Vanflyta (quizartinib) / Daiichi Sankyo, Innovent Biologics - LARVOL DELTA

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. (PubMed, Lancet) - P3 | "The addition of quizartinib to standard chemotherapy with or without allo-HCT, followed by continuation monotherapy for up to 3 years, resulted in improved overall survival in adults aged 18-75 years with FLT3-ITD-positive newly diagnosed AML. Based on the results from the QuANTUM-First trial, quizartinib provides a new, effective, and generally well tolerated treatment option for adult patients with FLT3-ITD-positive newly diagnosed AML."

Journal • P3 data • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Transplantation • FLT3

Atypical Bullous Sweet Syndrome. (PubMed, R I Med J (2013)) - "Sweet syndrome has also been rarely linked to FLT3 inhibitors such as quizartinib. We report a 71-year-old male with acute myeloid leukemia who developed bullous Sweet syndrome following concurrent exposure to pegfilgrastim and quizartinib."

Journal • Acute Myelogenous Leukemia • Dermatology • Hematological Malignancies • Leukemia • Oncology

PRELIMINARY RESULTS OF QUIWI: A DOUBLE BLINDED, RANDOMIZED CLINICAL TRIAL COMPARING STANDARD CHEMOTHERAPY PLUS QUIZARTINIB VERSUS PLACEBO IN ADULT PATIENTS WITH NEWLY DIAGNOSED FLT3-ITD WILD-TYPE AML (EHA 2023) - P2 | "The randomized SORAML trial from the SAL group, including FLT3-ITD mutated and WT, showed that the addition of type II inhibitor sorafenib improved leukemia-free, but not overall survival (OS) among newly diagnosed fit AML patients...The trial was conducted in two phases: an open-label safety run-in phase exploring Cytarabine 200 mg/m 2 (days 1-7), Idarubicin 12 mg/m 2 (days 1-3), and Quiz 60 mg/d x 14 days to establish the dose for the randomized phase... Our study suggests that the addition of Quiz to 3+7 may prolong OS in newly diagnosed FLT3-ITD WT AML. A large biomarker plan to clarify underlying molecular mechanisms and final analyses with longer follow-up will be reported by the end of 2023. flt3 inhibitor, Treatment, Clinical trial, Acute myeloid leukemia"

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • NPM1

Phase I/II Study of Quizartinib, Venetoclax, and Decitabine Triple Combination in FLT3-ITD Mutated AML (ASH 2023) - "These patients have a median overall survival (OS) of 9.9 months when treated with the standard of care regimen (azacitidine and venetoclax). The combination of DAC + VEN + Quiz demonstrated activity in heavily pretreated and prior FLT3i-exposed (including 78% with prior gilteritinib exposure) R/R FLT3-ITDm pts, with a CRc rate of 68% and a median OS of 7.1 months. In the frontline setting, all pts achieved CRc with no early mortality, median count recovery of 40 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 • Febrile Neutropenia • Gastrointestinal Disorder • Infectious Disease • Neutropenia • Pneumonia • Respiratory Diseases • Septic Shock • FLT3

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

Long-Term Survival Outcomes and Cytogenetic/Molecular Patterns of Relapse in Adults with FLT3-Mutated AML Receiving Frontline Triplet Therapy with a Hypomethylating Agent, Venetoclax and FLT3 Inhibitor (ASH 2024) - "The FLT3i used was gilteritinib in 61 pts (69%), quizartinib in 18 (21%), sorafenib in 7 (8%), and midostaurin in 2 (2%). A majority of relapses are driven entirely by FLT3 wild-type clones. RAS pathway mutations at diagnosis are associated with worse outcomes, and new RAS pathway mutations were observed in 20% of relapses."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BRAF • FLT3 • GATA2 • IKZF1 • KRAS • NF1 • NPM1 • NRAS • PTPN11 • RUNX1 • SF3B1 • TET2 • WT1 • ZRSR2

TRIPLET THERAPY WITH QUIZARTINIB, DECITABINE, AND VENETOCLAX IN NEWLY DIAGNOSED AND RELAPSED/REFRACTORY FLT3-ITD ACUTE MYELOID LEUKEMIA (EHA 2026) - "Background Venetoclax (VEN) combined with hypomethylating agents (HMAs; azacitidine or decitabine) is standard therapy for newly diagnosed AML patients ineligible for intensive chemotherapy (IC). Figure. Overall Survival of Patients with Newly Diagnosed FLT3-ITD Mutated AML."

