ASH 2025 | Pivekimab sunirine + Ven + Aza in unfit patients with ND CD123+ AML: Phase Ib/II efficacy and safety

Following the 67th American Society of Hematology (ASH) Annual Meeting and Exposition, December 6–9, 2025, Orlando, US, the AML Hub was pleased to speak with Gail Roboz, Weill Cornell Medicine, New York, US. We asked, What are the latest findings from clinical trials of pivekimab sunirine in unfit patients with newly diagnosed (ND) acute myeloid leukemia (AML)?

In this interview, Roboz discusses key findings from a preliminary subgroup analysis of a phase Ib/II trial (NCT04086264), investigating outcomes with the anti-CD123 antibody–drug conjugate pivekimab sunirine (PVEK), in combination with venetoclax (Ven), for ≥14 days (Cohort 1) or 28 days (Cohort 2), and azacitidine (Aza) on Days 1–7, in unfit patients with ND CD123+ AML. The primary endpoint was antileukemic activity, including complete remission (CR) and composite CR with incomplete hematologic recovery (CR/CRi) rates.

Key points

• The trial enrolled patients (N = 76) with ND CD123+ AML aged ≥18 years with Eastern Cooperative Oncology Group performance status (ECOG PS) score ≤1. The subgroup analysis included patients aged ≥75 years, or <75 years with ECOG PS score of 2–3 or with ≥1 defined comorbidity (N = 49).
• The majority of patients were categorized as having intermediate- (20%) or adverse-risk (51%) AML. TP53 mutations were present in 35% of patients.
• Overall, CR was achieved in 63% of patients receiving PVEK + Aza + Ven, with a median duration of CR of 16.1 months, while CR/CRi was achieved in 80% of patients.
• CR was achieved in 50% of patients receiving PVEK + Aza + Ven in Cohort 1 (n = 10) and in 67% of patients in Cohort 2 (n = 39). The CR/CRi rates with PVEK + Aza + Ven in Cohorts 1 and 2 were 70% and 82%, respectively.
• High rates of MRD negativity were observed in patients who achieved CR (Cohort 1, 80%; Cohort 2, 95%) and CR/CRi (Cohort 1, 83%; Cohort 2, 92%).
• At a median follow-up of 16.2 months, median overall survival was 12.4 months overall, 8.5 months in patients with TP53 mutations, and not reached in those with wild-type TP53.
• The triplet regimen was well tolerated in this population, with no new safety signals identified.
  • The most common treatment-emergent hematologic adverse events (AEs) of any grade were neutropenia (74%) and thrombocytopenia (67%), and the most common treatment-emergent non-hematologic AEs of any grade were constipation (61%) and peripheral edema (53%).
  • The primary reasons for discontinuation of PVEK were AEs, in 8% of patients, and disease progression or stem cell transplant. No veno-occlusive disease of any grade was observed.
• Data demonstrated promising and durable efficacy and safety of PVEK + Ven + Aza in unfit patients with ND AML, suggesting further investigation of the regimen in a randomized trial is worthwhile.

This educational resource is independently supported by AbbVie. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence on the content of this resource.