|
|
Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Medicine / Faculty of Medicine >
Peer-reviewed Journal Articles, etc >
Zandelisib (ME-401) in Japanese patients with relapsed or refractory indolent non-Hodgkin's lymphoma : an open-label, multicenter, dose-escalation phase 1 study
| Title: | Zandelisib (ME-401) in Japanese patients with relapsed or refractory indolent non-Hodgkin's lymphoma : an open-label, multicenter, dose-escalation phase 1 study |
| Authors: | Goto, Hideki Browse this author →KAKEN DB | | Izutsu, Koji Browse this author →KAKEN DB | | Ennishi, Daisuke Browse this author | | Mishima, Yuko Browse this author | | Makita, Shinichi Browse this author | | Kato, Koji Browse this author | | Hanaya, Miyoko Browse this author | | Hirano, Satoshi Browse this author | | Narushima, Kazuya Browse this author | | Teshima, Takanori Browse this author →KAKEN DB | | Nagai, Hirokazu Browse this author | | Ishizawa, Kenichi Browse this author |
| Keywords: | Dose escalation | | Follicular lymphoma | | Marginal zone lymphoma | | PI3K delta inhibitor | | Zandelisib |
| Issue Date: | 1-Dec-2022 |
| Publisher: | Springer |
| Journal Title: | International journal of hematology |
| Volume: | 116 |
| Issue: | 6 |
| Start Page: | 911 |
| End Page: | 921 |
| Publisher DOI: | 10.1007/s12185-022-03450-5 |
| Abstract: | The selective phosphatidylinositol 3-kinase delta inhibitor zandelisib demonstrated favorable safety and efficacy [objective response rate (ORR) 79%] in patients with B-cell malignancies in a phase 1b study in the US and Switzerland. In this phase 1 dose-escalation study (NCT03985189), 9 Japanese patients with relapsed/refractory indolent non-Hodgkin's lymphoma (R/R iNHL) received zandelisib on a continuous daily schedule (45 or 60 mg) until progressive disease/unacceptable toxicity. No dose-limiting toxicities were observed. The maximum tolerated dose was not reached. At a median follow-up of 17.5 months, Grade >= 3 treatment-emergent adverse events that occurred in 2 or more patients were neutrophil count decreased (55.6%; 5/9) and diarrhea (33.3%; 3/9) Immune-related toxicities, including hepatobiliary disorder, aspartate/alanine aminotransferase increased, diarrhea/colitis, organizing pneumonia, stomatitis, and rash, led to zandelisib discontinuation in 4 patients. The investigator-assessed ORR, based on modified Lugano criteria, was 100%, including 2 complete responses (22.2%; in follicular lymphoma patients receiving 60 mg/day). Median duration of response, progression-free survival, and time to response were 7.9, 11.1, and 1.9 months, respectively. Zandelisib demonstrated a manageable safety profile at 60 mg, the recommended phase 2 dose (RP2D) in Japanese patients. The RP2D resulted in favorable pharmacokinetics and anti-tumor efficacy in Japanese patients with R/R iNHL. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/88793 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
|
|