Acute Myelogenous Leukemia • Cardiovascular • Febrile Neutropenia • Heart Failure • Hypertension • Hypotension • Infectious Disease • Mucositis • Musculoskeletal Diseases • Neutropenia • Orthopedics • Pneumonia • Respiratory Diseases • Septic Shock • Stomatitis • DNMT3A • FLT3 • NPM1 • RUNX1

Cytomolecular mechanisms of relapse after frontline FLT3 inhibitor (FLT3i)-based therapy in FLT3-mutated (mut) acute myeloid leukemia (AML). (ASCO 2025) - "Induction therapy was intensive chemotherapy (IC) in 107 pts and low intensity therapy (LIT) in 165 pts [including HMA+venetoclax(VEN)+FLT3i in 93 pts]. FLT3i's used were gilteritinib (n=105), sorafenib (n=96), quizartinib (n=54), midostaurin (n=16), and crenolanib (n=1)... Loss of FLT3 mut at relapse occurred in almost 50% of pts receiving frontline FLT3i and was more common in pts receiving IC+FLT3i or HMA+VEN+FLT3i. Common mechanisms of clonal evolution included emergent mutations in RAS pathway, WT1, and DNA methylation genes (TET2, IDH1/2). Mutational clonal evolution was less frequent in post-ASCT relapses."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • FLT3 • IDH1 • IDH2 • TET2 • WT1

Quizartinib in combination with decitabine and venetoclax for newly diagnosed and relapsed/refractory FLT3-mutated AML. (ASCO 2026) - P1/2 | "Clinical Trial Registration Number: NCT03661307 Background: Hypomethylating agents (HMAs; azacitidine/decitabine) plus venetoclax (VEN) are standard for newly diagnosed acute myeloid leukemia (AML) unfit for intensive chemotherapy; however FMS-like tyrosine kinase-3 internal tandem duplication (FLT3-ITD) confers resistance and poor overall survival (OS). QUIZ+decitabine+VEN combination resulted in high CR/CRi, deep MRD responses, and encouraging survival in older pts with newly diagnosed FLT3-ITD AML."

Combination therapy • Acute Myelogenous Leukemia • Febrile Neutropenia • Heart Failure • Hypertension • Hypotension • Infectious Disease • Mucositis • Musculoskeletal Diseases • Neutropenia • Orthopedics • Pneumonia • Respiratory Diseases • Septic Shock • Stomatitis • DNMT3A • FLT3 • NPM1 • RUNX1

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

QUIZARTINIB WITH DECITABINE AND VENETOCLAX (TRIPLET) IS ACTIVE IN PATIENTS WITH FLT3-ITD MUTATED ACUTE MYELOID LEUKEMIA - A PHASE I/II STUDY (EHA 2022) - "Of 23 pts with R/R AML (median 3 prior Rx, 78% with ≥1 prior FLT3i including prior gilteritinib in 70%, and 39% had a prior alloSCT), 78% achieved CRc (3 CR, 15 CRi) with 6/16 and 5/18 responders achieving FLT3-PCR and multicolor flow cytometry negativity, respectively. Interestingly, RAS/MAPK mutations but not emergent TKD mutations were associated with primary and secondary resistance to the triplet. Accrual continues and updated clinical, NGS and mass cytometry (CyTOF) data will be presented."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Malignancies • Infectious Disease • Neutropenia • Respiratory Diseases • FLT3

Comparative Efficacy and Safety of FLT3 Inhibitor–Based Frontline Regimens in Newly Diagnosed FLT3-Mutated Acute Myeloid Leukemia: A Systematic Review and Network Meta-Analysis (SOHO 2026) - "Introduction: The rapid expansion of FLT3 inhibitors (FLT3i) and venetoclax (VEN)-based combinations has transformed the frontline landscape for FLT3-mutated AML...Gilteritinib-based triplets achieved the highest complete response/ complete remission with incomplete count recovery (CR/Cri) rates (OR, 3.15; 95% CI, 2.10–4.72) and measurable residual disease negativity (OR, 2.80; 95% CI, 1.65–4.75) vs midostaurin + 7+3, although OS benefit was partially offset by early mortality. For hypomethylating agent backbones, VEN + FLT3i triplets outperformed VEN + AZA (azacitidine) doublets in event-free survival (HR, 0.68; 95% CI, 0.49–0.94)... While triplet therapies offer the deepest molecular responses, quizartinib-based intensive induction currently represents the most favorable balance of survival and safety for fit patients; notably, the overall risk of bias across included studies was low. 7+3: 7 days of cytarabine and an anthracycline for the first 3 days, ASH: American..."

