FDA Receives BLA Submission for the Approval of Pivekimab Sunirine for BPDCN

A biologics license application (BLA) has been submitted to the FDA seeking the approval of pivekimab sunirine (IMGN632), an investigational antibody-drug conjugate (ADC) being developed for the treatment of patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN).1

The BLA submission is based on findings from the phase 1/2 CADENZA trial (NCT03386513), which demonstrated that among patients with first-line de novo disease (n = 20), the composite complete response (cCR) rate reached 75% (95% CI, 50.9%-91.3%), meeting the trial’s primary end point.2 The overall response rate (ORR) in this group was 80% (95% CI, 56.3%-94.3%). Across all patients treated in the first-line setting, including those with de novo or prior/concomitant hematologic malignancies (n = 33), the cCR rate was 70% (95% CI, 51.3%-84.4%), and the ORR was 85% (95% CI, 68.1%-94.9%). Among relapsed/refractory patients (n = 51), the activity of the ADC was more modest, with a cCR rate of 14% (95% CI, 5.7%-26.3%) and an ORR of 35% (95% CI, 22.4%-49.9%).

“Meaningful innovations in cancer research and treatment are happening every day. It is important that these innovations reach patients who desperately need them, including those with rare cancers who have limited options,” Roopal Thakkar, executive vice president of research and development and chief scientific officer at AbbVie, explained in a news release.1 “We look forward to the next steps in the regulatory process for our latest ADC, our first ADC in blood cancer, and how it may advance treatment for those living with BPDCN.”

What Was the Design of the CADENZA Trial of Pivekimab Sunirine in Hematologic Malignancies?

The CADENZA trial is a nonrandomized, open-label, multicenter study designed to evaluate pivekimab sunirine in patients with CD123-positive hematologic malignancies, including blastic plasmacytoid dendritic cell neoplasm (BPDCN).2

Eligible patients were required to be 18 years or older, have an ECOG performance status of 0 or 1, and demonstrate adequate organ function and liver enzyme levels. Patients with a history of hepatic veno-occlusive disease, grade 4 capillary-leak syndrome, noncardiac grade 4 edema, or central nervous system disease (for first-line patients), were excluded.

Two primary patient cohorts were enrolled:

• First-line BPDCN (no prior systemic therapy): This cohort included patients with de novo BPDCN and those with BPDCN with prior or concomitant hematologic malignancy. De novo patients represented the primary analysis population.
• Relapsed/refractory BPDCN: This cohort included patients with a history of 1 to 3 prior systemic therapies.

All patients received pivekimab sunirine intravenously via infusion lasting less than 30 minutes on day 1 of each 21-day cycle. The RP2D was established as 0.045 mg/kg.

The primary end point was the rate of cCR, defined as morphologic CR plus clinical CR with minimal skin abnormality, in first-line patients with de novo BPDCN.

The key secondary end point was the duration of cCR in the first-line de novo population. Additional secondary end points were the cCR rate, time to cCR, ORR, OS, the proportion of patients successfully bridged to posttreatment stem cell transplantation, and the frequency and severity of adverse effects (AEs).

What Were the Safety Findings From the CADENZA Trial of Pivekimab Sunirine in BPDCN?

Nonhematologic AEs that were reported in at least 15% of patients included peripheral edema, infusion-related reactions, fatigue, nausea, diarrhea, constipation, and hypokalemia. Peripheral edema was common across groups, affecting 65% of first-line de novo patients, 73% of all first-line patients, and 41% of relapsed/refractory patients. Infusion-related reactions occurred in 10% of first-line de novo patients, 9% of all first-line patients, and 37% of relapsed/refractory patients, despite the use of prophylactic premedications. Fatigue was reported in 24% to 30% of patients, and gastrointestinal toxicities like nausea, diarrhea, and constipation occurred in 15% to 25% of patients. Hypokalemia was observed in 14% to 30% of patients. Headache (10%-40% of patients) and hypoalbuminemia (12%-21% of patients) were also noted.

Serious AEs were reported in 51% of patients, most commonly COVID-19 infection, generalized edema, pneumonia, pneumonitis, and febrile neutropenia. Grade 3 or higher AEs occurred in 79% of patients, with neutropenia, thrombocytopenia, peripheral edema, pneumonitis, and pneumonia occurring in at least 10% of patients. For example, grade 3 or higher thrombocytopenia occurred in 24% of all first-line patients and all relapsed/refractory patients, and grade 3 or higher neutropenia was reported in up to 16% of patients. Importantly, no cases of capillary-leak syndrome were reported.

References

1. AbbVie submits biologics license application (BLA) to U.S. FDA for pivekimab sunirine (PVEK) - an investigational antibody-drug conjugate (ADC) to treat rare cancer with limited treatment options. News release. AbbVie. September 30, 2025. Accessed September 30, 2025. https://news.abbvie.com/2025-09-30-AbbVie-Submits-Biologics-License-Application-BLA-to-U-S-FDA-for-Pivekimab-sunirine-PVEK-an-Investigational-Antibody-Drug-Conjugate-ADC-to-Treat-Rare-Cancer-with-Limited-Treatment-Options
2. Pemmaraju N, Marconi G, Montesinos P, et al. Efficacy and safety of pivekimab sunirine (PVEK) in patients (pts) with blastic plasmacytoid dendritic cell neoplasm (BPDCN) in the CADENZA study. J Clinl Oncol. 2025;43(16_suppl):6502-6502. doi:10.1200/jco.2025.43.16_suppl.6502