Elzonris (tagraxofusp-erzs)

P2, N=33, Recruiting, French Innovative Leukemia Organisation | Not yet recruiting --> Recruiting | Trial primary completion date: Jan 2026 --> Dec 2028

P1, N=7, Terminated, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | N=36 --> 7 | Trial completion date: Dec 2028 --> Jul 2025 | Active, not recruiting --> Terminated; Upon analysis of the first 7 participants accrued, it was determined that this combination treatment is not efficacious as treatment for patients with relapsed or refractory AML

Long-term survival appears strongly influenced by successful bridging to HSCT. Evidence remains predominantly non-randomized, underscoring the need for comparative and combination studies.

Key Messages: Shared care is particularly suitable for tagraxofusp treatment, as adverse events can be grade 3 or greater, but typically only occur in cycle 1, if they are to occur at all. Based on clinical experience, this article discusses the application of a shared-care model for tagraxofusp treatment in BPDCN.

P1, N=20, Recruiting, University of Kansas Medical Center | Not yet recruiting --> Recruiting

P2, N=53, Recruiting, Joshua Zeidner | Trial completion date: Dec 2027 --> Jul 2031 | Trial primary completion date: Aug 2027 --> Jul 2030

P1/2, N=31, Recruiting, Jacqueline Garcia, MD | Trial completion date: Dec 2028 --> Dec 2030 | Trial primary completion date: Dec 2026 --> Dec 2028

P1/2, N=64, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | Trial completion date: Jan 2026 --> Jan 2027 | Trial primary completion date: Jan 2026 --> Jan 2027

To our knowledge, this is the first reported case demonstrating the use of tagraxofusp in a patient with BPDCN and advanced chronic kidney disease, showing that even a minimum of tolerated treatment dose can induce a sustained response. Despite the risk of adverse events, tagraxofusp should be considered a viable treatment option for elderly patients with poor performance status and significant comorbidities who are ineligible for intensive chemotherapy or stem cell transplantation, as even limited exposure may achieve meaningful clinical responses.

Common adverse events included increased alanine aminotransferase (81.8%) and aspartate aminotransferase (72.7%), hypoalbuminemia, hypokalemia, and capillary leak syndrome (54.5%). The results indicate that TAG was effective and had a manageable safety profile in Japanese BPDCN patients.

These findings demonstrate the on-target effect and unique BM-sparing profile of tagraxofusp, which are paramount when treating myelosuppressive, CD123-positive hematologic diseases. The results support single-agent tagraxofusp as standard-of-care, nonmyelosuppressive first-line treatment for BPDCN and as a potential combination partner for other CD123-positive hematologic malignancies.

The approval of tagraxofusp established a foundation for targeted therapy in BPDCN and demonstrated high response rates, leading to the development of additional antibody - drug conjugates and cellular therapies targeting CD123. Other promising targeted approaches include BCL2 inhibitors, proteasome inhibitors, and therapies directed against surface antigens such as CD38 and CD303, as well as bromodomain and extraterminal (BET) inhibitors. Collectively, these strategies represent important advances that may significantly improve the historically poor outcomes associated with BPDCN.