XOSPATA Was Evaluated in a Pre-planned Interim Analysis of an Ongoing Phase 3 Trial1,2

  • The ADMIRAL trial is an ongoing Phase 3, open-label, multicenter, randomized clinical trial in adult patients with relapsed or refractory FLT3m+ AML1,2
  • The efficacy of XOSPATA was evaluated in a pre-planned interim analysis that included 138 patients randomized to the XOSPATA arm1,2
    • Efficacy was established on the basis of CR/CRh rate, DOR, and rate of conversion from transfusion dependence to transfusion independence1
    • OS data were not mature at the time of the pre-planned interim analysis3

ADMIRAL Study Design1-3

ADMIRAL Study Design ADMIRAL Study Design

*XOSPATA was given orally at a starting dose of 120 mg daily until unacceptable toxicity or lack of clinical benefit. Dose reductions were allowed to manage adverse events, and dose increases were allowed to increase clinical benefit.1

Eligibility Criteria3†

  • Adult patients with primary AML or AML secondary to MDS
  • No APL, BCR-ABL-positive leukemia, or AML secondary to chemotherapy for other neoplasms (except for MDS)
  • Positive for FLT3 mutations (FLT3-ITD, FLT3-TKD-D835, or FLT3-TKD-I836) as determined by the central lab
  • Refractory to, or relapsed after, first-line AML therapy (with or without HSCT)
  • Prior treatment with midostaurin or sorafenib was allowed
  • No clinically active central nervous system leukemia
  • Excluded patients with long QT syndrome at screening and patients with hypokalemia and hypomagnesemia at screening (defined as values below LLN)

Does not include all patient inclusion and exclusion criteria for the ADMIRAL trial.3

ABL=Abelson murine leukemia viral oncogene homolog 1; AML=acute myeloid leukemia; APL=acute promyelocytic leukemia; BCR=breakpoint cluster region; CR=complete remission; CRh=complete remission with partial hematologic recovery; DOR=duration of CR/CRh; FLT3=FMS-like tyrosine kinase 3; HSCT=hematopoietic stem cell transplant; ITD=internal tandem duplication; LLN=lower limit of normal; m+=mutation-positive; MDS=myelodysplastic syndrome; OS=overall survival; QT=cardiac ventricular repolarization; TKD=tyrosine kinase domain.

Characteristics of Patients Enrolled in the ADMIRAL Trial1

Baseline Patient Characteristics1 XOSPATA
120 mg daily
(N=138)
n (%)
Age (years) Median (range) 60 (20-84)
Sex Male 64 (46)
Female 74 (54)
FLT3 mutation status FLT3-ITD alone 121 (88)
FLT3-TKD alone 12 (9)
FLT3-ITD and FLT3-TKD 5 (4)
AML disease status Untreated relapse 82 (59)
Primary refractory 56 (41)
Baseline ECOG PS 0-1 113 (82)
≥2 25 (18)
Transfusion dependence
at baseline
Transfusion
dependent
106 (77)
Transfusion
independent
32 (23)
Prior transplant Prior stem cell
transplant
27 (20)

Patients were defined as transfusion dependent at baseline if they received any RBC or platelet transfusions within the 56-day baseline period.1

ECOG PS=Eastern Cooperative Oncology Group performance status; RBC=red blood cell.

Select Safety Information

Pancreatitis There have been rare reports of pancreatitis in patients receiving XOSPATA in clinical studies. Evaluate patients who develop signs and symptoms of pancreatitis. Interrupt and reduce the dose of XOSPATA in patients who develop pancreatitis.

ADMIRAL TRIAL

XOSPATA Achieved Clinically Meaningful CR/CRh Rates1

Rate of CR/CRh1

Rate of CR/CRh Rate of CR/CRh
  • The rate of CR/CRh was evaluated in a pre-planned interim analysis of patients randomized to the XOSPATA arm (N=138)1,2
  • Only responses prior to HSCT were included in the response rate1
  • Among patients with FLT3-ITD or FLT3-ITD-TKD mutations, the CR/CRh rate was 23.0% (n=29/126), and none of the 12 patients with FLT3-TKD only mutations achieved CR/CRh1
  • The median follow-up was 4.6 months (95% CI: 2.8, 15.8)1
  • CR was defined as normal marrow differential with <5% blasts, ANC ≥1.0 x 109/L and platelets ≥100 x 109/L, no evidence of extramedullary leukemia, and must have been RBC and platelet transfusion independent1
  • CRh was defined as marrow blasts <5%, partial hematologic recovery, ANC ≥0.5 x 109/L and platelets ≥50 x 109/L, no evidence of extramedullary leukemia, and could not have been classified as CR1

Median Duration of Remission1

  • 4.6 months
    median duration of CR/CRh
    (range: 0.1 to 15.8 months§; n=29/138)
  • 8.6 months
    median duration of CR
    (range: 1.0 to 13.8 months; n=16/138)
  • 2.9 months
    median duration of CRh
    (range: 0.1 to 15.8 months§; n=13/138)
  • At the time of the first interim DOR analysis, 14 patients were still in remission
  • DOR was defined as the time from the date of either first CR or CRh until the date of a documented relapse of any type, with deaths counted as events

Median Time to First Response1

Median Time to First Response Median Time to First Response

§Response was ongoing.1

XOSPATA Helped Nearly One-Third of Patients Achieve Transfusion Independence During Any 56-Day Post-Baseline Period1

Transfusion Independence Conversion Rate1

Among patients who were transfusion dependent at baseline (n=106)

Transfusion Independence Conversion Rate Transfusion Independence Conversion Rate
  • Of the 32 patients who were transfusion independent at baseline, more than half (53.1%) remained transfusion independent with XOSPATA during any 56-day post-baseline period (n=17/32)

XOSPATA may help patients with relapsed or refractory FLT3m+ AML1:
Achieve CR/CRh Extend mDOR Convert to transfusion independence

||Transfusion independence is defined as patients who were dependent on RBC and/or platelet transfusions at baseline and became independent of RBC and platelet transfusions during any 56-day post-baseline period.1

ANC=absolute neutrophil count; CI=confidence interval; mDOR=median duration of CR/CRh.

Select Safety Information

Embryo-Fetal Toxicity XOSPATA can cause embryo-fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with XOSPATA and for at least 6 months after the last dose of XOSPATA. Advise males with female partners of reproductive potential to use effective contraception during treatment with XOSPATA and for at least 4 months after the last dose of XOSPATA. Pregnant women, patients becoming pregnant while receiving XOSPATA or male patients with pregnant female partners should be apprised of the potential risk to the fetus.