A phase 1/2 study of NS-87/CPX-351 (cytarabine and daunorubicin liposome) in Japanese patients with high-risk acute myeloid leukemia

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2024年3月26日

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Kensuke Usuki,
Toshihiro Miyamoto,
Takuji Yamauchi,
Kiyoshi Ando,
Yoshiaki Ogawa,
Masahiro Onozawa,
Takahiro Yamauchi,
Hitoshi Kiyoi,
Akira Yokota,
Takayuki Ikezoe,
Yuna Katsuoka,
Satoru Takada,
Nobuyuki Aotsuka,
Yasuyoshi Morita,
Takayuki Ishikawa,
Noboru Asada,
Shuichi Ota,
Atsushi Dohi,
Kensaku Morimoto,
Shunji Imai,
Umi Kishimoto,
Koichi Akashi,
Yasushi Miyazaki,
Junya Kuroda,
Hiroatsu Iida,
Naohiro Sekiguchi,
Katsuto Takenaka,
Toshiro Kawakita,
Kazunori Imada,
Takahiro Suzuki,
Shuichi Miyawaki,
Noriko Usui,
Norio Asou,
Masakazu Muta,
Kazuto Tsuruda,
Masafumi Taniwaki,
Masatoshi Fujita,
Hideki Makishima,
Yoko Nakanishi,
Masaya Tajima,
Yutaka Masutomi,
Masahiro Chiba,
Mayuna Hokazomo,
Shihomi Hirooka,
Taisuke Mikasa,
Moemi Okamoto,
Akitaka Kawase,
Akane Yamada,
Yuto Shimizu,
Kento Isogaya,
Tomohiko Ichikawa

摘要

Objectives

NS-87/CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin. NS-87/CPX-351 exerts antileukemic action by maintaining a synergistic molar ratio of cytarabine to daunorubicin of 5:1 within the liposome while in circulation. Patients with high-risk acute myeloid leukemia (AML), which includes therapy-related AML and AML with myelodysplasia-related changes (AML-MRC), have poorer outcomes than those with other AML.

Methodology

This open-label phase 1/2 (P1/2) study was conducted in 47 Japanese patients aged 60–75 years with newly diagnosed high-risk AML to evaluate the pharmacokinetics, safety, and efficacy of NS-87/CPX-351.

Results

In the 6 patients enrolled in the P1 portion, no dose-limiting toxicities (DLTs) were reported, and 100 units/m² during the induction cycle was found to be acceptable. Cytarabine and daunorubicin had a long half-life in the terminal phase (32.8 and 28.7 h, respectively). In the 35 patients enrolled in the P2 portion, composite complete remission (CRc; defined as complete remission [CR] or CR with incomplete hematologic recovery [CRi]) was achieved in 60.0% (90% CI: 44.7–74.0) of the patients. Adverse events due to NS-87/CPX-351 were well tolerated.

Outcomes

NS-87/CPX-351 can be considered as a frontline treatment option for Japanese patients with high-risk AML.