Results of a Phase 1/2a dose-escalation study of FF-10501-01, an IMPDH inhibitor, in patients with acute myeloid leukemia or myelodysplastic syndromes

被引：6

作者：

Garcia-Manero, Guillermo ^{[1
]}

Pemmaraju, Naveen ^{[1
]}

Alvarado, Yesid ^{[1
]}

Naqvi, Kiran ^{[1
]}

Ravandi, Farhad ^{[1
]}

Jabbour, Elias ^{[1
]}

De Lumpa, Ricardo ^{[1
]}

Kantarjian, Hagop ^{[1
]}

Advani, Anjali ^{[2
]}

Mukherjee, Sudipto ^{[2
]}

Gerds, Aaron ^{[2
]}

Carraway, Hetty E. ^{[2
]}

Nazha, Aziz ^{[2
]}

Iwamura, Hiroyuki ^{[3
]}

Murase, Motohiko ^{[3
]}

Bavisotto, Linda ^{[4
]}

Kurman, Michael ^{[4
]}

Maier, Gary ^{[4
]}

Johansen, Mary ^{[4
]}

Sekeres, Mikkael A. ^{[2
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA

[2] Cleveland Clin, Dept Hematol & Med Oncol, Leukemia Program, Cleveland, OH 44106 USA

[3] FUJIFILM Corp, Tokyo, Japan

[4] FUJIFILM Pharmaceut USA Inc, Cambridge, MA USA

来源：

LEUKEMIA & LYMPHOMA | 2020年 / 61卷 / 08期

关键词：

AML; MDS; CMML; IMPDH inhibition; Phase; 1; 2a; INTERNATIONAL WORKING GROUP; INOSINE-5'-MONOPHOSPHATE DEHYDROGENASE; RESPONSE CRITERIA; SCORING SYSTEM; OUTCOMES;

D O I：

10.1080/10428194.2020.1747065

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

FF-10501-01 potently inhibits inosine-5-monophosphate dehydrogenase (IMPDH), inducing anti-proliferative and pro-apoptotic effects in acute myeloid leukemia (AML) human cell lines resistant to hypomethylating agents. In this Phase 1/2a study, Phase 1 enrolled 38 patients with relapsed/refractory AML (n = 28) or myelodysplastic syndromes (MDS/CMML, n = 10) to receive FF-10501 oral doses 50-500 mg/m(2) BID for 14 or 21 days out of each 28-day cycle. Fifteen additional patients with HMA-resistant MDS/CMML (Phase 2a) were treated at 400 mg/m(2) BID for 21 days. Most Phase 1 adverse events were disease-related and low-grade. 3 of 19 (16%) evaluable AML patients achieved partial remission (31, 7, and 5 months). 2 of 20 (10%) evaluable MDS/CMML patients (Phase 1 and 2a) attained marrow complete remission, one continuing treatment for 17 months. While FF-10501-01 demonstrated clinical activity and target inhibition in heavily pretreated patients with AML and MDS/CMML, increased mucositis events led to Phase 2a closure (ClinTrials.gov#NCT02193958).

引用

页码：1943 / 1953

页数：11

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