Vanflyta (quizartinib) / Daiichi Sankyo - LARVOL DELTA

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). (ASCO 2025) - P3 | "Clinical Trial Registration Number: 2023-507936-20-00; NCT06578247 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

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

Autophagy inhibition overcomes resistance to FLT3 inhibitors in FLT3-ITD acute myeloid leukemia models (AACR 2025) - "In MOLM13 and MV4-11 (FLT3-ITD mutated cell lines), the administration of FLT3i first (midostaurin) or second (quizartinib) generation significantly elevates autophagic flux by inducing the formation of acidic vesicular organelles visualized by flux cytometry. In conclusion, FLT3i induces autophagy flux, limiting drug inhibitory activity, and autophagy inhibition can enhance the antileukemic effect of FLT3i and reverts cellular resistance. Analysis of the autophagic profile in AML can play a crucial role in individualized treatment."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CASP3 • FLT3 • STAT5 • STAT5AWqe

Combination of inhibitors of RAD51 and FLT-3 and other tyrosine kinase inhibitors synergistically inhibits proliferation of cultured human leukemia cell lines (AACR 2025) - "IBR2, an inhibitor of the DNA repair protein RAD51, was previously demonstrated to enhance the antiproliferative activity of imatinib against the CML blastoid cell line K562 (EMBO Mol Med 5: 353-365, 2013...In our studies, IBR2 enhanced the antiproliferative activity of regorafenib, an inhibitor of multiple tyrosine kinases, in a concentration-dependent manner by up to 80% against K562 cells (J Pharmacol Expt Ther, 364: 46-54, 2018...These findings suggest that: (1) the combination of quizartinib and a RAD51-inhibitor could be a useful treatment against FLT-3-wt AML; (2) quizartinib and gilteritinib may not act in exactly the same way against the FLT-3 target or other related targets; (3) novel combinations of a RAD51 inhibitor with non-traditional treatments for CML may provide a potential improvement in outcome for CML blast crisis; (4) RAD51 inhibitors may be active as monotherapy in myeloid leukemias. The combination of JKYN-1-mesylate with FLT-3 inhibitors under..."

Preclinical • Acute Myelogenous Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • RAD51

Identification of proteins in the oncogenic FLT3-ITD signaling pathway using the APEX2 system (AACR 2025) - "Given that quizartinib, an FLT3 inhibitor, alters the localization of FLT3-ITD protein to the cell surface, a quizartinib-treated group was used to mimic wild-type FLT3 and designated as pseudo-wild-type FLT3...To summarize, we leveraged exploratory proteomics to uncover a panel of candidate FLT3-ITD effectors based on their association or proximity with FLT3-ITD. Future studies will investigate the role of these proteins in FLT3-ITD-induced transformation."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • APEX2 • CHEK1 • FLT3 • GSPT1

Lintuzumab-Ac225 has potent mutation agnostic antileukemic activity in preclinical models of AML (AACR 2025) - "In clinical trials, lintuzumab-Ac225 had positive responses when combined with CLAG-M chemotherapy in relapsed/refractory AML patients, including those with high-risk features like venetoclax resistance and TP53 mutations...FLT3 inhibitors (gilteritinib, quizartinib), KMT2A inhibitors (revumenib, ziftomenib) and azacitidine were evaluated as single agents and in combination with Lintuzumab-Ac225... Lintuzumab-Ac225 shows broad anti-leukemic activity in AML cell lines, in a mutation (FLT3, KMT2A, NPM1, TP53) agnostic manner. It improves AML control in high-risk cases and enhances response durability when combined with standard of care treatments. These findings support its potential as a backbone therapy for relapsed/refractory AML, warranting further clinical evaluation."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD33 • CDKN1A • FLT3 • KMT2A • NPM1 • TP53

