A phase 1/2 study of gilteritinib in combination with chemotherapy in newly diagnosed patients with AML in Asia

期刊论文
出版模式：

开放获取
发表日期：

2024年11月6日

查看全文

Masashi Sawa,
Toshihiro Miyamoto,
Hee-Je Kim,
Yasushi Hiramatsu,
June-Won Cheong,
Takayuki Ikezoe,
Tomoki Naoe,
Koichi Akashi,
Satoshi Morita,
Masanori Kosako,
Moyu Ikegaya,
Wataru Terada,
Takeshi Kadokura,
Jason Hill,
Shuichi Miyawaki,
Stanley C. Gill,
Alexandra Heinloth,
Nahla Hasabou

摘要

Objective

This interim analysis of a phase 1/2, open-label, single-arm study assessed the safety, efficacy, and pharmacokinetics of gilteritinib plus chemotherapy in adults with newly diagnosed FLT3 mutation-positive acute myeloid leukemia.

Methods

In sequential phase 1 and 2 studies, induction and consolidation therapy with gilteritinib 120 mg/day plus chemotherapy (induction: idarubicin/cytarabine once daily; consolidation: cytarabine twice daily) was followed by maintenance gilteritinib 120 mg/day monotherapy. Endpoints included maximum tolerated dose (MTD), recommended expansion dose (RED), and dose-limiting toxicity (phase 1), and complete remission (CR) rate following induction therapy (primary endpoint), overall survival (OS), safety, and pharmacokinetics (phase 2).

Results

In phase 1, MTD was not reached and RED was 120 mg/day. In phase 2, the CR rate was 50.0% after induction (90% confidence interval [CI] 40.4, 59.6); however, the lower confidence limit did not exceed the pre-defined 55% benchmark. Composite CR (CRc) rates were high following induction (86.6%, 95% CI [77.3, 93.1]), consolidation, and maintenance therapy (87.8%, 95% CI [78.7, 94.0], each). The probability of OS was 86.6% at 12 months. No new safety findings were reported.

Conclusion

In this interim analysis, gilteritinib 120 mg/day in combination with chemotherapy was well tolerated, with similar CRc rates to previous studies.