Phase 3 study of quizartinib (AC220) monotherapy vs salvage chemotherapy (SC) in patients (pts) with FLT3-ITD+ acute myeloid leukemia (AML) refractory to or relapsed (R/R) after 1st-line treatment with or without hematopoietic stem cell transplant (HSCT) consolidation: the QuANTUM-R study

Background

Approximately 25% of pts with AML have FLT3-internal tandem duplications (ITD) mutations, which are key oncogenic drivers of the disease. FLT3-ITD–positive AML is associated with poorer prognosis, decreased response to salvage therapy, increased risk of relapse, and shorter survival than FLT3-ITD–negative disease. Currently, there are no approved therapies targeting FLT3-ITD mutations, and improved therapeutic options are needed in this setting. Quizartinib is an oral, highly potent, and selective inhibitor that targets FLT3-ITD mutations. Previous studies of quizartinib monotherapy have reported composite complete response rates up to ≈ 46% in pts with R/R FLT3-ITD AML (Cortes JE, J Clin Oncol. 2013;31:3681-3687; Levis M, ASCO 2014 [abstract 7093]). Here, we describe QuANTUM-R, a multicenter, open-label, randomized phase 3 study (NCT02039726) to determine the efficacy of quizartinib in pts with FLT3-ITD–positive AML who are R/R within 6 months after first-line therapy.

Trial design

Eligible pts include adults aged ≥ 18 years with FLT3-ITD–positive AML in first relapse or refractory to prior therapy, with or without HSCT. Pts with prior exposure to quizartinib or other targeted FLT3-ITD inhibitors are excluded from this study. Approximately 326 pts will be randomized 2:1 to receive quizartinib or SC selected for each pt by the investigator prior to randomization. Options for SC regimens include mitoxantrone, etoposide, and intermediate-dose cytarabine (MEC); or fludarabine, cytarabine, and granulocyte colony stimulating factor with idarubicin (FLAG-IDA); or low-dose cytarabine (LoDAC). Quizartinib will be administered until lack of benefit or HSCT. The primary objective of this study is to determine whether quizartinib prolongs overall survival compared with SC in pts with R/R FLT3-ITD–positive AML. The secondary objective is to determine event-free survival with quizartinib vs SC. This study is currently recruiting pts.

Clinical trial identification

NCT02039726

Legal entity responsible for the study

Daiichi Sankyo, Inc.

Funding

Daiichi Sankyo, Inc.

Disclosure

J. Cortes: Consulting/Advisory Role with ARIAD, Ambit Pharmaceuticals, Astellas and Novartis. Research funding received from ARIAD, Ambit, Astells, Arog, Flexus and Novartis. G. Gammon: Employee of Daiichi Sankyo. S. Khaled: Honorarium, consulting/advisory role, speakers' bureau, travel, accommodations, expenses with Alexion; Research funding received from Ambit, MEI, Sanofi, Omeros. G. Martinelli: Consulting or Advisory Role with ARIAD, Amgen, Pfizer, and Roche; Speakers' Bureau with Novartis and BMS. A. Kramer: Honoraria received from Teva, Consulting/Advisory Role with NeoOncology, Research funding received from Bayer, Merck Serono, Travel, Accomodations, Expenses recieved from Teva. B. Steffen: Travel, accommodations, expenses received from Novartis, GSK, Astellas. D. Hogge: Consulting or advisory role with Sanofi; Travel, accommodations, expenses from Roche. B.A. Jonas: Consulting – Rigel Honorarium/Speaking – Celgene Research Funding – Pharmacyclics. H. Dombret: Honoraria received from Abmit and Daiichi Sankyo, Consulting/Advisory Role with Ambit and Daiichi Sankyo. A. Perl: Consulting fees recieved from, Daiichi Sankyo, Astellas Pharmaceuticals, Seattle Genetics, Asana Biosciences, and Actinium Pharmaceuticals.