crenolanib (ARO-002) / AROG - LARVOL DELTA

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

Cladribine, idarubicin, and AraC (CLIA) combined with a FLT3 inhibitor in patients with newly diagnosed FLT3-mutated Acute Myeloid Leukemia: A pooled analysis of prospective trials (ASH 2025) - "Introduction The incorporation of FLT3 inhibitors, cladribine, and high-dose cytarabine have been shownto improve outcomes in pts with newly diagnosed FLT3-mutated AML...We present a pooled analysis of frontline trials ofintensive chemotherapy (IC) with CLIA in combination with FLT3 inhibitors, focused on outcomes by co-occurring mutations.Methods Patients (pts) 18-65 years with newly diagnosed FLT3-mutated AML, fit for IC, were enrolled onprotocol with CLIA (cladribine 5 mg/m2 IV D1-5, araC 1.5-2 g/m2 IV D1-5, idarubicin 10 mg/m2 IV D1-3) plusgilteritinib (gilt) or sorafenib (soraf)...31 pts (78%) underwent allogeneic stem cell transplant (SCT) in CR1 and 19 pts (61%) receivedpost-SCT maintenance: 8 soraf, 6 gilt, 4 crenolanib, 1 AZA/VEN.After a 68-month median follow-up for all pts, median OS was not reached (NR), with 2- and 4-year OS of67% and 62%...The mostcommon AE for CLIA/gilt were elevated ALT/AST (n=17), febrile neutropenia (n=11), and rash (n=11); themost..."

Retrospective data • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • ASXL1 • DNMT3A • FLT3 • IDH1 • IDH2 • KRAS • NPM1 • RUNX1 • SF3B1 • SRSF2 • TET2 • U2AF1 • WT1

Long-term results of a phase 2 trial of crenolanib combined with 7+3 chemotherapy in adults with newly diagnosed FLT3 mutant AML. (ASCO 2022) - P2, P3 | " Pts (≥ 18 yrs) with newly diagnosed FLT3-AML received 7+3 induction with cytarabine 100 mg/m2/d for 7 days and daunorubicin (DNR) (<60 yrs: 90 mg/m2; ≥60 yrs: 60 mg/m2) or idarubicin (IDA 12 mg/m2) for 3 days. Long-term outcomes of a phase 2 trial of crenolanib combined with 7+3 induction and consolidation in adults with newly diagnosed FLT3 mutant AML demonstrate high response rates (CRc 86%). With a median follow-up of 45 mos, median OS has not been reached. A phase 3 trial (NCT03258931) randomizing pts with newly diagnosed FLT3 mutant AML to crenolanib vs midostaurin with 7+3 is ongoing."

Clinical • P2 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Neutropenia • Transplantation • DNMT3A • FLT3 • NPM1 • TP53

Crenolanib and Intensive Chemotherapy in Adults With Newly Diagnosed FLT3-Mutated AML. (PubMed, J Clin Oncol) - "Crenolanib plus intensive chemotherapy in adults with newly diagnosed FLT3-mutant AML results in high rate of deep responses and long-term survival with acceptable toxicity. A randomized trial of crenolanib versus midostaurin plus chemotherapy in younger patients is ongoing."

Journal • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Transplantation • FLT3

Crenolanib plus salvage chemotherapy improves outcomes in FLT3-mutant and NPM1 co-mutated relapsed/ refractory (R/R) Acute Myeloid Leukemia (AML): Results from a randomized, placebo-controlled, double-blind trial (ASH 2025) - P3 | "2017-001600-29).Materials and Fit adults with R/R FLT3m AML were randomized 1:1 to salvage induction chemo (FLAG-IDA/HAM) +crenolanib (100 mg TID) or placebo, followed by intermediate-dose cytarabine consolidation + crenolanibor placebo, and (if eligible, hematopoietic stem cell transplantation (HSCT)) followed by crenolanib orplacebo monotherapy for up to 1 year. In this randomized, placebo-controlled, double-blind study, the addition of crenolanib to salvagechemotherapy met its primary endpoint, demonstrating a statistically significant improvement in EFS aswell as an improved CR/CRi rate and a trend toward improved OS over chemotherapy alone in 106 fitadult pts with heavily pre-treated R/R FLT3m AML. The benefit was more pronounced in pts withNPM1/FLT3 co-mutated disease (n=59), with statistically significant improvement seen in not onlyremission rate and EFS but in overall survival as well. This data supports the further development ofcrenolanib in adults with..."

