Elzonris (tagraxofusp-erzs) / Menarini, Nippon Shinyaku - LARVOL DELTA

Efficacy and safety of pivekimab sunirine (PVEK) in patients (pts) with blastic plasmacytoid dendritic cell neoplasm (BPDCN) in the CADENZA study. (ASCO 2025) - P1/2 | "Pts with R/R BPDCN had received 1-3 prior systemic therapies; 57% had prior tagraxofusp. PVEK treatment demonstrated promising efficacy, with high and durable CR + CRc responses. PVEK was tolerable at the RP2D. The safety profile was manageable, with no CLS events."

Clinical • Hematological Malignancies • Hepatology • Oncology • CD123 • IL3RA

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

First-line tagraxofusp induces durable responses with prolonged survival in adults younger than 50 years with blastic plasmacytoid dendritic cell neoplasm: Post hoc analysis of a phase 2 trial. (PubMed, Br J Haematol) - No abstract available

Journal • P2 data • Retrospective data • Oncology • Transplantation

A Multi-Site Break Through Cancer Trial: Targeting Measurable Residual Disease in Patients With Acute Myeloid Leukemia: A Phase 1/2 Study of Tagraxofusp, Azacitidine, and Venetoclax (clinicaltrials.gov) - P1/2 | N=31 | Recruiting | Sponsor: Jacqueline Garcia, MD | Trial completion date: Dec 2028 ➔ Dec 2030 | Trial primary completion date: Dec 2026 ➔ Dec 2028

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Neutropenia • Oncology • IL3RA

EFFICACY AND SAFETY OF PIVEKIMAB SUNIRINE (PVEK) IN PATIENTS (PTS) WITH BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM (BPDCN) IN THE CADENZA STUDY (EHA 2025) - P1/2 | "Pts with R/R BPDCN had received 1-3 prior systemic therapies; 57% had prior tagraxofusp (TAG). PVEK treatment demonstrated promising efficacy, with high and durable CR + CRc responses, and was tolerable at the RP2D. The safety profile was manageable, with no CLS events, predominantly low-grade peripheral edema, and very low incidence of resolvable VOD, a potential TEAE important to monitor during treatment. These results support PVEK as a potential new treatment option for adult pts with BPDCN."

Clinical • Fatigue • Hematological Malignancies • Hepatology • Oncology • CD123 • IL3RA

Tagraxofusp after Transplant: A Phase I Safety Study of Post-HCT Maintenance in CD123+ Myeloid Malignancies (TCT-ASTCT-CIBMTR 2026) - "Tagraxofusp is well tolerated post-transplant with no high-grade capillary leak, although the tolerated dose is lower than the FDA-approved regimen of 12 mcg/kg/day for 5 days. Enrollment at D1 is ongoing to define the maximum tolerated dose, and an expansion will assess efficacy and explore disease-specific outcomes. Future studies will evaluate combination regimens to enhance relapse prevention."

Clinical • P1 data • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Back Pain • Chronic Graft versus Host Disease • Chronic Myelomonocytic Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Musculoskeletal Pain • Myelodysplastic Syndrome • Myelofibrosis • Oncology • Pulmonary Disease • Thrombocytopenia • Transplantation • CD123 • IL3RA

Results of a Phase I/II Study of Tagraxofusp in Combination with Decitabine for Patients with Myelodysplastic/Myeloproliferative Neoplasms and Higher Risk Myelodysplastic Syndromes (ASH 2024) - "One patient (11%) had received prior allogeneic stem-cell transplantation and 1 (11%) had received prior HMA-venetoclax therapy...Both events occurred in patients >75 years of age during cycle 1 of therapy and reverted to baseline (< grade 1) with appropriate management including steroids, albumin and furosemide. One patient received a single dose of tocilizumab...Although TAG at low doses is associated with acceptable safety profile with no new safety signals, CLS and CRS can be observed in older patients. Further follow up and enrollment is ongoing in younger (<75 years of age) patients to confirm the long-term efficacy and safety of this combination."

Clinical • Combination therapy • P1/2 data • Atrial Fibrillation • Cardiovascular • Chronic Myelomonocytic Leukemia • Constipation • Cough • Febrile Neutropenia • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • CD123 • IL3RA • TP53

Phase 1b trial of tagraxofusp in combination with azacitidine with or without venetoclax in acute myeloid leukemia. (PubMed, Blood Adv) - "Median overall survival and progression-free survival were 14 months (95% CI, 9.5-NA) and 8.5 months (95% CI, 5.1-NA), respectively. In summary, TAG-AZA-VEN shows encouraging safety and activity in high-risk AML, including TP53-mutated disease, supporting further clinical development of TAG combinations."

Combination therapy • IO biomarker • Journal • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Oncology • CD123 • IL3RA • TP53

GSK plc...announced that China’s National Medical Products Administration (NMPA) has approved a new indication for Trelegy Ellipta (fluticasone furoate / umeclidinium / vilanterol ‘FF/UMEC/VI’) for the treatment of patients with asthma aged 18 years and older, adding to its current license for use in patients with chronic obstructive pulmonary disease (COPD). (GSK Press Release) - "The approval means that FF/UMEC/VI is the first and only single inhaler triple therapy (SITT) approved for the maintenance treatment of both respiratory conditions in the country. Approval was based on GSK’s CAPTAIN study which showed that in patients uncontrolled on inhaled corticosteroids/long-acting beta agonist (ICS/LABA), the additional bronchodilation provided by FF/UMEC/VI demonstrated significant improvements in lung function compared with FF/VI."

