1040TiP - QuANTUM-First: phase 3, double-blind, placebo-controlled study of quizartinib in combination with induction and consolidation chemotherapy, and as...

Date 09 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Cancer in Adolescents
Leukaemia
Haematologic Malignancies
Presenter Richard Schlenk
Citation Annals of Oncology (2017) 28 (suppl_5): v355-v371. 10.1093/annonc/mdx373
Authors R. Schlenk1, H. Dombret2, S. Amadori3, P. Montesinos4, M. Levis5, M.A. Sekeres6, J. Cortes7, A. Perl8, O. Zernovak9, D. Mires10, N. Ge11, H. Zhang12, J. Hanyok13, S. Macintyre11, S. Gökmen11, K. Kobayashi14, H. Erba15
  • 1Trial Center, National Center for Tumor Diseases, 130/3 - Heidelberg/DE
  • 2Blood Disease Department, University Hospital Saint-Louis, 75475 Paris Cedex 10 - Paris/FR
  • 3Hematology, Tor Vergata University Hospital, P.I. 02133971008 - C.F. 80213750583 - Rome/IT
  • 4Hematology Department, Hospital Universitario La Fe, CP 46026 - Valenica/ES
  • 5Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, 21287 - Baltimore/US
  • 6Cleveland Clinic Taussig Cancer Institute, Cleveland Clinic, 44195 - Cleveland/US
  • 7Department Of Leukemia, MD Anderson Cancer Center, 77090 - Houston/US
  • 8Division Of Hematology/oncology, University of Pennsylvania, 19104 - Philadelphia/US
  • 9Clinical Development Oncology, Daiichi Sankyo, Inc., 08837 - Edison/US
  • 10Global Oncology R&d, Daiichi Sankyo, Inc., 08837 - Edison/US
  • 11Pharmacology Development, Daiichi Sankyo, Inc., 08837 - Edison/US
  • 12R&d Biostatistics & Data Management, Daiichi Sankyo, Inc., 08837 - Edison/US
  • 13Clinical Development, Daiichi Sankyo, Inc., 08837 - Edison/US
  • 14Clinical Development-oncology, R&d, Global Oncology R&d, Daiichi Sankyo, Inc., 08837 - Edison/US
  • 15Division Of Hematology/oncology, University of Alabama at Birmingham, 35294 - Birmingham/US

Abstract

Background

FLT3-internal tandem duplication (ITD) mutations occur in ∼25% of NDx AML pts and are associated with shorter response duration to standard chemotherapy (SC), higher relapse rate, and lower overall survival (OS) vs non–FLT3-ITD AML. Unlike the multi-kinase inhibitor, midostaurin, Quizartinib (Q), an oral, highly potent FLT3 inhibitor, has greater selectivity for FLT3. Early clinical studies of Q combined with SC demonstrated high clinical activity in NDx FLT3-ITD AML pts. This is an ongoing phase 3 trial of Q vs placebo (P) added to induction (IND) and consolidation (CON) chemotherapy and as maintenance therapy in NDx FLT3-ITD AML pts.

Trial design

Pts age 18-75 years with NDx FLT3-ITD AML and ECOG PS 0-2 are eligible. Key exclusion criteria: any prior treatment (including Q or any FLT3 inhibitors), investigational drug or device ≤30 days (d), immunotherapy ≤2 weeks, history of central nervous system leukemia, significant cardiovascular disease, QTcF >450 msec, active liver disease. Pts are randomized 1:1 to Q 40 mg (equivalent to 35.4 mg free base) or P administered with IND and CON chemotherapy (≤4 cycles high-dose cytarabine ± hematopoietic stem cell transplant) then as maintenance (Q 30 mg titrated to 60 mg, ≤12 28-d cycles; or P). In IND cycle 1, pts receive cytarabine 100 (or 200 mg/m2/d per updated protocol) for 7 d + anthracycline (daunorubicin 60 mg/m2/d or idarubicin 12 mg/m2/d) on days 1-3 (7 + 3). Starting day 8 of each IND and day 6 of each CON cycle, pts receive 14 d of daily Q 40 mg or P. On the second IND cycle, pts receive the 7 + 3 protocol, or investigators may substitute 5 + 2 d of cytarabine and anthracycline, per institutional standards, with Q or P starting on day 8 or day 6, respectively. The primary endpoint is event-free survival based on centrally adjudicated response assessment using local morphology results. Secondary endpoints are OS, CR, CRc (CR + CRi per latest IWG definitions). Enrollment is underway at 167 sites with a target enrollment of 536 pts at 275 sites worldwide.

Clinical trial identification

NCT02668653 First Received/Release date: January 22, 2016

Legal entity responsible for the study

Daiichi Sankyo, Inc.

Funding

Daiichi Sankyo, Inc.

Disclosure

R. Schlenk: Reports grants and personal fees from Novartis, grants from Amgen, grants and personal fees from Pfizer, grants from AstraZenca, grants from PharmaMar. H. Dombret: Grants and personal fees- Pfizer, Incyte, Jazz Pharma, Kite Pharma, Amgen; personal fees- Novartis, Celgene, Agios, Sunesis, Daiichi Sankyo, Karyopharm, Menarini, Astellas, Janssen, Servier, Seattle Genetics, Cellectis. S. Amadori: Reports personal fees from Novartis, personal fees from Amgen, personal fees from Celgene. P. Montesinos: Reports research funding: Pfizer, Celgene and advisory board: Daiichi Sankyo, Novartis, Pfizer, Celgene. M. Levis: Reports personal fees from Daiichi-Sankyo. M.A. Sekeres: Celgene and Millennium, advisory Boards, and steering committee for Daichii-Sankyo. J. Cortes: Grants and personal fees from Ambit/Daiichi, during the conduct of the study; grants and personal fees from Astellas, grants and personal fees from Ariad, grants from Arog, grants and personal fees from Novartis. A. Perl: personal fees and non-financial support- Daiichi Sankyo, Novartis, Arog Pharmaceuticals, personal fees from Pfizer, Astellas, Asana biosciences. O. Zernovak, S. Macintyre, S. Gökmen, K. Kobayashi, D. Mires, H. Zhang, J. Hanyok, N. Ge: Employee of Daiichi Sankyo, Inc. H. Erba: Personal fees- Celgene, Incyte, Novartis, Amgen, Jazz, Daiichi, ImmunoGen, Millennium/Takeda, Ono, Pfizer, Seattle Gen, Sunesis, Glycomimetics; grants- Agios, Amgen, Astellas, grants-Celator, Daiichi, ImmunoGen, Janssen, Juno, Millennium/Takeda, Seattle Gen