Clinical • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Gastrointestinal Disorder • Hematological Malignancies • Infectious Disease • Leukemia • Pneumonia • Respiratory Diseases • Septic Shock • FLT3 • NPM1

Medicinal Insights Into FLT3 Inhibitors as Anticancer Agents: Current Status and Future Direction. (PubMed, Arch Pharm (Weinheim)) - "Second-generation FLT3 inhibitors such as gilteritinib and quizartinib displayed improved selectivity and durable efficacy...Clinical trials have explored some compounds such as crenolanib, momelotinib, and various novel molecules in combination regimens, which are enhancing remission rates...Future directions should focus on structure-guided design, rational combination therapies, and expanding applications to other FLT3-altered malignancies. This review integrates updated FLT3 biology, clinical outcomes, medicinal chemistry, and computational insights to support personalized FLT3-targeted treatment strategies."

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

Recent advances in the treatment of FLT3-mutated acute myeloid leukemia. (PubMed, Blood Res) - "In newly diagnosed AML, the addition of midostaurin or quizartinib to intensive induction chemotherapy has demonstrated significant improvements in overall survival (OS), event-free survival, and relapse-free survival, establishing these regimens as current standards of care...Maintenance therapy following allogeneic hematopoietic stem cell transplantation has emerged as a promising strategy, with evidence supporting the use of sorafenib and gilteritinib to reduce relapse risk and improve posttransplant outcomes. Recent clinical investigations have focused on novel combination approaches, particularly triplet regimens, incorporating FLT3 inhibitors, venetoclax, and hypomethylating agents, which have demonstrated encouraging responses and survival outcomes. Next-generation FLT3 inhibitors, including crenolanib and dapolsertib, are being evaluated in ongoing studies. These advances continue to improve outcomes in patients with FLT3-mutated AML and are expected to further..."

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

TRANSCRIPTIONALLY DEFINED AML CELL STATES ASSOCIATE WITH TREATMENT RESPONSE AND MICROENVIRONMENTAL REMODELING (EHA 2026) - "Projection of state-specific signatures onto bulk RNA- seq revealed heterogeneous patient-level enrichment and distinct associations with drug sensitivity, revealing state-specific sensitivity and resistance patterns (e.g. crenolanib sensitivity in cycling progenitors)...Venetoclax/azacitidine treatment differentially affected progenitor, stromal, and monocytic states, showing most persistence of the stress-adapted progenitors...Functional state stratification therefore extends beyond the traditional leukemic stem cell paradigm and provides a biologically grounded framework for refining therapeutic targeting in AML. Study design and overview"

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • CD34 • CD38

CREB–mediated pharmacologic antagonism is associated with adaptive escape from MAPK inhibition in melanoma (SID 2026) - "To identify antagonistic compounds, we subjected 5 BRAF* melanoma lines to a high-throughput screen of 1,600 broad-spectrum FDA-approved and advanced preclinical drugs, co-administered with dabrafenib + trametinib (D+T; 4.0/0.4 nM)...The top 5 ranking antagonistic drugs were Mocetinostat (E=0.92), CP673451 (E=0.88), Axitinib (E=0.76), Amuvatinib (E=0.74), and BX-795 (E=0.74)...Notably, this subset included 14 mechanistically related platelet-derived growth factor receptor inhibitors (PDGFRI: CP673451, Amavadin, Axitinib, Crenolanib, Nintedanib, Sorafenib, Linifanib, Tivozanib, Imatinib, Masitinib, Pazopanib, Motesanib, Sunitinib)...Comparative phosphokinome profiling across the 3 cell lines identified CREB phosphorylation at S133 as a conserved event, robustly suppressed by D+T but selectively rescued by PDGFRi co-treatment. Together, these data identify PDGFR inhibitors as a reproducible source of antagonism to BRAF+MEK-targeted therapy and nominate CREB phosphorylation..."