China approval • Asthma • Immunology

Phase I/II Study of Tagraxofusp in Combination With Decitabine for Patients With Myelomonocytic/Myeloproliferative Neoplasm and High Risk Myelodysplastic Syndromes (clinicaltrials.gov) - P1/2 | N=64 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Recruiting ➔ Active, not recruiting | Trial completion date: Jan 2026 ➔ Jan 2027 | Trial primary completion date: Jan 2026 ➔ Jan 2027

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

Efficacy of first-line tagraxofusp in blastic plasmacytoid dendritic cell neoplasm with prior or concomitant hematologic malignancy: subgroup analysis of a pivotal trial. (PubMed, Leuk Lymphoma) - No abstract available

Journal • Hematological Disorders • Hematological Malignancies • Oncology

Subgroup analysis by fitness criteria of patients (pts) with blastic plasmacytoid dendritic cell neoplasm (BPDCN) treated with first-line (1L) tagraxofusp (TAG). (ASCO 2025) - P1/2 | "1L TAG BPDCN treatment yielded high response rates regardless of HCT-CI fitness, with a similar safety profile across HCT-CI groups. TAG enabled bridge to HCT across all fitness groups, including pts with high risk possibly ineligible for IC, as TAG is not associated with prolonged myelosuppression seen with IC. These results affirm TAG as the SOC in 1L treatment for the majority of pts with BPDCN."

Clinical • Hematological Disorders • Hematological Malignancies • Oncology • Thrombocytopenia • CD123 • IL3RA

Characteristics and Outcomes of Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm Treated with Frontline HCVAD. (PubMed, Blood Adv) - "In this setting, we sought to analyze outcomes of the cytotoxic chemotherapy backbone regimen hyperfractionated cyclophosphamide, vincristine, adriamycin, and dexamethasone (HCVAD) in BPDCN. We conducted a retrospective analysis of patients with BPDCN (n=100), evaluating complete remission (CR) and median overall survival (OS) among three groups: those who received frontline HCVAD-based (n=35) vs SL-401 (n=37) vs other regimens (n=28)...These results suggest a continued important role for HCVAD-based chemotherapy for BPDCN, even in the modern targeted-therapy era, with high CR rates in the frontline setting. Further studies must establish the clinical activity, feasibility, and safety, of doublet/triplet combinations of targeted therapies plus cytotoxic agents and addition of CNS prophylaxis, with ultimate goal of durable long-term remissions for patients with BPDCN."

Journal • Bone Marrow Transplantation • Hematological Malignancies • Oncology • Transplantation • BCL2 • CD123

Tagraxofusp in Blastic Plasmacytoid Dendritic-Cell Neoplasm. (PubMed, N Engl J Med) - P1/2; "In adult patients with untreated or relapsed BPDCN, the use of tagraxofusp led to clinical responses. Serious adverse events included capillary leak syndrome; hepatic dysfunction and thrombocytopenia were common. (Funded by Stemline Therapeutics and the Leukemia and Lymphoma Society Therapy Acceleration Program; ClinicalTrials.gov number, NCT02113982.)."

Journal • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Oncology • Transplantation

Long-Term Benefits of Tagraxofusp for Patients With Blastic Plasmacytoid Dendritic Cell Neoplasm. (PubMed, J Clin Oncol) - "In first-line patients with BPDCN, TAG monotherapy resulted in high and durable responses, allowing many to bridge to stem-cell transplant. TAG was generally well-tolerated with a predictable and manageable safety profile."

Journal • Bone Marrow Transplantation • Hematological Malignancies • Oncology • Transplantation • CD123

INTERIM ANALYSIS OF A REGISTRATION ENABLING STUDY OF PIVEKIMAB SUNIRINE (PVEK, IMGN632) A CD123-TARGETING ANTIBODY-DRUG CONJUGATE, IN PATIENTS WITH BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM (BPDCN) (EHA 2023) - P1/2 | "BPDCN currently has 1 approved therapy, tagraxofusp (TAG), with a median age of 68, CR/CRc rate of 57% and mOS of 15.8 mos (n=65; Pemmaraju JCO 2022). PVEK demonstrates compelling activity in frontline and R/R BPDCN pts, including durable responses in the R/R setting for pts who received prior TAG. PVEK safety was manageable with primarily low-grade IRRs and edema and no new safety signals were observed. Enrollment continues in the pivotal de novo frontline BPDCN cohort (NCT03386513) Antibody targeting, Monoclonal antibody, Myeloid malignancies"

Clinical • Chronic Myelomonocytic Leukemia • Constipation • Fatigue • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Neutropenia • Oncology • Thrombocytopenia • Transplantation • CD123

