azacitidine / Generic mfg. - LARVOL DELTA

Azacitidine, Venetoclax, and Revumenib for Newly Diagnosed NPM1-Mutated or KMT2A-Rearranged AML. (PubMed, J Clin Oncol) - P1/2 | "In older adults newly diagnosed with NPM1m or KMT2Ar AML, the combination of azacitidine, venetoclax, and revumenib was able to be safely administered with high rates of CR and clinical activity."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • KMT2A • NPM1

ALL-ORAL DECITABINE-CEDAZURIDINE (DEC-C) + VENETOCLAX (VEN) IN PATIENTS WITH NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA (AML) INELIGIBLE FOR INDUCTION CHEMOTHERAPY: PHASE 1/2 CLINICAL TRIAL RESULTS (EHA 2025) - P1/2 | "Background: In patients (pts) with AML aged ≥75 years or otherwise ineligible for induction chemotherapy (ICT), the combination of azacitidine (AZA) with the Bcl-2 inhibitor VEN is approved based on the VIALE-A trial (complete remission [CR] rate, 36.7%; median overall survival [mOS], 14.7 months); intravenous (IV) decitabine (DEC) + VEN is also approved in this setting. The all-oral regimen of DEC-C + VEN resulted in comparable safety, response, and survival rates to parenteral AZA + VEN in pts with newly diagnosed AML ineligible for ICT. Compared with standard dosing, early BM examination and subsequent dose reductions in DEC-C and/or VEN during post-remission treatment cycles were associated with improved long-term outcomes and tolerability. These data underscore the importance of regimen optimization and suggest a practice-changing role for oral DEC-C + VEN in this pt population with high unmet need."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Anemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology

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

Venetoclax (VEN) and azacitidine (AZA) with gilteritinib (GILT) in patients with newly diagnosed (ND) FLT3mut+ Acute Myeloid Leukemia (AML) ineligible for intensive induction chemotherapy (chemo): Interim results from the phase 1/2 VICEROY study (ASH 2025) - P1/2 | "Dosing holds wereclosely monitored during C1 after marrow response, and VEN/AZA/GILT duration was reduced onsubsequent cycles after remission. The phase 2 portion is ongoing and enrolling patients."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Cardiovascular • Febrile Neutropenia • Neutropenia • Thrombocytopenia • FLT3

Results from paradigm - a phase 2 randomized multi-center study comparing azacitidine and venetoclax to conventional induction chemotherapy for newly diagnosed fit adults with acute myeloid leukemia (ASH 2025) - "The study has met its primary endpoint. Aza-ven was associated with significantly improved EFS, as wellas higher rates of OR and CCR, vs IC in younger, IC-eligible pts. Overall survival data continue to mature."

Clinical • P2 data • Acute Myelogenous Leukemia • CNS Disorders • Depression • Hematological Malignancies • Infectious Disease • Leukemia • Psychiatry • Respiratory Diseases • Septic Shock • FLT3 • IDH1 • IDH2 • NPM1 • TP53

Ziftomenib in combination with venetoclax and azacitidine in relapsed/refractory NPM1-m or KMT2A-r acute myeloid leukemia: Updated phase 1a/b safety and clinical activity results from KOMET-007 (ASH 2025) - P1 | "In the ongoing KOMET-007 study, ziftomenib RP2D of 600 mg QD + Ven/Aza was welltolerated with robust clinical activity in patients with R/R NPM1-m or KMT2A-r AML. No ziftomenib-relatedQTc prolongation was reported. One case of DS (NPM1-m, Gr 3) successfully resolved with protocol-specified mitigation."

Clinical • Combination therapy • P1 data • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • FLT3 • KMT2A • NPM1

Tagraxofusp, azacitidine, and venetoclax (TAG-AZA-VEN) triplet therapy shows efficacy, tolerability, and transplant potential in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN): Results of a phase 2 trial (ASH 2025) - P1 | "Triplet therapy with TAG-AZA-VEN is effective and feasible in patients with previouslyuntreated or R/R BPDCN, including in an older patient population. The safety profile is consistent withprior studies of TAG and AZA/VEN, and triplet therapy does not add new AEs not seen with TAG orAZA/VEN. A high proportion of patients (1L and R/R) proceeded to transplant in remission."