HPB-092: A novel FLT3 and IRAK4 dual inhibitor for the treatments of AML and MDS (AACR 2025) - "Compared to the approved FLT3 inhibitors gilteritinib and quizartinib, and the clinical-stage FLT3/IRAK4 dual inhibitor CA-4948, HPB-092 showed comparable or superior inhibitory potency against mutated forms of FLT3, improved IRAK4 inhibition, better selectivity, minimal inhibition of CYP3A4, no hERG activity, and an overall favorable safety profile, potentially benefiting a broader range of hematological malignancies. HPB-092 has received FDA clearance for a phase 1 dose-escalation and expansion study to assess its safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy in adult patients with relapsed or refractory AML, particularly those with FLT3 mutations and U2AF1 or SF3B1 mutations, at a leading cancer center in the US."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CYP3A4 • FLT3 • IRAK4 • SF3B1 • U2AF1

REAL-WORLD MULTICENTER INTERNATIONAL EXPERIENCE OF FLT3-INHIBITORS POST-TRANSPLANT MAINTENANCE AFTER ALLOGENIC HEMATOPOIETIC STEM CELL TRANSPLANTATION IN PEDIATRIC ACUTE MYELOID LEUKEMIA WITH FLT3-ITD (EBMT 2025) - "All patients were in complete remission before TKI initiation post-HSCT.Post-transplant maintenance was started after a median of 86 days [30-357] with either sorafenib (n=31), gilteritinib (n=6), midostaurin (n=2) or quizartinib (n=2). This study confirmed feasibility of post-transplant maintenance with FLT3 inhibitors. Toxicity was manageable, mainly hematologic not uncommon in the post-transplant settings. Careful dosing at introduction should be proposed."

Clinical • Post-transplantation • Real-world • Real-world evidence • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Neutropenia • Oncology • Pediatrics • Transplantation • FLT3 • KMT2A • NUP214 • NUP98 • WT1

Anti-Tumor Effects of Gilteritinib on FLT3 Mutations: Insights into Resistance Mechanisms in Ba/F3 Cell Models. (PubMed, Onco Targets Ther) - "These findings highlight the potent efficacy of gilteritinib against a wide range of FLT3 mutations, including TKD-PM and JMD-PM, as well as those associated with resistance to quizartinib or midostaurin. This comparative analysis underscores the need for tailored therapeutic strategies in AML treatment, emphasizing the clinical significance of gilteritinib in overcoming drug resistance."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • STAT5

NCI-2020-05261: Azacitidine and Quizartinib for the Treatment of Myelodysplastic Syndrome or Myelodysplastic/Myeloproliferative Neoplasm With FLT3 or CBL Mutations (clinicaltrials.gov) - P1/2 | N=58 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Dec 2025 ➔ Dec 2027 | Trial primary completion date: Dec 2025 ➔ Dec 2027

Trial completion date • Trial primary completion date • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology • ASXL1 • FLT3 • TP53

QUANTUM-WILD: PHASE 3, RANDOMIZED, DOUBLE-BLIND QUIZARTINIB STUDY IN NEWLY DIAGNOSED, FLT3-ITD–NEGATIVE ACUTE MYELOID LEUKEMIA (EBMT 2025) - P3 | "The induction phase involves the standard "7+3" regimen of cytarabine on Days 1–7 and an anthracycline on d1–3, then Quiz or PBO from d8–21; a second induction is allowed if bone marrow blast count is ≥ 5% after the first induction. N/A Clinical Trial Registry: NCT06578247 - Study Details; Quizartinib or Placebo Plus Chemotherapy in Newly Diagnosed Patients With FLT3-ITD Negative AML; ClinicalTrials.gov"

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

CircTADA2A stabilizes p53 via interacting with TRIM28 and suppresses the maintenance of FLT3-ITD acute myeloid leukemia. (PubMed, Leukemia) - "Importantly, in vitro transcription of circTADA2A and in vivo delivery via lipid nanoparticles (LNPs) significantly enhance the elimination of FLT3-ITD leukemia cells in combination with quizartinib treatment. In conclusion, our work uncovers the crucial functions of circTADA2A in the maintenance of FLT3-ITD AML and highlights a translationally important circTADA2A-based therapeutic approach for FLT3-ITD AML treatment."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Targeted Protein Degradation • FLT3 • TRIM28

Meta-analysis of Therapeutic Approaches in Acute Myeloid Leukemia: Unveiling Trends and Predictors of Treatment Response. (PubMed, Am J Clin Oncol) - "Chemotherapy, targeted therapy, and immunotherapy are valuable treatment options for AML patients. However, the efficacy of these AML treatments may vary depending on AML status and patient characteristics such as age and cytogenetic risk."

