KEY TAKEAWAYS
- The phase 1/2 study determined the safety and anti-tumor activity of PVEK in frontline BPDCN patients and updated information on R/R BPDCN pts.
- PVEK demonstrated compelling activity and manageable safety in frontline and R/R BPDCN pts.
In this phase 1b/2 clinical trial, adult patients (pts) with frontline or relapsed/refractory blastic plasmacytoid dendritic cell neoplasm (BPDCN) were administered a 0.045 mg/kg intravenous dose of Pivekimab Sunirine (PVEK) on D1 of a 21-day treatment cycle, as a <30-min outpatient infusion.
As of September 14, 2022, data on the anti-tumor activity and safety are available for 58 pts with BPDCN; 16 frontline and 42 have relapsed or refractory (R/R) disease. The median age for frontline pts was 74 years, within a range of 60 to 80 years, and for R/R pts, it was 69 years, ranging from 19 to 83 years. Among frontline pts, 88% were 65 years or older.
Preliminary scans revealed that 76% had skin involvement, 50% had bone marrow (BM) abnormalities, and 43% showed nodal or visceral disease. Half of the frontline pts had concurrent or previous blood cancer, such as MDS or CMML. Among the 42 R/R pts, 33% had undergone a stem cell transplant, and 45% had previously been treated with tagraxofusp (TAG). The median number of PVEK doses administered overall was 3, but frontline pts received a median of 5 doses.
In terms of response, 81% of frontline pts showed an objective response rate (ORR), with 75% achieving a composite complete remission (CCR). One additional patient achieved complete remission (CR) post-transplant. All frontline pts with baseline BM involvement reported BM remissions. Twenty-five percent were transitioned to alloSCT. The median time to the first response was 1.5 months, and the median duration of response (DOR) for frontline pts was 10.7 months; seven remain on PVEK. For R/R pts, the ORR was 31%, and the composite complete remission rate was 19%. Among those who received prior TAG, the ORR was 26% and the CCR was 16%. The median DOR was 3.1 months; 10 pts remain on treatment.
The most frequent treatment-emergent adverse effects (TEAEs) included peripheral edema, thrombocytopenia, infusion reactions, constipation, fatigue, nausea, and neutropenia. No instances of cytokine release syndrome or capillary leak syndrome were reported. Only one patient experienced a grade 2 infusion-related reaction. Elevated liver enzyme levels were recorded in a small percentage, and one patient had a dose-limiting toxicity due to a grade 3 ALT increase. The 30-day mortality rate was 2%, with no deaths attributed to the treatment. One patient needed a dose reduction due to adverse events, and two discontinued PVEK for the same reason.
PVEK showed promising activity in frontline and R/R BPDCN pts, including durable responses in those who had previously been treated with TAG. The safety profile of PVEK was generally manageable, mainly featuring low-grade infusion-related reactions and edema, with no new safety concerns identified. The recruitment for the crucial study focusing on newly diagnosed BPDCN pts is still ongoing.
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03386513
Pemmaraju, N., Martinelli, G., Montesinos, P., Mazzarella, L., DeAngelo, D.J., Erba, H., Sweet, K., Walter, R., Deconinck, E., Legrand, O., Wang, E., Aribi, A., Ulrickson, M., Marconi, G., Lane, A., Kantarjian, H., Sloss, C., Malcolm, K., Zweidler-McKay, P., Daver, N. INTERIM ANALYSIS OF A REGISTRATION ENABLING STUDY OF PIVEKIMAB SUNIRINE (PVEK, IMGN632) A CD123-TARGETING ANTIBODY-DRUG CONJUGATE, IN PATIENTS WITH BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM (BPDCN).