Clinical • IO biomarker • P2 data • Atrial Fibrillation • Cardiovascular • CNS Disorders • Diabetes • Febrile Neutropenia • Hematological Malignancies • Infectious Disease • Neutropenia • Renal Disease • Thrombocytopenia • Transplantation • BCL2 • CD123 • IL3RA

Efficacy and safety of pivekimab sunirine in combination with venetoclax plus azacitidine in unfit patients with newly diagnosed Acute Myeloid Leukemia (ASH 2025) - "Unfit pts with newly diagnosed CD123-postive AML demonstrated high CR rates withPVEK+VEN+AZA. These robust response rates were observed across the select mutational profiles tested.Follow up with duration of response and survival estimates among all pts, by molecular subgroups andMRD negativity status, are being evaluated. Triplet therapy in unfit 1L pts with CD-123–positive AML waswell-tolerated, and no new safety signals were observed."

Clinical • Combination therapy • Acute Myelogenous Leukemia • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myocardial Infarction • Neutropenia • Respiratory Diseases • Thrombocytopenia • CD123 • IL3RA

Preliminary data from the ongoing Phase 1 study of the menin-MLL inhibitor enzomenib (DSP-5336) in combination with venetoclax and azacitidine in patients with relapsed or refractory Acute Myeloid Leukemia (ASH 2025) - P1/2 | "Median age was 50 yrs (21-76), 56% were female andmedian prior regimens was 2 (1-4); 3 pts (16.7 %) had prior allogeneic stem cell transplant (SCT), 6 pts(33.3%) had prior VEN, and 5 pts (27.8%) received prior menin inhibitor (2 ziftomenib, 1 revumenib, 2enzomenib). Preliminary data show ENZO up to 300 mg BID to be well tolerated in combination withVEN/AZA with no DLTs in 18 pts with R/R KMT2Ar or NPM1m AML. No QT prolongation was reported andthere was 1 report of non-serious DS. Promising preliminary clinical activity has been observed,particularly in pts without prior VEN or menin exposure (100% ORR and 67% CRc rate)."

Clinical • Combination therapy • P1 data • Acute Myelogenous Leukemia • Central Nervous System Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Leukopenia • Neutropenia • Septic Shock • Thrombocytopenia • FLT3 • KMT2A • NPM1

Ziftomenib in combination with venetoclax and azacitidine in newly diagnosed NPM1-m acute myeloid leukemia: Phase 1b results from KOMET-007 (ASH 2025) - P1, P3 | "In the ongoing KOMET-007 study, ziftomenib RP2D of 600 mg once daily combined withVen/Aza was well tolerated and demonstrated robust clinical activity in patients with newly diagnosedNPM1-m AML, including 84% CRc after a median of 3.5 weeks and 54% CRc MRD-negativity after amedian of 8.4 weeks. Low rates of ziftomenib-related cytopenia and no additional myelosuppressionwere observed with this combination. One case each of differentiation syndrome (grade 2) andinvestigator-assessed QTc (grade 3) were successfully resolved."

Combination therapy • P1 data • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • FLT3 • HEY1 • KMT2A • NPM1

Efficacy, molecular and translational analysis of TP53-mutated HR-MDS with bexmarilimab and azacitidine: Updated results from the bexmab Phase 1/2 study (ASH 2025) - "ConclusionBexmarilimab plus azacitidine shows encouraging activity in mTP53 HR MDS and translational datasupports potential for altering the immune dysregulation in mTP53 MDS. Updated clinical andtranslational data will be reported."

Clinical • P1/2 data • Hematological Malignancies • Myelodysplastic Syndrome • AVEN • CD8 • TP53

Updated response and safety analyses from a Phase 1 study of ivosidenib combined with intensive chemotherapy in patients with newly diagnosed (ND) Acute Myeloid Leukemia with isocitrate dehydrogenase (IDH)1 mutation (ASH 2025) - P1, P3 | "Introduction Ivosidenib (IVO) is approved as monotherapy and in combination with azacitidine for frontline treatmentof patients (pts) with mIDH1 acute myeloid leukemia (AML) unfit for intensive chemotherapy (chemo)...Pts with ND mIDH1AML received induction therapy: cytarabine 200 mg/m2/d × 7 d and either daunorubicin 60 mg/m2/d oridarubicin 12 mg/m2/d × 3 d (up to 2 cycles of induction were permitted) and IVO 500 mg once dailystarting on d 1 of induction therapy...IVO maintenance has an acceptable safety profile, is associated with stablenormalization of blood counts, and results in durable responses and long-term survival acrosscomutational profiles. The benefit of this frontline regimen is being assessed in a phase 3 randomized,blinded trial (NCT03839771)."

