Vanflyta (quizartinib) / Daiichi Sankyo - LARVOL DELTA

Evaluation of Two Dose Levels of Quizartinib as Maintenance in FLT3-ITD (+) Acute Myeloid Leukemia Patients in Complete Remission (clinicaltrials.gov) - P2 | N=130 | Recruiting | Sponsor: Daiichi Sankyo | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

QuANTUM-First: Clinical Validation of the LeukoStrat Companion Diagnostic for the Selection of Patients With Acute Myeloid Leukemia Harboring FMS-Like Tyrosine Kinase 3-Internal Tandem Duplications for Treatment With Quizartinib. (PubMed, Arch Pathol Lab Med) - P3 | "The OS benefit provided by quizartinib in the ITT CDx+ population in the bridging study, with a median OS of 29.4 months for quizartinib versus 14.8 months for placebo (hazard ratio, 0.794; 2-sided stratified log-rank P = .06), was comparable with the OS benefit in the QuANTUM-First ITT. The LeukoStrat CDx FLT3 Mutation Assay aids in selecting newly diagnosed patients with FLT3 internal tandem duplication-positive AML for quizartinib therapy."

Companion diagnostic • Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • FLT3

QUIWI: Trial to Compare Efficacy and Safety of Chemotherapy/Quizartinib vs Chemotherapy/Placebo in Adults FMS-like Tyrosine Kinase 3 (FLT3) Wild-type Acute Myeloid Leukemia (AML) (clinicaltrials.gov) - P2 | N=273 | Completed | Sponsor: PETHEMA Foundation | Active, not recruiting ➔ Completed | Trial completion date: Sep 2024 ➔ Jan 2025

Trial completion • Trial completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Evolving Paradigms in AML: How Transplantation Fits in the Modern Therapeutic Landscape (ICBMT 2025) - "These include FLT3 inhibitors (midostaurin, gilteritinib, quizarti nib), IDH1/2 inhibitors (ivosidenib, enasidenib, olutasidenib), the BCL -2 inhibitor venetoclax, and oral hypomethylating agents, liposomal cytarabine , and targeted antibodies...In parallel, the CLIA -VEN regimen (cladribine, idarubicin, cytarabine, and venetoclax) has demonstrated high efficacy in younger AML patients, with CRc rates exceeding 90%, MRD negativity in 89%, and a 5 -year OS of 73% —even among high -risk subgroups such a s those with ELN adverse risk and KMT2A mutations (Bouligny et al...In a recent phase I/II study, the triplet combination of decitabine, venetoclax, and quizartinib in older patients with FLT3 -ITD AML resulted in 92% CRc, with 67 –71% The International Congress of BMT 202 5 September 11(Thu) – 13(Sat), 2025; BEXCO, Busan 2 / 2 achieving flow or molecular negativity (Yilmaz et al...Maximizing MRD negativity before transplant, integrating novel agents upfront, and o..."

Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Transplantation • FLT3 • IDH1 • IDH2 • KMT2A • NPM1

Triplet Therapy With Decitabine, Venetoclax, and Quizartinib for FLT3-ITD Mutated AML: A Phase 1/ 2 Study (SOHO 2025) - "Context: Newly diagnosed patients with FLT3-ITD mutated (FLT3m) acute myeloid leukemia (AML) who are ineligible for intensive induction chemotherapy experience poor outcomes with median overall survival (OS) <1 year with azacitidine+venetoclax...Forty-seven R/R AML patients were heavily pretreated (median 3 [1-5] prior therapies), 85% (39/46) had received ≥1 prior FLT3 inhibitors—with 76% having prior exposure to gilteritinib and 37% having undergone prior ASCT... Decitabine+venetoclax+quizartinib combination showed remarkable responses in the frontline setting; 94% achieved CRc, with median ANC and platelet recovery of 37 and 36 days, respectively. Median OS was not reached."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3

Dose Escalation and Expansion of Ziftomenib in Combination With Quizartinib in Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=44 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

A Study to Evaluate QTc Prolongation With Quizartinib in Healthy Subjects Under Rapid Acceleration of Heart Rate (clinicaltrials.gov) - P1 | N=70 | Completed | Sponsor: Daiichi Sankyo | Recruiting ➔ Completed | Trial completion date: Oct 2025 ➔ Jun 2025 | Trial primary completion date: Oct 2025 ➔ Jun 2025

Trial completion • Trial completion date • Trial primary completion date

How to Best Incorporate FLT3 Inhibitors in the Management of FLT3 Mutated AML (SOHO 2025) - "Studies randomizing FLT3 inhibitors plus venetoclax and azacitidine vs venetoclax and azacitidine alone are also ongoing...Although no randomized quizartinib vs midostaurin studies are available or expected, results from randomized studies comparing gilteritinib to midostaurin added to cytarabine/daunorubicin-based intensive chemotherapy recently were presented in abstract form...Preclinical data have already suggested a substantial synergy of this approach. Data from ongoing trials combining will emerge soon and are eagerly awaited."

Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Acute Promyelocytic Leukemia • Oncology • ABL1 • BCR • DNMT3A • FLT3 • NPM1

Screening for Antileukemia Agents in FMS-like Tyrosine Kinase 3 (FLT3)-Mutated Acute Myeloid Leukemia Cells. (PubMed, ACS Pharmacol Transl Sci) - "Furthermore, combining HI042 with the FLT3 inhibitor quizartinib synergistically enhanced apoptosis and reduced cell proliferation. These findings highlight HI042's dual activity in inducing differentiation and apoptosis while synergizing with established therapies. Overall, HI042 emerges as a promising candidate for targeted therapies against FLT3-ITD-mutated AML, addressing a critical need for novel treatment strategies for this high-risk AML subgroup."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • FLT3 • ITGAM

Updates on Therapy Options in Fit and Unfit Patients with Newly Diagnosed AML. (PubMed, Curr Treat Options Oncol) - "In our practice, we continue to use 7 + 3 induction for fit patients, adding midostaurin or quizartinib for FLT3-mutated AML, or gemtuzumab ozogamicin for core binding factor (CBF) AML expressing CD33...In the presence of IDH1 mutations, we consider azacitidine combined with ivosidenib. If venetoclax is contraindicated or not tolerated, targeted therapies such as gilteritinib, ivosidenib, or enasidenib may be appropriate based on mutation profile...When feasible, clinical trial enrollment should be considered for newly diagnosed patients with these alterations. As the therapeutic landscape for AML continues to evolve, timely molecular characterization is more essential than ever to optimize outcomes and select the most appropriate frontline strategy."

Journal • Review • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CD33 • FLT3 • IDH1 • IDH2 • KMT2A • NPM1

Validation of pharmacokinetic model for quizartinib quantified by UPLC-MS/MS in patients with FLT3-ITD negative newly diagnosed acute myeloid leukemia. (PubMed, Eur J Clin Pharmacol) - P2 | "This study presents a replicable UPLC-MS/MS method for the determination of quizartinib in plasma. The validated popPK model can be used to optimize dosing strategies in future clinical studies."

Journal • PK/PD data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

QuANTUM-Wild: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial of Quizartinib in Combination With Chemotherapy and as Single-Agent Maintenance in FLT3-ITD-Negative Acute Myeloid Leukemia (AML) (SOHO 2025) - P3 | "Treatment includes standard induction with cytarabine and an anthracycline plus Quiz/placebo, followed by up to 4 cycles of consolidation (±allogeneic hematopoietic stem cell transplant) with high-dose cytarabine and Quiz/placebo, and then single-agent maintenance with Quiz/placebo in 28-day cycles for up to 36 cycles."

Clinical • Combination therapy • P3 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • NPM1

“The Canada’s Drug Agency pan-Canadian Oncology Drug Review Expert Review Committee recommends that quizartinib be reimbursed in combination with standard cytarabine and anthracycline induction and standard cytarabine consolidation chemotherapy, followed by quizartinib maintenance monotherapy, for the treatment of adult patients with newly diagnosed acute myeloid leukemia…are met.” (Ottawa (ON): Canadian Agency for Drugs and Technologies in Health)

Reimbursement • Acute Myelogenous Leukemia • Hematological Malignancies • Oncology

Rational combination of homoharringtonine to selectively target FLT3-ITD acute myeloid leukemia through synthetic lethality. (PubMed, Phytomedicine) - "FLT3-ITD AML cells represent a responsive subgroup to HHT treatment in vitro and in vivo. The combination of HHT and quizartinib demonstrates optimal efficacy and selectivity against FLT3-ITD AML cells in xenografts, with no observed toxicity."

IO biomarker • Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BAX • FLT3 • MCL1

Sitravatinib combined with venetoclax exerts effective synergy to eliminate acute myeloid leukemia cells with FLT3-ITD mutations. (PubMed, Transl Oncol) - "The combination of venetoclax and FLT3 inhibitors gilteritinib and quizartinib has shown promising results in reducing leukemia burden and improving survival in pre-clinical studies and clinical trials of AML with FLT3 mutation. Finally, we tested the potential application of sitravatinib plus venetoclax in vivo using patient-derived xenografts, and found that the combined therapy was significantly more effective in inhibiting leukemia cell expansion, reducing infiltration in the spleen, and prolonging survival time compared to a single administration. Our study demonstrates the potential use of sitravatinib plus venetoclax as an alternative therapeutic strategy to treat AML patients with FLT3-ITD mutation."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2L1 • FLT3 • MCL1