Relapsing Blastic Plasmacytoid Dendritic Cell Neoplasm With Neurologic Involvement. (PubMed, Cureus) - "She achieved initial remission after AML-type induction chemotherapy (7+3 with cytarabine and idarubicin) but was lost to follow-up and received no consolidation therapy...She was treated with intrathecal chemotherapy and systemic daunorubicin/vincristine but demonstrated refractory disease and developed diffuse alveolar hemorrhage with cytologic confirmation of pulmonary BPDCN involvement. Given the aggressive relapse and complications, she is being transitioned to targeted therapy with tagraxofusp, with plans for eventual allogeneic stem cell transplantation pending clinical stability. This case highlights the fulminant course of relapsed BPDCN in a young patient, the limitations of conventional chemotherapy, and the urgent need for early consideration of novel targeted therapies. Recognition of atypical manifestations, including ocular and pulmonary involvement, is essential to guide timely diagnosis and management."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Musculoskeletal Pain • Oncology • Pain • Transplantation

First-line tagraxofusp leads to durable responses and prolonged survival in adults with blastic plasmacytoid dendritic cell neoplasm regardless of fitness level. (PubMed, Haematologica) - "Not available."

Journal • Oncology

Sustained response to minimal-dose tagraxofusp in a patient with BPDCN and advanced chronic kidney disease. (PubMed, Ann Hematol) - "To our knowledge, this is the first reported case demonstrating the use of tagraxofusp in a patient with BPDCN and advanced chronic kidney disease, showing that even a minimum of tolerated treatment dose can induce a sustained response. Despite the risk of adverse events, tagraxofusp should be considered a viable treatment option for elderly patients with poor performance status and significant comorbidities who are ineligible for intensive chemotherapy or stem cell transplantation, as even limited exposure may achieve meaningful clinical responses."

Journal • Cardiovascular • Chronic Kidney Disease • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Nephrology • Oncology • Renal Disease • Transplantation • CD123 • IL3RA • KRAS • TET2 • ZRSR2

PMDA regulatory update on approval and revision of the precautions for use of anticancer drugs in Japan; imlunestrant for breast cancer, tafasitamab for follicular lymphoma, atezolizumab for thymic carcinoma, retifanlimab for anal canal squamous cell carcinoma, and tagraxofusp for blastic plasmacytoid dendritic cell neoplasm. (PubMed, Int J Clin Oncol) - No abstract available

Japanese regulatory • Journal • Anal Carcinoma • Breast Cancer • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Thymic Carcinoma • Thymus Cancer

A phase I/II study of tagraxofusp in Japanese patients with blastic plasmacytoid dendritic cell neoplasm. (PubMed, Int J Hematol) - "Common adverse events included increased alanine aminotransferase (81.8%) and aspartate aminotransferase (72.7%), hypoalbuminemia, hypokalemia, and capillary leak syndrome (54.5%). The results indicate that TAG was effective and had a manageable safety profile in Japanese BPDCN patients."

Journal • P1/2 data • Hematological Disorders • Hematological Malignancies • Infectious Disease • Oncology • CD123 • IL3RA

Hematopoietic effects of tagraxofusp in treatment-naive patients with blastic plasmacytoid dendritic cell neoplasm. (PubMed, Cancer) - P1/2 | "These findings demonstrate the on-target effect and unique BM-sparing profile of tagraxofusp, which are paramount when treating myelosuppressive, CD123-positive hematologic diseases. The results support single-agent tagraxofusp as standard-of-care, nonmyelosuppressive first-line treatment for BPDCN and as a potential combination partner for other CD123-positive hematologic malignancies."

Journal • Hematological Disorders • Hematological Malignancies • Neutropenia • Oncology • Thrombocytopenia • CD123 • IL3RA

The role of targeted therapies in blastic plasmacytoid dendritic cell neoplasm. (PubMed, Expert Opin Biol Ther) - "The approval of tagraxofusp established a foundation for targeted therapy in BPDCN and demonstrated high response rates, leading to the development of additional antibody - drug conjugates and cellular therapies targeting CD123. Other promising targeted approaches include BCL2 inhibitors, proteasome inhibitors, and therapies directed against surface antigens such as CD38 and CD303, as well as bromodomain and extraterminal (BET) inhibitors. Collectively, these strategies represent important advances that may significantly improve the historically poor outcomes associated with BPDCN."

Journal • Review • Bone Marrow Transplantation • Oncology • Transplantation • CD123 • CLEC4C • IL3RA

Use of alternative components to facilitate timely administration of tagraxofusp. (PubMed, J Oncol Pharm Pract) - No abstract available

Journal

Current status and future potential of CD123-based targeted therapies for acute leukemia. (PubMed, Expert Opin Biol Ther) - "It discusses completed and ongoing clinical trials for agents such as tagraxofusp, pivekimab sunirine, flotetuzumab, vibecotamab, and investigational CAR T-cell therapies (e.g. MB-102, UCART123v1.2). While clinical activity has been demonstrated, especially in BPDCN, therapeutic durability and safety remain hurdles. Precision in antigen targeting, combination strategies, and toxicity management will be critical for successful integration of CD123-directed therapies into standard clinical practice."

Journal • Review • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • CD123 • IL3RA