Clinical • P1 data • Acute Kidney Injury • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Leukopenia • Neutropenia • Renal Disease • Thrombocytopenia • TP53

γ9δ2 T-cell (γ9δ2TC) activation with ICT01 and azacitidine-venetoclax (Aza-Ven) induces high rates of remission and overall survival in patients with newly diagnosed (ND) acute myeloid leukemia (AML): Results from the phase 1/2 study eviction (ASH 2025) - P1/2 | "ICT01 was safe, well tolerated and generated very high CR and CRc rates in older/unfitpatients with ND-AML. Both the high response rate and the promising early OS signal which comparefavorably to recently published studies warrant further clinical investigation. Consistent PD effectssuggest an individual contribution of ICT01 to the efficacy of the novel triplet regimen ICT01-Aza-Ven."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Neutropenia • CD8 • IFNG • TNFA

Venetoclax combined with five days of azacitidine for the treatment of previously untreated Acute Myeloid Leukemia (AML): Initial results of the prospective venaza-5S trial (ASH 2025) - P2 | "In this high-risk patient population with a median age of over 81 years and nearly50% myelodysplasia-related AML, the VEN + AZA-5 regimen achieved a cCR-rate of 53%. While in theVIALE-A trial, a cCR-rate of 66% was reported for the combination of VEN with 7d of AZA, a directcomparison is problematic given the differences in baseline patient characteristics. More detailedanalysis of prognostic factors, responses in genetic subgroups including the ELN-2022 and 2024 riskcategories, and molecular responses will be presented at the meeting.The VenAZA-5 regimen appears to be an effective and well-tolerated front-line treatment option for olderor comorbid AML patients, and the 5-day schedule of AZA administration may be attractive for patientsand physicians."

Clinical • Acute Myelogenous Leukemia • Acute Promyelocytic Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Neutropenia • Thrombocytopenia

Phase I trial of a novel first-in-class drug ONC201 as a post-transplant maintenance for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) (ASH 2025) - P1 | "GVHD prophylaxis included tacrolimus and methotrexate with or withoutantithymocyte globulin. ONC201 was well tolerated with no observed DLT and a manageable safety profile. The AEprofile was not different from AEs expected in a post-transplant population. Rates of cytopeniaswere low."

Clinical • P1 data • Post-transplantation • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Hepatology • Immunology • Infectious Disease • Leukemia • Liver Failure • Myelodysplastic Syndrome • Neutropenia • Thrombocytopenia • Transplantation • ASXL1 • BCOR • DRD2 • STAG2 • TP53 • U2AF1

Results of the Phase 1B study of pegargiminase (ADI-PEG 20) in combination with AZA-VEN in newly diagnosed high-risk AML patients not candidates for intensive chemotherapy (ASH 2025) - P1 | "Pegargiminase (ADI-PEG 20), ametabolism-targeting therapeutic consisting of the arginine-degrading enzyme arginine deiminasecombined with polyethylene glycol, demonstrated high synergy with VEN-decitabine in pre-clinicalmodels and anti-leukemic activity as monotherapy and with cytarabine in clinical trials...We conducted a phase 1A/B trial evaluating triplet therapy with ADI-PEG 20+ azacitidine and venetoclax (AZA-VEN) in relapsed/refractory (R/R) and newly diagnosed (ND) AML(NCT05001828).MethodsThe phase 1A dose escalation cohort in R/R AML (n=13) was previously reported...Rates of CRc and MRD-negativity were high, with durableresponses observed. OS was better than expected, in this very-high risk AML population."

Clinical • Combination therapy • P1 data • Acute Myelogenous Leukemia • Infectious Disease • Pneumonia • Respiratory Diseases • ASS1 • FLT3 • KMT2A • NF1 • NRAS • PTPN11

Transfusion independence, hematological improvement and associated safety outcomes with bexmarilimab and azacitidine in HR-MDS: Results of the bexmab Phase 1/2 study (ASH 2025) - "In addition, pre-clinical datafrom Clever-1 knock-out and anti-Clever-1 treated mice suggests improved hematopoiesis andhematological recovery after 5-fluorouracil based chemotherapy. Altogetherthese data suggest that Clever-1 inhibition with the bexmarilimab combination enables hematopoieticrecovery in MDS patients. ConclusionMaintenance of baseline TI status, increased TI rate and increased number of BM progenitor cellsproducing platelets and RBCs, support bexmarilimab's unique mechanism of action in HR MDS,improving the efficacy of HMAs and supporting hematopoietic recovery, associated with lower rate ofadverse events."