Histamine dihydrochloride and low-dose interleukin-2 in an emerging landscape of relapse prevention in acute myeloid leukemia. (PubMed, Ther Adv Hematol) - "More recent trials have identified efficacious remission maintenance strategies, including (1) midostaurin or quizartinib for patients with FLT3-mutated AML, (2) oral azacitidine for older AML patients, and (3) immunotherapy with histamine dihydrochloride and low-dose interleukin-2 (HDC/IL-2) for younger patients. We discuss clinical efficacy in relation to patient age and anti-leukemic immunity as well as leukemic cell chemosensitivity, chromosomal integrity, and mutational profiles. Finally, we propose a role for HDC/IL-2 within an evolving landscape of strategies to achieve durable remission in a broader population of AML patients."

IO biomarker • Journal • Review • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3

TARGETING FLT3 IN B-ALL: FROM GENOMIC INSIGHTS TO THERAPEUTIC APPLICATIONS (EHA 2025) - "In vitro studies using 6 FLT3i [Gilteritinib (Gil), Midostaurin, Crenolanib, Sorafenib, Quizartibin and Ponatinib (Pon)] and Venetoclax (Ven) were conducted on pt primary cells and on 11 B-ALL wt and 4 AML cell lines (OCI-AML3 wt; MV-4-11, MOLM-13, MONO-MAC6 FLT3-mut).Data analyses highlight the heterogeneity in FLT3i sensitivity across pediatric ALL cell lines with midostaurin, Pon and quizartinib were among the top scoring drugs for most cell lines (Fig. FLT3 alterations identify a novel subgroup of TN B-ALL with therapeutic potential also in combination regimens."

Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia • ABL1 • FLT3 • IKZF1 • KMT2A • NUP214 • ZNF384

PHASE I/II STUDY OF DECITABINE, VENETOCLAX, AND QUIZARTINIB TRIPLET COMBINATION IN FLT3-ITD MUTATED AML (EHA 2025) - "Background: Patients (pts) newly diagnosed with FLT3-ITD mutated (m) acute myeloid leukemia (AML) who are ineligible for intensive induction chemotherapy (IC) experience poor outcomes with a median overall survival (OS) of 9.9 months with azacitidine+venetoclax (VEN) (Konopleva et al...With a median follow-up of 17 months, the median OS was not reached.(Figure 1).The 47 R/R AML pts were heavily pretreated (median 3 [range 1-5] prior AML therapies); 85% (40/47) had received ≥1 prior FLT3 inhibitors (FLT3i's), with 78% having prior exposure to gilteritinib and 38% having undergone prior ASCT... The combination of decitabine, venetoclax, and quizartinib demonstrated significant results in the frontline setting; 92% of pts achieved CRc with median platelet and ANC recovery of 36 and 37 days, and median OS not reached. The study continues to accrue, and updated results will be reported at the meeting."

P1/2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Infectious Disease • Neutropenia • Pneumonia • Respiratory Diseases • Septic Shock • FLT3

MULTIDRUG RESISTANCE AND METABOLIC REPROGRAMMING IN FLT3 MUTANT AML FOLLOWING PROLONGED FLT3 INHIBITOR TREATMENT (EHA 2025) - "MV4-11QR cells also showed cross-resistance to other FLT3i, including midostaurin (IC50 wt: 38.1 nM vs. QR: not reached [NR]) and gilteritinib (IC50 wt: 2.8 nM vs. QR: 65.6 nM). Given their broad resistance profile, we further investigated resistance to other AML therapies, such as venetoclax (VEN) and cytarabine (AraC)... Our findings provide evidence of cellular reprogramming following prolonged AC220 exposure. Investigating the mechanisms underlying FLT3i resistance may guide the development of combination therapies to overcome this challenge."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ACOX1 • FLT3 • PTPN1 • SOD2 • TP53

SORAFENIB REVERSES VENETOCLAX SECONDARY RESISTANCE IN ACUTE MYELOID LEUKAEMIA VIA DOWNREGULATION OF THE RAS-RAF-MEK-ERK SIGNALLING PATHWAY (EHA 2025) - "Peripheral leukemic cells were analysed via flow cytometry, haematological parameters were monitored through blood counts, and spleen size was measured post-treatment.High-throughput in vitro drug sensitivity screening identified six venetoclax-synergistic agents from thirty-one candidates: ruxolitinib, sorafenib, A1331852, mivebresib, quizartinib, and nilotinib. Sorafenib reverses secondary venetoclax resistance in AML by inhibiting the Ras-Raf-MEK-ERK pathway and downregulating anti-apoptotic proteins (BCL-2, MCL-1, BCL-XL), thereby synergising with venetoclax to inhibit resistant leukaemic cells. This study provides a promising therapeutic strategy for overcoming venetoclax resistance in AML."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2 • BCL2L1 • MCL1

