QuANTUM-First study design

QuANTUM-First is the first pivotal trial to specifically study patients with FLT3-ITD+ AML from induction, through consolidation and maintenance^1,2

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

The primary efficacy measure was overall survival, defined as the time from randomisation until death from any cause.^1,2

QuANTUM-First STUDY DESIGN AND ENDPOINTS^2,3

Adapted from Erba, et al. 2023^2,3

Primary endpoint:
overall survival^1,2

Secondary endpoints:
EFS, CR and CRc²

Exploratory endpoints:
RFS and DoCR²

CRc is defined as complete remission or complete remission with incomplete neutrophil or platelet recovery.²

*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 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).^2,3 ‡Consolidation chemotherapy consisted of 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.^2,3

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.^1-3

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

VANFLYTA was studied in patients with newly diagnosed FLT3-ITD+ AML^1,2

Baseline patient characteristics²

Patient characteristics	VANFLYTA + standard chemotherapy* (N=268)	Placebo + standard chemotherapy* (N=271)

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

Discover more about VANFLYTA

VANFLYTA in addition to standard chemotherapy provided superior overall survival vs placebo + standard chemotherapy^1,2

REVIEW EFFICACY DATA

VANFLYTA demonstrated a generally manageable safety profile^1,2

REVIEW SAFETY DATA

VANFLYTA is a once-daily, oral, targeted treatment for FLT3-ITD+ AML¹

LEARN ABOUT VANFLYTA DOSING

Indication

VANFLYTA▼ (quizartinib) is indicated in combination with standard cytarabine and anthracycline induction and standard cytarabine consolidation chemotherapy, followed by VANFLYTA single-agent maintenance therapy for adult patients with newly diagnosed acute myeloid leukaemia (AML) that is FLT3-ITD positive.¹

Abbreviations

AML=acute myeloid leukaemia; CR=complete remission; CRc=composite complete remission; CYP3A4=cytochrome P450 3A4; DoCR=duration of complete remission; ECOG=Eastern Cooperative Oncology Group; EFS=event-free survival; FLT3=FMS (feline McDonough sarcoma)-like tyrosine kinase 3; HiDAC=high-dose cytarabine; HSCT=haematopoietic stem cell transplant; ITD=internal tandem duplication; ITT=intention-to-treat; NPM1=nucleophosmin 1; RFS=relapse-free survival; VAF=variant allelic frequency.

References

VANFLYTA Summary of Product Characteristics
Erba HP, Montesinos P, Kim HJ, et al. Quizartinib plus chemotherapy in newly diagnosed patients with FLT3-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023;401(10388):1571-1583.
Supplementary appendix to Erba HP, Montesinos P, Kim HJ, et al. Quizartinib plus chemotherapy in newly diagnosed patients with FLT3-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First): a randomised, double-blind, placebo-controlled, phase 3 trial (supplementary appendix). Lancet. 2023;401(10388):1571-1583.

QuANTUM-First study design

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QuANTUM-First is the first pivotal trial to specifically study patients with FLT3-ITD+ AML from induction, through consolidation and maintenance1,2

Baseline patient characteristics2

Discover more about VANFLYTA

VANFLYTA in addition to standard chemotherapy provided superior overall survival vs placebo + standard chemotherapy1,2

VANFLYTA demonstrated a generally manageable safety profile1,2

VANFLYTA is a once-daily, oral, targeted treatment for FLT3-ITD+ AML1