Journal • Retrospective data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Inhibition of PINK1 senses ROS signaling to facilitate neuroblastoma cell pyroptosis. (PubMed, Autophagy) - "Specifically, inhibition of PINK1 by AC220 or knockout of PINK1 impairs mitophagy and enhances ROS production, leading to oxidation and oligomerization of TOMM20, followed by mitochondrial recruitment and activation of BAX. Furthermore, inhibition or deficiency of PINK1 potentiates the anti-tumor effects of the clinical ROS-inducing drug ethacrynic acid (EA) to inhibit neuroblastoma progression in vivo. Therefore, our study provides a promising intervention strategy for neuroblastoma through the induction of pyroptosis."

Journal • CNS Tumor • Neuroblastoma • Oncology • Solid Tumor • CASP3 • GSDME

302: Maintenance Therapy in AML: A Trailblazing Slam Dunk, or a Flagrant Foul (HOPA 2025) - "While oral azacitidine gained approval based on the QUAZAR study, unanswered questions remain regarding the data and its real-world application. Similarly, conflicting data on FLT3 inhibitors (gilteritinib, sorafenib, midostaurin, quizartinib) in the pre- and post-transplant settings fuel ongoing debates over agent selection, toxicity, and quality of life...Compare the current standard of continuous venetoclax-based therapy to alternative approaches, such as fixed-duration treatment or measurable residual disease-guided discontinuation5. Identify toxicity management strategies for maintenance therapies used in AML"

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • IDH1 • IDH2

Multi-omics integration reveals immune hallmarks and biomarkers associated with FLT3 inhibitor sensitivity in FLT3-mutated AML. (PubMed, Blood Sci) - "We further evaluated the drug sensitivity of FLT3-mutant patients to 3 FDA-approved FLT3i, gilteritinib, midostaurin, and quizartinib, and observed heightened sensitivity in FLT3-mutant cohorts, accompanied by the activation of immune-related pathways in treatment-responsive groups. These biomarkers were consistently upregulated in favorable prognostic subgroups and demonstrated strong correlations with immune activation pathways. The identification of CD36, SASH1, and NIBAN2 as predictive biomarkers offers a novel toolset for stratifying FLT3i response and prognosis."

Biomarker • Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Inflammatory Arthritis • Leukemia • Oncology • CD36 • FLT3 • SASH1 • SCARB1

Impact of hematopoietic cell transplantation and quizartinib in newly diagnosed patients with acute myeloid leukemia and FMS-like tyrosine kinase 3-internal tandem duplications in the QuANTUM-First trial. (PubMed, Haematologica) - P3 | "Patients who underwent protocol-specified allo-HCT in CR1/CRc1 experienced post-allo-HCTQrelated complications, mostly grade ≥2 graft-versus-host disease, as expected. This posthoc analysis further supports quizartinib and allo-HCT in CR1/CRc1 as an efficacious and well-tolerated treatment strategy for newly diagnosed FLT3-ITDQpositive AML patients fit for intensive chemotherapy."

Journal • Acute Myelogenous Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • Transplantation • FLT3

Impact of hematopoietic cell transplantation and quizartinib in newly diagnosed patients with acute myeloid leukemia and FMS-like tyrosine kinase 3-internal tandem duplications in the QuANTUM-First trial (Haematologica) - P3 | N=539 | QuANTUM-First (NCT02668653) | Sponsor: Daiichi Sankyo | "Multivariable analyses revealed quizartinib treatment and allo-HCT in either CR1 (hazard ratio [HR]=0.553, 95% confidence interval [CI]=0.383Q0.798, P=0.0015 and HR=0.527, 95% CI=0.349Q0.796, P=0.0023, respectively) or CRc1 (HR=0.645, 95% CI=0.470Q0.886, P=0.0068 and HR=0.557, 95% CI=0.391Q0.793, P=0.0012, respectively) as significant predictive factors for a longer OS. No new safety signals were identified."

