A novel antibody-drug conjugate has demonstrated remarkable efficacy in treating blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare and aggressive blood cancer, according to results from a Phase I/II clinical trial presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.
The first-in-class therapy, pivekimab sunirine (PVEK), achieved an overall response rate of 85% and complete response rate of 70% as frontline treatment in newly diagnosed BPDCN patients, with a median overall survival of 16.6 months.
Targeting an Aggressive Rare Cancer
BPDCN is an exceedingly aggressive and uncommon blood cancer characterized by malignant involvement of the bone marrow, skin, and occasionally lymph nodes. The therapeutic landscape for BPDCN has historically been limited, with patients facing poor prognosis and resistance to conventional chemotherapy.
"Patients with BPDCN are in need of improved frontline therapies to treat their disease, so we're very excited to see this trial going extremely well in terms of safety and efficacy," said Dr. Naveen Pemmaraju, professor of Leukemia at The University of Texas MD Anderson Cancer Center, who led the trial together with Dr. Naval Daver. "The responses we have observed make PVEK a strong candidate as a standard-of-care treatment."
Precision Targeting Through CD123
PVEK functions through precision targeting of CD123, a receptor highly expressed on BPDCN cells. As an antibody-drug conjugate, it works by coupling a monoclonal antibody to a potent cytotoxic agent via a chemical linker, selectively delivering its therapeutic payload to malignant cells while minimizing systemic toxicity.
The antibody component specifically recognizes the CD123 antigen, facilitating internalization. Once internalized, the conjugated payload induces targeted cytotoxicity through DNA damage or disruption of microtubule dynamics, depending on the payload's nature. This precise delivery system mitigates collateral damage to non-malignant cells, a limitation inherent to conventional chemotherapeutics.
CADENZA Trial Results
The global multi-center CADENZA trial enrolled 84 adult patients with CD123-positive BPDCN across multiple centers. The study included 33 newly diagnosed patients and 51 patients with relapsed or refractory disease who had undergone one to three prior lines of therapy.
Participants received PVEK intravenously on day one of a 21-day cycle in an outpatient setting. Within the frontline treatment arm, the 33 newly diagnosed BPDCN patients demonstrated the most striking response rates, with 85% overall response rate and 70% achieving complete remission.
Favorable Safety Profile
The compelling efficacy data are complemented by PVEK's manageable safety profile. The most commonly observed adverse event was peripheral edema, which was reversible and clinically manageable. This contrasts favorably with the current standard of care, tagraxofusp-erzs, which targets the same CD123 receptor but carries a distinct toxicity spectrum including capillary leak syndrome.
MD Anderson researchers previously helped advance tagraxofusp-erzs toward FDA approval in 2018, making PVEK a next-generation CD123-targeted treatment that builds upon this foundation.
Future Therapeutic Potential
The success of PVEK aligns with the broader oncology trend embracing precision medicine. By exploiting tumor-specific surface markers, ADCs like PVEK herald an era where targeted cytotoxic delivery can surmount the challenges posed by heterogeneity and drug resistance characteristic of malignancies like BPDCN.
Given the promising results, researchers see potential for investigating combination therapies of PVEK with other treatments active in BPDCN in future clinical trials. The modular nature of ADC design allows for strategic combination with other immunomodulatory or cytotoxic agents, an avenue currently under consideration for future clinical exploration.
The clinical trial was funded by AbbVie, reflecting the collaborative effort between academic research and pharmaceutical innovation in developing targeted therapies for rare cancers.
