4 (50-mg QD) to 1.5 (75-mg QD). The best objective response was stable disease (3/10). Conclusion: No new or unexpected safety concerns were identified, and imaradenant had an acceptable safety profile at both 50- and 75-mg QD. ClinicalTrials.gov identifier NCT03980821 (June 10, 2019). [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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