Melanoma • Solid Tumor

Tumor Treating Fields remain effective in therapy-resistant glioblastoma with kinome shifts revealing novel therapeutic opportunities (AACR 2026) - "We did find that TTFields were predicted to activate PDGFRα in both newly diagnosed and temozolomide-resistant GBM cells: when combined with TTFields, a blood brain barrier penetrant PDGFR inhibitor, crenolanib, significantly decreased GBM cell growth. Using the Novocure inovivo system, we plan to test these novel kinase inhibitor combinations with TTFields in mouse models bearing intracranial GBMs. We hope to identify a kinase inhibitor based treatment strategy that can be translated to the clinic to further improve TTFields mediated increases in patient survival."

Brain Cancer • Glioblastoma • Oncology • Solid Tumor • PDGFRA

Astrocytes reprogram radiation-resistant glioblastoma to reveal new therapeutic vulnerabilities (AACR 2026) - "Additionally, radiation induced a therapeutic vulnerability in GBM cells when co-cultured with astrocytes, not present in GBM monocultures, to selinexor, afatinib, altiratinib, and crenolanib, with strongest effects at intermediate astrocyte:GBM ratios (10:90, 50:50). In conclusion, our study demonstrates that the presence of astrocytes alone significantly influences GBM response to therapy, and radiation therapy can further expose collateral sensitivities driven by astrocyte signaling. Modeling and mechanistically dissecting these microenvironmental interactions is essential for identifying new avenues for combination therapies that may improve outcomes in a cancer type where innovation is urgently needed."

Brain Cancer • Glioblastoma • Oncology • Solid Tumor

FLT3 alterations and inhibition in triple negative B-cell adult acute lymphoblastic leukemia patients (AACR 2024) - "In vitro studies using 5 FLT3i [Gilteritinib (Gil), Midostaurin, Crenolanib, Sorafenib and Quizartibin] and Venetoclax (Ven) were conducted on pt primary cells and on TN and other B-ALL cell lines (MUTZ5, MHH-CALL4 Ph-like; NALM6; RS4; 11, 697, REH) and 2 AML cell lines (OCI-AML3 FLT3; MV-4-11 FLT3-ITD). We found 15 FLT3 mut in 14/131 TN B-ALL and in 1/43 Ph+ cases: 43.8% were TKD mut, 3 ITD mut, 3 splicing site mut,1 N-terminal, 1 juxta-membrane domain and 1 Ig-like site (Fig. FLT3 alterations identify a novel subgroup of TN B-ALL with therapeutic potential also in combination regimens. Ricerca Corrente Italian MoH L3P1946."

Clinical • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • CDKN2A • CREBBP • CSMD1 • FLT3 • IKZF1 • KDM6A • KMT2D • ZNF384

Study Investigating the Efficacy of Crenolanib With Chemotherapy vs Chemotherapy Alone in R/R FLT3 Mutated AML (clinicaltrials.gov) - P3 | N=106 | Completed | Sponsor: Arog Pharmaceuticals, Inc. | Recruiting ➔ Completed | N=322 ➔ 106 | Trial completion date: Oct 2024 ➔ Apr 2026 | Trial primary completion date: Oct 2024 ➔ Apr 2026

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3

Study of Crenolanib vs Midostaurin Following Induction Chemotherapy and Consolidation Therapy in Newly Diagnosed FLT3 Mutated AML (clinicaltrials.gov) - P3 | N=214 | Completed | Sponsor: Arog Pharmaceuticals, Inc. | Recruiting ➔ Completed | N=510 ➔ 214 | Trial completion date: Nov 2024 ➔ Apr 2026 | Trial primary completion date: Nov 2022 ➔ Apr 2026

