UPDATED RESULTS FROM A PHASE 1 STUDY OF GILTERITINIB IN COMBINATION WITH
INDUCTION AND CONSOLIDATION CHEMOTHERAPY IN PATIENTS WITH NEWLY
DIAGNOSED AML
Keith W. Pratz1, Mohamad Cherry2, Jessica K. Altman3, Brenda W. Cooper4, Jose Carlos Cruz5, Joseph
G. Jurcic6, Mark J. Levis1, Tara L. Lin7, Alexander E. Perl8, Nikolai A. Podoltsev9, Gary J. Schiller10,
Chaofeng Liu11 and Erkut Bahceci11
(1)Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD
(2)Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK
(3)Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of
Medicine, Chicago, IL
(4)University Hospitals, Cleveland Medical Center, Cleveland, OH
(5)Methodist Physician Practices, San Antonio, TX
(6)Columbia University Medical Center, New York, NY
(7)University of Kansas Medical Center, Kansas City, KS
(8)Abramson Comprehensive Cancer Center, University of Pennsylvania, Philadelphia, PA
(9)Yale School of Medicine, New Haven, CT
(10)David Geffen School of Medicine at UCLA, Los Angeles, CA
(11)Astellas Pharma US, Inc., Northbrook, IL
Objective: As a single agent, the FLT3 inhibitor, gilteritinib, is efficacious in patients with FLT3-
mutated (FLT3mut+) relapsed/refractory AML. We evaluated once-daily oral gilteritinib combined with
front-line chemotherapy in patients with newly diagnosed (ND) AML.
Methods: This ongoing open-label, phase 1 study (NCT02236013) assesses the safety/tolerability and
antitumor effects of gilteritinib combined with 7+3 induction and high-dose cytarabine consolidation
chemotherapy, and as single-agent maintenance therapy, in adults with ND AML. During dose
escalation, successive cohorts of 3-6 patients received 40, 80, 120, or 200 mg/day of gilteritinib (Days
4-17 Schedule 1) and ≤2 cycles of induction (cytarabine 100 mg/m2/day, Days 1-7; idarubicin 12
mg/m2/day, Days 1-3). During dose expansion, patients received the recommended expansion dose
of gilteritinib (Schedule 1) combined with 7+3 idarubicin induction. Two additional cohorts received
gilteritinib on Days 8-21 (Schedule 2) with idarubicin (n=6; 12 mg/m2/day) or daunorubicin (n=5; 90
mg/m2/day) on Days 1-3. During consolidation, patients received cytarabine (1.5 g/m2 every 12
hours, Days 1, 3, and 5) and gilteritinib (Days 1-14) at the induction dose for ≤3 cycles. After
consolidation or transplantation, patients received gilteritinib (40, 80, or 120 mg/day) maintenance
therapy.
Results: Of 68 patients enrolled as of October 8, 2018 (safety analysis set, n=66), most were male
(63.6%; median age, 59.5 years range, 23-77); 36 (54.5%) were FLT3mut+ (FLT3-ITD, n=25; FLT3-TKD
D835, n=7; FLT3-ITD and -TKD D835, n=1; other FLT3 mutation, n=3). Two patients in the 200-mg/day
cohort experienced dose-limiting toxicities (neutropenia, neutropenic enterocolitis). The maximum
tolerated dose and the recommended expansion dose were established at 120 mg/day. Common
grade ≥3 adverse events (AEs) were febrile neutropenia (63.6%), thrombocytopenia (19.7%),
neutropenia (19.7%), decreased white blood cell count (19.7%), decreased platelet count (19.7%),
and decreased neutrophil count (16.7%). Serious drug-related AEs in >1 patient were febrile
neutropenia (n=11), sepsis (n=4), small intestinal obstruction (n=2), and decreased ejection fraction
(n=2). End-of-treatment investigator-reported composite complete remission (CRc) rate for
evaluable FLT3mut+ patients receiving gilteritinib on Schedule 1 (n=22) was 100%; the complete
remission (CR) rate was 72.7%. The CRc rate in FLT3mut+ patients receiving Schedule 2 induction with
SCIENTIFIC
PROGRAMME
RARE SUBSETS OF
ACUTE LEUKAEMIA
TRACKING LEUKAEMIC
STEM CELLS (LSCs)
ROUTINE DIAGNOSIS
GENE EXPRESSION
AND MUTATIONAL
PROFILING
DEBATE 1 – ALL
PATIENTS WITH
INTERMEDIATE-RISK
AML MUST BE
TRANSPLANTED
INTERACTIVE
CASES 1 – MUTATION-BASED
THERAPY
OFF-LABEL
ROUNDTABLE –
SHOULD WE REALLY
USE NEW TARGETED
INHIBITORS AS SINGLE
AGENTS ?
ADDITION OF A 3RD
AGENT TO FRONTLINE
7+3
ROUNDTABLE –
CURATIVE OPTIONS
FOR OLDER AML
INTERACTIVE CASES 2
DEBATE 2 - BEST
TREATMENT FOR
NPM1-MUTATED AML IN
THE NEXT FUTURE ?
ALLOGENEIC
HAEMATOPOIETIC
STEM CELL
TRANSPLANTATION
(HSCT)
IMMUNOTHERAPY FOR
ACUTE LEUKAEMIA
DEBATE 3 - T-ALL:
WHERE ARE WE GOING
NOW?
SELECTED ABSTRACTS
AND CLINICAL
CASES FOR AN ORAL
PRESENTATION
SELECTED ABSTRACTS
FOR A POSTER
PRESENTATION
DISCLOSURES