Clinical • P1/2 data • Leukopenia • Myelodysplastic Syndrome • Neutropenia • AVEN

Genetic Risk Stratification and Outcomes Among Treatment-Naive Patients With AML Treated With Venetoclax and Azacitidine. (PubMed, Blood) - P1b, P3 | "ELN prognostic classifiers do not provide clinically meaningful risk stratification of OS outcomes for patients with AML treated with venetoclax-azacitidine. TP53, FLT3-ITD, NRAS, and KRAS mutation status allows classification of these patients into three risk groups with distinct differences in median OS."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • KRAS • NRAS • TP53

Subgroup analyses from the randomized, Phase 3 VERONA study of venetoclax with azacitidine (Ven+Aza) versus placebo with azacitidine (Pbo+Aza) in patients with treatment-naïve, intermediate and higher-risk Myelodysplastic Syndromes (HR MDS) (ASH 2025) - P3 | "VERONA did not meet the primary endpoint of OS. A higher proportion of patients treatedwith Ven+Aza achieved mOR, mCR+HI, and numerically lower risk of AML transformation vs those treatedwith Pbo+Aza. Subgroup analyses showed favorable trends in response for Ven+Aza vs Pbo+Aza inyounger patients, excess blasts, and select mutations."

Clinical • P3 data • Hematological Malignancies • Myelodysplastic Syndrome • ASXL1 • RUNX1 • TP53

Venetoclax and azacitidine versus CAG for unfit patients with newly diagnosed acute myeloid leukemia: A propensity score-matched analysis. (PubMed, Leuk Res) - "This study evaluated the clinical efficacy of venetoclax and azacitidine (VEN+AZA) versus CAG (cytarabine, aclarubicin, and granulocyte colony-stimulating factor) for newly diagnosed adult acute myeloid leukemia (AML) unfit patients. 31.7 % (P = 0.20). Patients with age ≥ 60 y (EFS, P = 0.032), ECOG≥ 2 (EFS, P = 0.047), secondary AML (OS, P = 0.015; EFS, P = 0.039), ELN intermediate-adverse karyotype (OS, P = 0.034; EFS, P = 0.044), RUNX1 mutation (OS, P = 0.003; EFS, P = 0.003) and IDH1/2 mutation (EFS, P = 0.039) showed a preference for VEN+AZA regarding OS, and patients with SRSF2 mutation favored CAG in OS (P = 0.031)."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • DNMT3A • IDH1 • IDH2 • RUNX1 • RUNX1T1 • SRSF2

CR109124: A Study of Bleximenib in Combination With Acute Myeloid Leukemia (AML) Directed Therapies (clinicaltrials.gov) - P1 | N=196 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • KMT2A • NPM1 • NUP214 • NUP98

Phase 1b/2 study of lisaftoclax (APG-2575) combined with azacitidine (AZA) in patients (pts) with treatment-naïve (TN) or prior venetoclax (VEN)-exposed myeloid malignancies. (ASCO 2025) - P1/2 | "LISA at different dose regimens combined with AZA provides promising treatment options for pts with HR-MDS or AML. No DLTs occurred. The MTD was not reached."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Febrile Neutropenia • Hematological Malignancies • Infectious Disease • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Septic Shock • Thrombocytopenia

γ9δ2 T-cell activation (γδTCA) with ICT01 combined with azacitidine-venetoclax (AV) for older/unfit adults with newly diagnosed (ND) AML: Preliminary efficacy and dose selection in phase 1/2 study EVICTION. (ASCO 2025) - P1/2 | "For AV combination, the recommended Phase 2 dose is 10 mg ICT01 Q4W. Both ICT01 regimens were safe and very well tolerated and generated very high CR and CR/CRi rates in older/unfit ND-AML pts. The high response rates seen in adverse risk pts warrant further clinical investigation."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Neutropenia • ASXL1 • DNMT3A • IDH1 • IDH2 • IFNG • JAK2 • NPM1 • NRAS • RUNX1 • SF3B1 • SRSF2 • STAG2 • TNFA • TP53 • U2AF1

VAG-3+7-G: VAG Versus Standard Chemotherapy With FLT3 Inhibitor in Adult Patients With FLT3-Mutated AML (clinicaltrials.gov) - P3 | N=300 | Not yet recruiting | Sponsor: Institute of Hematology & Blood Diseases Hospital, China

New P3 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3

Tolerability and Outcomes With Serial Cycles of 28 Days of Venetoclax in Newly Diagnosed Patients With Acute Myeloid Leukemia. (PubMed, Am J Hematol) - "The standard of care for newly-diagnosed unfit patients with acute myeloid leukemia (AML) is venetoclax (VEN) with azacitidine (AZA). Hematologic toxicities improved with subsequent cycles. Serial cycles with 28 days of VEN can be administered pre- and postremission with higher early myelosuppression but similar transfusion and infection rates compared to studies of reduced VEN duration."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Thrombocytopenia