P3 data • Acute Myelogenous Leukemia

Study of Quizartinib in Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) (clinicaltrials.gov) - P1 | N=7 | Completed | Sponsor: Daiichi Sankyo Co., Ltd. | Phase classification: P1b ➔ P1

Phase classification • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Advances and Challenges in Quizartinib-Based FLT3 Inhibition for Acute Myeloid Leukemia: Mechanisms of Resistance and Prospective Combination Therapies. (PubMed, Eur J Haematol) - "Additional studies are required to determine the optimal FLT3I-based combinations, reduce resistance emergence, and improve outcomes. This review highlights the current state of FLT3I therapy, ongoing challenges with resistance, and future directions in optimizing treatment for FLT3-mutated AML, focusing on quizartinib."

IO biomarker • Journal • Review • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • AXL • FLT3 • STAT5

STING mediates increased self-renewal and lineage skewing in DNMT3A-mutated hematopoietic stem/progenitor cells. (PubMed, Leukemia) - "Notably, targeting STING showed inhibited acute myeloid leukemia (AML) development in a Dnmt3a-KO; Flt3-ITD AML model, comparable to AC220, an FDA-approved FLT3-ITD inhibitor. A patient-derived xenograft (PDX) model further demonstrated that targeting STING effectively alleviates the leukemic burden of DNMT3A-mutant AML. Collectively, our findings highlight a critical role for STING in hematopoietic disorders induced by DNMT3A mutations and propose STING as a potential therapeutic target for preventing the progression of DNMT3A mutation-associated leukemia."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • DNMT3A • FLT3 • STING

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Myeloid/Lymphoid Neoplasms with Eosinophilia and Tyrosine Kinase Gene Fusions, Version 1.2025. (NCCN)

NCCN guideline • Chronic Myelomonocytic Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm

IHCH9033, a novel class I HDAC inhibitor, synergizes with FLT3 inhibitor and rescues quizartinib resistance in FLT3-ITD AML via enhancing DNA damage response. (PubMed, Exp Hematol Oncol) - "Our study shows that IHCH9033, a novel class I HDACi with a desirable pharmacological profile, is a promising drug candidate for FLT3-ITD AML, and suggests a strategy of combining class I HDACis and FLT3is in AML clinical trials to increase efficacy and overcome resistance, thus potentially providing a curative treatment option."

Journal • Acute Myelogenous Leukemia • Gene Therapies • Hematological Malignancies • Leukemia • Oncology • Targeted Protein Degradation • CDC37 • FLT3 • HSP90AA1

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

New P2 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Conventional type 1 dendritic cells in the lymph nodes aggravate neuroinflammation after spinal cord injury by promoting CD8+ T cell expansion. (PubMed, Mol Med) - "Migratory cDC1s and resident cDC1s promote the expansion of CD8+ T cells in LNs around the injured spinal cord and mediate the adaptive immune response to aggravate neuroinflammation in SCI."

Journal • CNS Disorders • Inflammation • Orthopedics • CD8 • FLT3 • IFNG • ITGAE

Concurrent inhibition of p300/CBP and FLT3 enhances cytotoxicity and overcomes resistance in acute myeloid leukemia. (PubMed, Acta Pharmacol Sin) - "Targeting p300/CBP with A485 or CCS1477 retained the efficacy of quizartinib, suggesting marked synergy when combined with p300/CBP inhibitors in quizartinib-resistant AML models, as well as primary FLT3-ITD+ AML samples. These results demonstrate a potential therapeutic strategy of combining p300/CBP and FLT3 inhibitors to treat FLT3-ITD and FLT3-TKD AML."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CREBBP • EP300 • FLT3 • MYC • STAT5