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3

Disruption of gastrointestinal pdgfrα+ cells leads to loss of post-junctional inhibitory motor responses. (PubMed, Am J Physiol Gastrointest Liver Physiol) - "Purinergic inhibitory post-junctional motor responses were greatly attenuated in the GI tracts of crenolanib treated animals compared to vehicle treated controls in response to electric field evoked nerve stimulation. These data provide evidence for a functional role of PDGFRα+ cells in inhibitory neuroeffector motor responses throughout the gastrointestinal tract."

Journal • Gastrointestinal Disorder • Oncology • Solid Tumor • KIT • PDGFRA

Unveiling FLT3 in B-ALL: Molecular drivers and targeted treatment opportunities (ASH 2025) - "In vitro assays withincreasing concentrations of 6 FLT3i for 24, 48, 72h [Gilteritinib (Gil), Midostaurin, Crenolanib, Sorafenib,Quizartinib, Ponatinib (Pon)] and Venetoclax (Ven) were performed on primary patient samples (n=29; FLT3-mut n=5/29), 11 B-ALL wt cell lines, 2 B-ALL mut (NALM6-mut, KASUMI-10), and 4 AML cell lines (OCI-AML3 wt; MV-4-11, MOLM-13, MONO-MAC6 FLT3-mut). FLT3 alterations define a novel Ph-negative B-ALL subgroup withtherapeutic relevance. Given the responses in FLT3-wt in addition to the mutated models, FLT3i may alsobenefit patients without FLT3 muts. Thanks to: Ricerca Corrente by the Italian MoH L3P1946 andAILTreviso."

Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • T Acute Lymphoblastic Leukemia • FLT3 • IKZF1 • KMT2A • PBX1 • TCF3 • TP53 • ZNF384

Profiling drug sensitivity in CLL B cells after BTK inhibitor progression using a novel drug panel (ASH 2025) - " Using the Mayo Clinic CLL Database and the Mayo Clinic CLL Tissue Bank, we identified 47 patients with RR CLL, all of whom experienced disease progressionon a BTKi (35 ibrutinib +/- CD20 antibody, 10 acalabrutinib +/- CD20 antibody, 2 other)...We also observed that RR CLL cohort exhibited significantly increased drug resistance to most of the tested drugs in the presence of BMSCs with corresponding increases in IC50s (with vs. without BMSCs, fold-change respectively): LP-118 3.92-fold, venetoclax 1.98-fold, carfilzomib 2.58-fold, TP-0903 1.65-fold, panobinostat 204.23-fold, TCIP1 1.91-fold, crenolanib 1.31-fold, idasanutlin 1.69-fold, belinostat 6.14-fold, LP-168 1.29-fold, eprenetapopt 3.44-fold and GTE 1.08-fold (11 out of 12 with p -values <0.05 except for GTE which was not significant, Mann-Whitney U test)... Our results highlight the spectrum of currently available drugs that show promise for therapeutic use in patients with RR CLL who experience disease..."

IO biomarker • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • AXL • BCL2 • STAT6 • TP53

Comparative safety and efficacy of first- and second-generation FLT3 inhibitors in newly diagnosed and relapsed AML: A meta-analysis stratified by molecular biomarkers (ASH 2025) - "First-generation (sorafenib and midostaurin) and second-generation (gilteritinib, quizartinib, and crenolanib) FLT inhibitors demonstrated efficacy and safety across disease stages and are now used as a standard of treatment for FLT3-mutated AML. Conclusions Second-generation FLT inhibitors exhibit enhanced efficacy in relapsed-refractory AML scenarios and comparable outcomes to first-generation inhibitors in newly diagnosed AML.Stratification using ITD allelic ratio and NPM1 co-mutation is emerging as a critical factor. In light of these findings, it's imperative to integrate second-generation inhibitors in salvage settings and Biomarker-guided treatment decisions in front-line FLT3 mutant-AML"

