CHICAGO–Early results from the lead-in phase of an ongoing phase II trial of SL-401 show high rates of overall response and complete response in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), according to data presented at the 2016 ASCO Annual Meeting.
“BPDCN is a rare, aggressive hematologic malignancy of unmet medical need,” study author Naveen Pemmaraju, MD, from the University of Texas MD Anderson Cancer Center in Houston, Texas, explained during his presentation. SL-401 is a targeted therapy directed to the interleukin-3 receptor CD123, which is overexpressed in BPDCN, as well as other hematologic cancers.
This multi-center, phase II trial was designed to assess the efficacy of SL-401 in patients with BPDCN and relapsed/refractory acute myeloid leukemia (AML) in two stages:
- Lead-in (stage 1): Patients received SL-401 as a daily intravenous infusion at 7, 9, 12, or 16 ug/kg for up to 5 doses, repeated every 21 days, to determine the maximum tolerated dose (MTD)
- Expansion (stage 2): Patients received SL-401 at the optimal stage 1 dose
Stage 1 is completed, and the expansion stage is ongoing. At the data cut-off point (January 20, 2016), 18 patients with BPDCN (9 in each stage) were enrolled in the trial and received SL-401 treatment: three patients received 7 ug/kg (n=3; all in stage 1), and 15 received 12 ug/kg (6 in stage 1; 9 in stage 2). The median patient age was 70 years (range = 45-82 years).
SL-401 12 ug/kg was the maximum tested/recommended dose for patients with BPDCN and the MTD in patients with relapsed/refractory AML; MTD was not reached in BPDCN.
Among the 15 evaluable BPDCN patients, 87 percent (n=13) responded, with marked disease reductions in skin, bone marrow, lymph node, and viscera. The overall response rate (ORR) was 100 percent when SL-401 was used as front-line treatment (n=10/10) and 60 percent when it was used in the relapsed/refractory setting (n=3/5).
Of the eight previously untreated patients, SL-401 12 ug/kg led to complete responses (CR) in five patients and clinical CR (defined as CR in bone marrow, peripheral blood, lymph nodes, and spleen/liver or skin with gross clearance of all lesions from baseline) in three patients.
Six of those eight patients remain on SL-401 therapy while in remission (n=4) or were successfully bridged to hematopoietic cell transplantation (n=2).
The most common treatment-related adverse events (AEs) included transient transaminase elevation (57%) and hypoalbuminemia (40%). Transient thrombocytopenia was also reported in 15 percent of patients. Two patients in stage 1 had capillary leak syndrome (CLS), occurring as a grade 5 AE at the 7 ug/kg dose and as a grade 4 AE at the 12 ug/kg dose. Since these findings, safety precautions have been implemented to minimize the risk of severe CLS, which has not occurred at doses up to 12 ug/kg since the new precautions were implemented, according to the authors.
“SL-401 demonstrated robust single-agent activity in BPDCN, including 100 percent ORR in first-line, and 87 percent in all-lines, with multiple CRs,” Dr. Pemmaraju and authors concluded, however, results from this small study will need to be tested in larger patient populations. Response duration data are maturing, and results of SL-401 in the 30 patients with relapsed/refractory AML will be reported separately, they added.
Pemmaraju N, Lane AA, Sweet KL, et al. Results from phase 2 registration trial of SL-401 in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN): Lead-in completed, expansion stage ongoing. Abstract #7006. Presented at the 2016 American Society of Clinical Oncology Annual Meeting, Chicago, IL, June 4, 2016.