Retrospective data • Review • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3

Postmarketing Safety Signals of Revumenib (Menin-KMT2A Inhibitor) vs Acute Myeloid Leukemia-Targeted Therapies: A Class-Restricted Disproportionality Analysis of the FDA Adverse Event Monitoring System (2016–2026) (SOHO 2026) - " AE reports (January 2016–April 2026) were extracted for revumenib (n = 716) and eight targeted AML therapies (n = 70179): ziftomenib, enasidenib, ivosidenib, olutasidenib, gilteritinib, midostaurin, quizartinib, and venetoclax. Analysis of 716 revumenib reports (median age, 50 years; 50.2% male; 57.5% US-sourced; 55.6% serious) identified AML as the recorded indication in 59.2% of cases. Eleven AEs qualified as robust signals. Established toxicities included differentiation syndrome (n = 32; ROR, 9.12; 95% CI, 6.31–13.20), QTc prolongation (n = 29; ROR, 8.88; 95% CI, 6.03–13.08), and decreased platelet count (n = 113; ROR, 3.91; 95% CI, 3.19–4.79)."

Adverse events • Clinical • P4 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • KMT2A

Phase I/II Study of Quizartinib, Venetoclax, and Decitabine Triple Combination in FLT3-ITD Mutated AML (ASH 2024) - "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...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 allogeneic stem cell transplantation (ASCT)...In the frontline setting, 95% of pts achieved CRc with a median platelet and ANC recovery of 36 and 40 days, and a median OS not reached. The study continues to accrue, and updated results will be reported at the meeting."

P1/2 data • Acute Myelogenous Leukemia • Febrile Neutropenia • Gastrointestinal Disorder • Infectious Disease • Neutropenia • Pneumonia • Respiratory Diseases • Septic Shock • FLT3

Strategies to prevent post-transplant relapse in acute myeloid leukemia and myelodysplastic syndromes. (PubMed, Int J Hematol) - "Hypomethylating agents (HMAs) are biologically attractive and feasible with post-transplant-adapted dosing, but prophylactic azacitidine did not improve relapse-free or overall survival in a randomized trial. Newer decitabine-based, oral HMA, and venetoclax-containing strategies require confirmation...The QuANTUM-First trial supports quizartinib throughout induction, consolidation, and continuation, including after transplantation, whereas the MORPHO trial directly evaluated post-transplant gilteritinib and identified its clearest benefit in patients with detectable peri-transplant FLT3-internal tandem duplication (FLT3-ITD) MRD. This review traces the evolution of relapse prevention strategies and proposes a practical framework integrating baseline risk, serial MRD assessment, targetable biology, immune intervention, and post-transplant feasibility."

Journal • Review • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • FLT3

Novel targeted therapy and cellular immunotherapy enabling allogeneic hematopoietic stem cell transplantation for relapsed/refractory acute myeloid leukemia. (PubMed, Chin Med J (Engl)) - "For R/R AML patients with mutated FMS-related tyrosine kinase 3 (FLT3), sorafenib and quizartinib have shown encouraging therapeutic effects either in combination with chemotherapy for bridging to transplantation or as maintenance therapy after HSCT. Ivosidenib and enasidenib, which are inhibitors that target mutated isocitrate dehydrogenase (IDH) 1 and 2, respectively, have been approved by the US Food and Drug Administration (FDA) for the treatment of IDH1/IDH2-mutated R/R AML. Venetoclax, an inhibitor of B-cell lymphoma-2 (BCL2), is widely used in the salvage treatment of R/R AML and has better therapeutic effects and controllable drug toxicity than traditional chemotherapy. In addition, chimeric antigen receptor (CAR) T-cell immunotherapy (targeting CD33, CD123, and CLL1) has achieved encouraging clinical response rates in phase I and phase II clinical trials for R/R-AML, and subsequent bridging HSCT has significantly improved patient survival."

IO biomarker • Journal • Acute Myelogenous Leukemia • B Cell Lymphoma • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Transplantation • BCL2 • CD123 • CD33 • FLT3 • IDH1 • IDH2 • IL3RA

UPDATED RESULTS OF VEN-A-QUI STUDY: A PHASE 1-2 TRIAL TO ASSESS THE SAFETY AND EFFICACY OF TRIPLETS FOR NEWLY DIAGNOSED UNFIT AML PATIENTS: AZACITIDINE OR LOW-DOSE CYTARABINE WITH VENETOCLAX AND QUIRZATINIB (EHA 2023) - "Aims: To explore the safety and efficacy of VEN-AZA or VEN-LDAC in combination with Quizartinib (QUI) (VEN-A-QUI trial; EUDRACT2020-000406-28), in phase 1-2 clinical trial. Triplets (VEN-AZA-QUI or VEN-LDAC-QUI) for newly diagnosed unfit AML pts could be feasible with substantial VEN reduction. FLT3-ITD + pts and HMA naïve have not reached median OS. Final analyses with more follow-up will clarify the potential benefit of these triplets."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Cerebral Hemorrhage • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Thrombocytopenia

