Efficacy and safety of pivekimab sunirine (PVEK) in patients (pts) with blastic plasmacytoid dendritic cell neoplasm (BPDCN) in the CADENZA study.

6502 Background: BPDCN is a rare, clinically aggressive hematological malignancy primarily involving the skin, bone marrow, and lymph nodes. CD123 (IL-3Rα) is highly overexpressed on the surface of all BPDCN blasts making it an ideal target for novel immunochemotherapy. PVEK is a first-in-class antibody-drug conjugate comprising a high-affinity CD123 antibody, cleavable linker, and an indolinobenzodiazepine pseudodimer payload. Here, we present the primary analysis of efficacy and safety from CADENZA. Methods: In the open-label, multicenter, phase 1/2 CADENZA study, adults with BPDCN received PVEK monotherapy intravenously on day 1 of a 21-day cycle, as a <30-min outpatient infusion. Primary endpoint was the rate of composite complete response, defined as complete response (CR) + clinical CR (CR with minimal skin abnormality [CRc]) in frontline (1L) pts. Key secondary endpoints were duration of CR + CRc, median overall survival (OS), overall response rate (ORR), % of pts who were bridged to stem cell transplantation (SCT) after PVEK, and safety and tolerability. Results: At primary analysis (data cutoff: October 2, 2024), CADENZA enrolled 84 pts with CD123-positive BPDCN who received PVEK at the recommended phase 2 dose (RP2D) of 0.045 mg/kg every 21 days, including 33 pts with 1L BPDCN (median age, 73.0 [range, 48-84]; ≥65 years, 91%; male, 82%) and 51 pts with relapsed/refractory (R/R) BPDCN (median age, 69.0 [range, 19-85]; ≥65 years, 59%; male, 82%). Pts with R/R BPDCN had received 1-3 prior systemic therapies; 57% had prior tagraxofusp. Median follow-up was 21.5 mo for 1L pts and 24.1 mo for the R/R group. Among 1L pts, CR + CRc was 70% (95% CI, 51.3-84.4) and median duration of CR + CRc was 9.8 months (mo) (95% CI, 4.6-Not Reached [NR]); ORR was 85%. Median OS was 16.6 mo (95% CI, 11.4-NR). Among 13 (39%) 1L pts bridged to SCT, CR + CRc was 92% (95% CI, 64.0-99.8) and median OS was NR. In the R/R group, CR + CRc was 14% and median duration of CR + CRc was 9.2 mo (95% CI, 2.4-NR); ORR was 35%. Median OS was 5.8 mo (95% CI, 3.9-8.4) and 12% of pts bridged to SCT. Median (IQR) PVEK treatment exposure was 5 (4-9) cycles for the 1L group and 3 (2-5) cycles for the R/R group. Safety was assessed in all 84 pts. The most common treatment-emergent adverse event (TEAE) was peripheral edema (any grade, 54%; grade ≥3, 12%). TEAEs led to discontinuation in 9% and 7% of pts with 1L and R/R BPDCN, respectively. No capillary leak syndrome (CLS) events or treatment-related deaths were reported, and 2 (2%) pts experienced veno-occlusive disease of grades 2 and 3 after cycles 4 and 8, respectively, which resolved. Conclusions: PVEK treatment demonstrated promising efficacy, with high and durable CR + CRc responses. PVEK was tolerable at the RP2D. The safety profile was manageable, with no CLS events. These results support PVEK as a potential new treatment option for adult pts with BPDCN. Clinical trial information: NCT03386513 .