PHI-101, a Novel FLT3 TKI, Shows Clinical Efficacy in Relapsed/Refractory FLT3-Mutated AML

作者：Dong‐Yeop Shin, Sung-Soo Yoon, Junshik Hong, Je‐Hwan Lee, Jun‐Ho Jang, June‐Won Cheong, Ho‐Jin Shin, Jeong‐Ok Lee, Yoo Jin Lee, Jae-Sook Ahn, Byoung-Sik Cho, Hee‐Je Kim, Joseph Clarey, Gi‐Jun Sung, Jeejin Im, Ky‐Youb Nam, June‐Chiew Han, Kyu-Tae Kim, JeongHyeok Yoon, Bao Nguyen, Li Li, Donald Small · 发表于：Blood · 年份：2024 · DOI：10.1182/blood-2024-207033 · 被引用次数：2 · 研究领域：Acute Myeloid Leukemia Research、Click Chemistry and Applications、Synthetic Organic Chemistry Methods

Background: We investigated the clinical activity, PK, safety and resistance mechanisms of single-agent PHI-101 in patients (pts) with refractory/relapsed acute myeloid leukemia (R/R AML) with FLT3-ITD mutations.(NCT04842370) Study Design and Methods: PHI-101 was used in a range of once-daily (40-200 mg) regimens in a phase 1a, open label, dose-escalation expansion study in adult patients with R/R AML and in a phase 1b expansion study in adult patients with R/R FLT3 mutant AML. Study objectives were to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D), characterize the safety and tolerability and pharmacokinetic/pharmacodynamic profile, and assess the preliminary antitumor activity of PHI-101. A total of 30 pts with a median age of 64 years (range = 22-81) were enrolled in the phase 1a/1b clinical trials. Participants had received a mean of 3.9 prior therapies (range = 1-9). The most commonly observed mutations were FLT3-ITD mutations (70.0%), followed by both FLT3-ITD and FLT3-TKD mutations (13.3%). Most pts (72.0%) with known FLT3 mutations had previously received FLT3 inhibitors including gilteritinib (66.7%). Results: A total of 30 pts were enrolled in the two treatment arms of which 21 pts were evaluable, 9 pts in arm A (dose escalation) and 12 pts in arm B (dose expansion). Clinical responses with PHI-101 (composite complete remission [CRc; including complete remission (CR), complete remission with incomplete hematological recovery (CRi), an...