EP0042, a Dual FLT3 and Aurora Kinase Inhibitor: Preliminary Results of an Ongoing Phase I/IIa First in Human Study in Patients with Relapsed/Refractory Acute Myeloid Leukemia (ASH 2022) - "EP0042 has resulted in inhibition of tumor growth in FLT3-ITD and FLT3-ITD-TKD human tumor xenograft models and in quizartinib-resistant primary AML samples (Moore A et al...5 pts received a prior FLT3 inhibitor including midostaurin, gilteritinib or sorafenib...The dose escalation is continuing at intermittent and continuous dosing to establish the MTD and optimal RP2D dose for further evaluation. Once a RP2D is confirmed, a single arm dose expansion is planned in FLT3 mutated and wild type R/R AML, and the combination of EP0042 with other agents will be explored."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Ataxia • Fatigue • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Movement Disorders • Neutropenia • Oncology • AURKB • FLT3 • STAT5

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

A Phase II Randomized Trial Comparing Low-Dose Cytarabine and Venetoclax +/- Midostaurin in Non-Adverse Cytogenetic Risk Acute Myeloid Leukemia: The ALLG AMLM25 Intervene Trial (ASH 2024) - "Background For fit patients (pts), combining kinase inhibitors (midostaurin, quizartinib) with intensive chemotherapy is standard of care for FLT3mutated AML...Clonal evolution of kinase-activating mutations, including FLT3-ITD is an important mechanism of treatment failure in pts with non-adverse (NON-ADV) cytogenetic risk AML receiving frontline therapy with azacitidine and venetoclax (AZA-VEN) (DiNardo and Tiong et al, Blood 2020). Incorporating kinase inhibitors (e.g. gilteritinib) into less-intensive VEN-based regimens in unfit, older pts has been challenging, with cumulative myelosuppression a dominant issue (Short et al, JCO 2024)...Posaconazole antifungal prophylaxis was permitted with dose adjustment of VEN to 50 mg daily and MIDO to 50 mg daily due to increased risk of cardiac toxicities in older populations...FLT3­-ITD MRD clearance was observed in 9/15 (60%) in the LVM arm and 1/4 (25%) in the LV arm. Conclusion In unfit, older pts ≥60 years with newly..."

Clinical • P2 data • Acute Myelogenous Leukemia • Constipation • Febrile Neutropenia • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Neutropenia • FLT3

NCI-2018-01789: Quizartinib, Decitabine, and Venetoclax in Treating Participants With Untreated or Relapsed Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome (clinicaltrials.gov) - P1/2 | N=73 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Suspended ➔ Recruiting

Enrollment open • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • FLT3 • TP53

Efficacy and Safety of FLT3 Inhibitors in FLT3-Mutated Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (SOHO 2026) - "FLT3 inhibitors significantly improve OS, remission rates, and relapse-free survival in FLT3-mutated AML across all disease settings. Gilteritinib and quizartinib demonstrate superior FLT3 selectivity and efficacy to sorafenib in the ND and R/R settings. MRD status emerges as a critical modifier of post-HCT maintenance benefit."

Retrospective data • Review • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3

Multicenter upfront randomized phase II trial of quizartinib and high-dose cytarabine plus mitoxantrone in relapsed/refractory acute myeloid leukemia with FMS-like tyrosine kinase 3 internal tandem duplication. (PubMed, Haematologica) - "Not available."

Journal • P2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3

A Potent Small Molecule Inhibitor of FLT3, PHI-101 Overcomes Resistance in Acute Myeloid Leukemia: Efficacy and PK/PD Profile in Phase 1 First in Human Study (ASH 2022) - P1a/1b | "Seventy percent of enrolled patients had more than 3 prior anti-leukemic treatment attempts, and four patients had relapsed or refractory disease after treatment with other FLT3 inhibitors including gilteritinib, quizartinib, or HM43239. A dose-escalating phase 1a clinical data of PHI-101, which reflects up to cohort 4 of the study, indicates that PHI-101 generated potent FLT3 inhibition leading to encouraging anti-leukemic responses in R/R AML patients, including in those with prior FLT3 TKI therapeutic failure. PHI-101 showed good tolerance and favorable safety profile and reduced leukemic blasts significantly with 28-day dosing. PHI-101 sustained its activity to clear FLT3-ITD and/or FLT3-TKD mutations including D835Y or N676K identified in AML patients."

Clinical • P1 data • PK/PD data • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • FLT3

The type I FLT3 inhibitor XL999 overrides secondary FLT3-ITD mutations that arise under gilteritinib and quizartinib treatment in acute myeloid leukemia. (PubMed, Mol Biomed) - "Furthermore, XL999 demonstrated robust efficacy in patient-derived xenograft models, complemented by a favorable oral bioavailability profile. Together, these findings suggest that XL999 may represent an orally bioavailable FLT3 inhibitor with the potential to overcome clinically relevant secondary resistance mutations in FLT3-ITD-positive AML, supporting its further investigation as a therapeutic candidate."

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