Combination treatment with pivekimab sunirine, azacitidine, and venetoclax has demonstrated activity in patients with relapsed/refractory or newly diagnosed acute myeloid leukemia (AML), according to a presentation at the 2022 ASH Annual Meeting.

Pivekimab sunirine is an antibody-drug conjugate consisting of a high-affinity CD123 antibody, cleavable linker, and an indolinobenzodiazepine pseudodimer (IGN) payload, explained study presenter Naval Daver, MD, of The University of Texas MD Anderson Cancer Center in Houston.

The IGN payload alkylates DNA and causes single-strand breaks without crosslinking, which may cause less marrow toxicity than agents that induce double-strand DNA breaks, he added. 

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Dr Daver and colleagues conducted a phase 1b/2 study ( Identifier: NCT04086264) to evaluate pivekimab sunirine in combination with azacitidine and venetoclax in patients with newly diagnosed or relapsed/refractory, CD123-positive AML.

Results in Relapsed/Refractory AML

The 91 patients with relapsed/refractory AML had a median age of 67 (range, 25-83) years at baseline, 74% had de novo AML, 53% had adverse cytogenetics, 20% had RUNX1 mutations, 18% had TP53 mutations, and 14% had FLT3 mutations.

Patients received treatment in a 3-drug escalation over a 28-day cycle — pivekimab sunirine at 0.015 mg/kg or 0.045 mg/kg on day 7, azacitidine at 50 mg/kg2 or 75 mg/m2 on days 1-7, and venetoclax at 400 mg for 8, 14, or 21 days. 

The recommended phase 2 dosing schedule was pivekimab sunirine at 0.045 mg/kg on day 7, azacitidine at 75 mg/m2 on days 1-7, and venetoclax for 14 days.

The overall response rate (ORR) was 45%, the composite complete remission (CCR) rate was 25%, and the complete remission (CR) rate was 13%. Among patients who received the recommended phase 2 dose, the ORR was 38%, the CCR rate was 22%, and the CR rate was 14%.

The ORR was 53% among venetoclax-naïve patients and 36% among patients with prior venetoclax treatment. The CRR rate was 38% and 11%, respectively.

Overall, the median time to CCR was 1.1 month, and the median duration of CCR was 7.7 months.

The most common treatment-emergent adverse events were febrile neutropenia (33%), thrombocytopenia (23%), dyspnea (22%), infusion-related reactions (22%), hypokalemia (21%), and fatigue (20%). 

There were no cases of tumor lysis syndrome, veno-occlusive disease, capillary leak syndrome, or cytokine release syndrome. Five percent of patients discontinued treatment due to pivekimab sunirine-related adverse events, but there were no treatment-related deaths.

Results in Newly Diagnosed AML

The 10 patients with newly diagnosed AML had a median age of 74 (range, 62-83) years at baseline, 80% had de novo AML, 40% had adverse cytogenetics, 20% had TP53 mutations, 10% had FLT3-TKD, 10% had IDH2 mutations, and 10% had NPM1 mutations.

All patients were treated with the recommended phase 2 dosing schedule. 

Five patients achieved a CR, and 1 achieved a partial response. One patient with a TP53 mutation achieved a CR, as did 1 patient with FLT3-TKD

Five patients were still on treatment at last follow-up, 1 patient went on to transplant, and 1 patient died within 60 days.

Dr Daver noted that enrollment of newly diagnosed patients is ongoing, with 25 centers in the United States and Europe enrolling patients.  

Disclosures: This research was supported by ImmunoGen, Inc. and Jazz Pharmaceuticals. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Daver N, Montesinos P, Aribi A, et al. Broad activity for the pivekimab sunirine (PVEK, IMGN632), azacitidine, and venetoclax triplet in high-risk patients with relapsed/refractory acute myeloid leukemia (AML). Presented at ASH 2022. December 10-13, 2022. Abstract 62.