FDA Receives BLA for Pivekimab Sunirine in Rare Hematologic Malignancy

Developers at AbbVie have submitted a biologics license application (BLA) to the FDA seeking the approval of pivekimab sunirine as a treatment for patients with blastic plasmacytoid dendritic cell neoplasms (BPDCN), according to a press release from the developers.¹

BPDCN is a rare, aggressive blood cancer with features that bear resemblance to lymphoma and leukemia. Those who have BPDCN typically present with skin lesions, with disease often spreading to the bone marrow, central nervous system, and lymph nodes. According to the developers, frontline therapeutic options for this population include intensive chemotherapy followed by stem cell transplant, necessitating additional treatment strategies for patients with newly diagnosed and relapsed/refractory disease.

Developers engineered pivekimab sunirine as an investigational CD123-directed antibody drug conjugate (ADC) for use in BPDCN and other hematologic malignancies like acute myeloid leukemia. Given the overexpression of CD123 in BPDCN, developers hypothesized that the protein would be an ideal therapeutic target in this population.

“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, stated in the press release.¹ “We look forward to 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.”

Supporting data for the BLA came from the phase 1/2 CADENZA trial (NCT03386513), in which investigators evaluated treatment with pivekimab sunirine monotherapy for patients with CD123-positive hematologic malignancies, including BPDCN. Investigators previously presented data from the CADENZA trial at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.²

Treatment with pivekimab sunirine produced a complete response (CR) and CR with minimal skin abnormality (CRc) rate of 75% (95% CI, 50.9%-91.3%) and an overall response rate (ORR) of 80% (95% CI, 56.3%-94.3%) among patients with frontline de novo BPDCN (n = 20). The respective rates were 70% (95% CI, 51.3%-84.4%) and 85% (95% CI, 68.1%-94.9%) for all patients in the frontline setting (n = 33), as well as 14% (95% CI, 5.7%-26.3%) and 35% (95% CI, 22.4%-49.9%) for those with relapsed/refractory disease (n = 51).

The median overall survival (OS) was 16.6 months (95% CI, 7.2-not reached [NR]) among patients with first-line de novo disease and 16.6 months (95% CI, 11.4-NR) among all patients in the first-line setting. Among those with relapsed/refractory disease, the study treatment produced a median OS of 5.8 months (95% CI, 3.9-8.4).

In the open-label, multicenter phase 1/2 CADENZA trial, investigators assessed 2 groups of patients with CD123-positive BPDCN. One group included those with no prior exposure to systemic therapy, which was comprised of those with de novo BPDCN in the primary analysis population and those with BPDCN and prior or concomitant hematologic malignancies. The second patient group included those with relapsed/refractory disease following 1 to 3 prior lines of systemic treatment.

All patients enrolled on the trial received pivekimab sunirine at the recommended phase 2 dose of 0.045 mg/kg on day 1 of each 21-day cycle.

The trial’s primary end point was the CRc rate among patients with first-line de novo disease. A key secondary end point was the duration of CR plus CRc in the frontline de novo group. Other secondary end points included the CR plus CRc rate, time to CR plus CRc rate, ORR, OS, and frequency and severity of adverse effects (AEs).

The most common hematologic AEs in the frontline de novo, entire first-line, and relapsed/refractory groups, respectively, included anemia (15%, 27%, 14%), neutropenia (0%, 15%, 18%), and thrombocytopenia (20%, 36%, 31%). AEs associated with dose delays, dose reductions, and treatment discontinuations occurred in 25.0%, 4.8%, and 13.1% of patients, respectively.

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://tinyurl.com/ykzujenf
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 Clin Oncol. 2025;43(suppl 16):6502. doi:10.1200/JCO.2025.43.16_suppl.6502