QuANTUM-First study design
QuANTUM-First is the first pivotal trial to specifically study FLT3-ITD+ AML patients over a 5-year period from induction, through consolidation and maintenance1-4
The efficacy and safety of VANFLYTA(quizartinib) were studied in QuANTUM-First – a Phase 3, randomised, double-blind, placebo-controlled, multicentre, global study of 539 adult patients between 18 and 75 years of age, with newly diagnosed FLT3-ITD+ AML. Patients were randomised to placebo (n=271) or VANFLYTA (n=268).1,2
QuANTUM-First STUDY DESIGN AND ENDPOINTS2,5
Adapted from Erba, et al. 20232
CRc is defined as complete remission or complete remission with incomplete neutrophil or platelet recovery.2
overall survival1
EFS, CR and CRc2
RFS and DoCR2
*Patients were stratified by age (<60 vs ≥60 years), white blood cell count at diagnosis (<40×109/L vs ≥40×109/L) and region (North America, Europe vs Asia, other regions).2
**Patients received salt-form VANFLYTA 40 mg orally once daily on Days 8–21 of 7+3 (cytarabine [100 or 200 mg/m2/day] on Days 1–7 plus daunorubicin [60 mg/m2/day] or idarubicin [12 mg/m2/day] on Days 1–3), and on Days 8–21 or 6–19 of an optional second induction (7+3 or 5+2 [5 days cytarabine plus 2 days daunorubicin or idarubicin], respectively).2,5
†Consolidation chemotherapy consisted of salt-form VANFLYTA 40 mg orally once daily on Days 6–19 of high-dose cytarabine (1.5 to 3 g/m2 every 12 hours on Days 1, 3 and 5) for up to 6 doses.2,5
Standard chemotherapy included cytarabine- and anthracycline-based induction and consolidation regimens (either daunorubicin or idarubicin). Eligible patients, including those who underwent allogeneic HSCT, continued with single-agent VANFLYTA or standard chemotherapy. There was no re-randomisation at the start of post-consolidation therapy.1,2,6
A second course of induction was administered to 21% of the patients; 65% initiated at least one cycle of consolidation; and 44% initiated maintenance treatment with VANFLYTA:2
- For patients concomitantly receiving a strong CYP3A4 inhibitor, the dose was reduced to 20 mg/day2
- 29% (157/539) of the patients underwent HSCT in first CR7
Baseline patient characteristics2
Patient characteristics | VANFLYTA + | Placebo + | |
|---|---|---|---|
Age, years | |||
Median (range) | 56 (23–75) | 56 (20–75) | |
≥60 years, % | 40 | 40 | |
Sex, % | |||
Male | 46 | 45 | |
Female | 54 | 55 | |
Race, % | |||
Asian | 30 | 29 | |
Black or African American | 1 | 2 | |
American Indian or Alaska Native | 0 | <1 | |
White | 59 | 60 | |
Other | 10 | 9 | |
ECOG performance status, % ** | |||
0 | 32 | 36 | |
1 | 50 | 50 | |
2 | 18 | 13 | |
Cytogenetic risks, %† | |||
Favourable | 5 | 7 | |
Intermediate | 74 | 71 | |
Unfavourable | 7 | 10 | |
Unknown | 14 | 11 | |
Missing | 0 | <1 | |
Adapted from Erba, et al. 20232
*Three patients in the ITT set were randomised but not treated in each arm.2
**One patient in the placebo group was missing an ECOG status.2
†Favourable: inv(16), t(16;16), t(8;21) or t(15;17); intermediate: normal, 8, 6 or −Y; unfavourable: deI(5q), −5, del(7q), −7 or complex karyotype.2
Of the 539 randomised patients:
- The majority of the patients (72%) had intermediate-risk cytogenetics at baseline2
- FLT3-ITD VAF was ≥3% to ≤25% in 36% of patients, >25% to ≤50% in 52% of patients, and >50% in 12% of patients2
- NPM1 mutations were identified in 52% of patients2