VANFLYTA is Now Approved in Canada Specifically for Adult Patients with Newly Diagnosed FLT3-ITD Positive AML (Canada Newswire) - "Daiichi Sankyo's...VANFLYTA (quizartinib) has been approved by Health Canada for use in combination with standard cytarabine and anthracycline induction and standard cytarabine consolidation chemotherapy, followed by VANFLYTA maintenance monotherapy, for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) that is FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) positive....A validated test is required to confirm the FLT3-ITD status of AML....The approval of VANFLYTA by Health Canada was based on the results of the QuANTUM-First phase 3 clinical trial."

Canada approval • Evidence highlight • Acute Myelogenous Leukemia • FLT3

THE COMBINATION OF A FLT3-ITD, NPM1MUT AND AN EPIGENETIC REGULATORY GENE MUTATION CONFERS UNIQUE SENSITIVITY TO QUIZARTINIB: ANALYSIS FROM THE QUANTUM-FIRST TRIAL (EHA 2025) - P3 | "In pts with FLT3-ITD+ ND AML, an NPM1mut co-mutation appears to confer an additional survival benefit for those receiving Quiz. The triple-mutation of FLT3-ITD, NPM1, and an epigenetic regulatory gene, showed particular susceptibility to Quiz treatment, regardless of age, with the greatest benefit observed in pts with FLT3-ITD, NPM1mut, and DNMT3Amut. This suggests that the clinical efficacy of FLT3 inhibitors is influenced by other co-mutations, and that this triple-mutation signature represents a sub-entity of AML that is particularly sensitive to Quiz FLT3 inhibition."

Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • DNMT3A • FLT3 • IDH1 • IDH2 • NPM1 • TET2 • WT1

MEASURABLE MINIMAL RESIDUAL DISEASE BY AN ULTRA-SENSITIVE NGS METHOD TO EVALUATE THE RESPONSE IN ACUTE MYELOID LEUKEMIA, THE VENAQUI CLINICAL TRIAL (EHA 2025) - "Venetoclax (VEN) with hypomethylating agents (HMA) or Low doses ara-C (LDAC) combination is standard for unfit AML patients...Aims: This study is aimed to explore the use of CloneSight NGS-MRD utility in predicting outcomes within the VENAQUI Phase 1-2 trial (VEN-AZA/LDAC + Quizartinib; EUDRACT2020-000406-28)... The MRD NGS study using an ultrasensitive assay showed that the triplet used in this clinical trial could lead to deep responses, even after cycle 1. The persistence of MRD-positive at cycle 4 predicted worse OS and RFS across all compartments (BM, cfDNA, CTC). Understanding molecular dynamics post-targeted therapy may improve AML outcomes."

Clinical • Minimal residual disease • Next-generation sequencing • Residual disease • Acute Myelogenous Leukemia • Geriatric Disorders • Hematological Malignancies • Leukemia • Oncology

QUANTUM-WILD: A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF QUIZARTINIB IN COMBINATION WITH CHEMOTHERAPY AND AS SINGLE-AGENT MAINTENANCE IN FLT3-ITD-NEGATIVE ACUTE MYELOID LEUKEMIA (AML) (EHA 2025) - P3 | "Treatment includes standard induction with cytarabine and an anthracycline plus Quiz/Pbo, followed by up to 4 cycles of consolidation (+/– allo-HSCT) with high-dose cytarabine and Quiz/Pbo, and then single-agent maintenance with Quiz/Pbo in 28d cycles for up to 36 cycles (Fig.). Reused with permission. This abstract was accepted and previously presented at the 2025 ASCO Annual Meeting."

Clinical • Combination therapy • P3 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • FLT3 • NPM1

FINAL RESULTS OF VEN A QUI TRIAL: A PHASE I-II TRIAL COMPARING VENETOCLAX WITH LOW DOSE CYTARABINE OR AZACITIDINE COMBINED WITH QUIZATINIB IN NON-FIT PATIENTS WITH ACUTE MYELOID LEUKEMIA (EHA 2025) - "Background: Quizartinib could improve complete remission (CR) and overall survival (OS) in AML patients treated with Venetoclax and LDAC or Aza combination. We established a R2PD of Quirzatinib and Venetoclax with LDAC/Aza. No differences in cCR and OS was found between LDAC and Aza. Patients with de novo AML, FLT3-ITD, NPM1 and IDH2 seems to achieve outstanding cCR and median OS."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Infectious Disease • Neutropenia • Septic Shock • Thrombocytopenia • FLT3 • IDH1 • IDH2 • NPM1 • RUNX1 • SRSF2 • TET2 • TP53