Biomarker • Retrospective data • Acute Myelogenous Leukemia • Cardiovascular • Hematological Disorders • Hypertension • Neutropenia • FLT3 • NPM1

Determining sensitivity to FLT3 inhibitors prior to therapy in FLT3 mutant acute myelogenous leukemia (ASH 2025) - "For ex-vivo sensitivity assays, AML cells were treated with several dilutions of a FLT3i(Sorafenib, Midostaurin, Crenolanib, Quizartinib, Gilteritinib, Tuspetinib and MAX-40279 (a dualFLT3/FGFR inhibitor)) and cell viability was assessed with CellTiter-Glo® (Promega). Using our MS-based proteomics measurements and sensitivity results with our proprietary MLmodel, we processed both AML patient samples (N=57) and patient-derived cell lines (N=59), and wewere able to identify 7 distinct clusters. Previously we demonstrated that RPPA proteomics could discriminate FLT3i sensitive andresistant cases and here we present orthogonal confirmation by MS proteomics and ex-vivo sensitivityassays. Moreover, we show that the expression of only three proteins forms a robust biomarker topredict FLT3i sensitivity of FLT3-MUT AML patients prior to therapy. We also identified AML cell lines thatmimic both FLT3i resistance and sensitivity, and combined with deep proteomics data, these..."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • CD34 • FLT3 • PXN • SMARCA2

Negative feedback regulation of nfkb, MAPK, and JAK-STAT drives adaptive resistance to gilteritinib in AML (ASH 2025) - "Patients treated with highly selective inhibitors such asgilteritinib, crenolanib, and quizartinib usually relapse within eight to twelve months. These findings explain how elevated AP1 and NF-κB/JAK-STAT activitiestranscriptionally induce negative regulators to favor cellular survival, as unchecked MAPK signaling wouldotherwise trigger apoptosis. Collectively, these data strongly support the rationale for evaluating thecombination of gilteritinib and venetoclax with momelotinib as a therapeutic strategy to achieve effectiveand durable responses in AML."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • FLT3 • IRAK1 • MAPK8 • STAT5 • TET2

MODULE 3: Role of FLT3 Inhibitors in AML Management (ASH 2024) - "This program is supported by educational grants from AbbVie Inc, Astellas, and Daiichi Sankyo Inc.Pharmacologic similarities and differences among available FLT3 inhibitors for AML; implications for potency, activity and tolerability Principal findings from the Phase III QuANTUM-First study evaluating the addition of quizartinib to chemotherapy and its continuation as a single agent for patients with newly diagnosed AML with a FLT3-ITD mutation FDA approval of quizartinib for previously untreated AML with a FLT3-ITD mutation; clinical role Long-term outcomes reported with gilteritinib versus salvage chemotherapy for patients with relapsed/refractory (R/R) AML with a FLT3 mutation; optimal integration into routine practice Early data with gilteritinib combined with standard intensive chemotherapy or venetoclax-based therapy for AML with a FLT3 mutation Available data with and ongoing investigations of other novel FLT3 inhibitors, such as crenolanib and BMF-500, for AML..."

Acute Myelogenous Leukemia • FLT3

Optimizing FLT3 Inhibitor Use in Adult Acute Myeloid Leukemia with FLT3 Mutations Using Proteomics (ASH 2023) - "Of 137 with FLT3 ITD or D835 mutations, 54 who were treated with FLT3I (Sorafenib=22, Quizartinib=11, Midostaurine=6, Gilteritinib=4 and Crenolanib=1) combined with other agents (Hypomethylating agents (HMA)=23, HMA+Venetoclax (VTX)=5, Idarrubicin+Cytarabine (AraC)+Purine Analogs (IA+Pur)=19, IA+Pur+VTX=2, AraC=3, Fludarabine+AraC (FA)=1, none=1) were selected for analyses. Protein profiling identified cohorts of FLT3 mutant patients that achieved the highest benefit from FLT3I addition, regardless of all other clinical or molecular characteristics. We identified targetable proteins that are elevated in adverse signatures, and hypothesized that these may be targets for modulation to improve FLT3I response. Moreover, a small set of 6 proteins accurately classifies patients and could be used clinically to triage patients for treatment recommendation."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • AIF1 • AKT1 • AKT2 • ASXL1 • BBC3 • BCL2L11 • CD34 • CDKN2A • CEBPA • DDB1 • DNMT3A • FLT3 • IDH1 • NPM1 • PTPN11 • RHEB • SDHA • SIRT6 • SLFN11 • SMARCA2 • TET2 • TP53 • WT1

