Dataset Information

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

ABSTRACT:

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).

SUBMITTER: Matsubara N

PROVIDER: S-EPMC10950984 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Matsubara Nobuaki N Kusuhara Shota S Yamamoto Noboru N Sudo Kazuki K Yanagita Masahiko M Murayama Kosho K Kawasumi Hisashi H Russell Deanna L DL Yin Da D Shimizu Toshio T

Cancer chemotherapy and pharmacology 20231213 4

<h4>Purpose</h4>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.<h4>Methods</h4>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 sec ...[more]

PMID: 38086998

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Dataset Information

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

Purpose

Methods

Results

Conclusion

Clinicaltrials

Publications

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

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