Efficacy and Safety of FLT-3 Inhibitors in Newly Diagnosed FLT-3 Mutated AML Patients: A Systematic Review of Clinical Trials (ASH 2023) - "85) significantly in favor of quizartinib (Qui) + low dose cytarabine (LDAC) vs. LDAC alone. In two nRCTs (N=63) on unfit patients, Qui + venetoclax (Ven) +Aza/LDAC showed complete response (CR)/overall response (ORR) of 42%/72% and Qui+Aza/LDAC showed CR/ORR of 44%/56%...5% with midostaurin (Mid)+ chemotherapy and chemotherapy, respectively...9% and 73% with Gil+chemotherapy and crenolanib (Cren) + chemotherapy, respectively... Addition of Gil, Qui, Lus, Mid, or Cren to standard therapy was well tolerated by most of the patients with FLT-3 mutation. Addition of Mid or Qui to chemotherapy significantly improved survival and response rates as compared to chemotherapy alone in fit patients with FLT-3 mutation and the results were consistent in both young and old fit patients. In early phase trials, Gil and Cren were effective in combination with chemotherapy in fit patients."

Clinical • Review • Acute Myelogenous Leukemia • FLT3

Crenolanib improves outcomes for AML patients with FLT3 and NPM1 mutations (Roswell Park Comprehensive Cancer Center) - "The findings of both studies will be presented...at the 67th annual meeting of the American Society of Hematology (ASH)....Of 106 patients enrolled in the study, 52 were assigned to receive crenolanib in addition to intensive chemotherapy, while 54 received chemotherapy and placebo. Those in the crenolanib group experienced a higher overall response rate (60% vs. 39%) and lower rate of treatment resistance (24% vs. 59%). At a median follow-up of 37.3 months, those who received crenolanib also had both longer event-free survival (3.4 vs. 0.0 months) and longer overall survival (10.4 vs. 8.7 months)."

P3 data • Acute Myelogenous Leukemia

High-Throughput Drug Repurposing Identifies SN-38 As a Potent Inhibitor of AML with Synergistic Effects in Combination with PARP and BCL-2 Inhibitors for Treating KMT2A-Rearranged Leukemias (ASH 2024) - "Results : High Throughput Drug Screening identified the top five most active FDA-approved drugs across 6 AML cell lines : 1) SN-38 (a topoisomerase I inhibitor and the active metabolite of irinotecan), 2) Triplotide (an NF-κB inhibitor), 3) Mitoxantrone (a topoisomerase II inhibitor), 4) Idarubicin (a topoisomerase II inhibitor), and 5) Bortezomib (a proteasome inhibitor)...Drugs that exhibited greater selectivity, meaning greater responses in KMT2Ar cell lines, included : 1) Ingenol Mebutate (a PKC inhibitor), 2) a BET bromodomain inhibitor, 3) MIK665 (an MCL1 inhibitor), 4) Prexasertib (a CHK inhibitor), and 5) Crenolanib (an FLT3/PDGFR inhibitor)...Moreover, the observed synergy with PARP and BCL-2 inhibitors reveals strategies to overcome AML resistance mechanisms to SN-38. However, rigorous preclinical and clinical studies are essential to validate its efficacy, safety, and optimal dosing regimens."

Combination therapy • IO biomarker • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia • AFF1 • FLT3 • KMT2A • MLLT3