Data from the phase 2 CADENZA trial revealed front-line pivekimab sunirine to demonstrate clinical activity in patients with blastic plasmacytoid dendritic cell neoplasm.
Treatment with pivekimab sunirine (IMGN632) in the first-line elicited responses and showed favorable tolerability in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), according to updated data from the phase 2 CADENZA trial (NCT03386513).1
Findings revealed that of the 4 patients with de novo BPDCN treated with pivekimab, 2 achieved a complete response (CR) or a clinical CR. Among 6 patients with BPDCN who had a prior or concomitant hematologic malignancy (PCHM), 4 experienced a CR, clinical CR, or a CR with partial hematologic recovery. Additionally, 2 patients with de novo disease and 1 with PCHM who enrolled prior to the opening of the untreated cohort achieved a CR or clinical CR with pivekimab.
Pivekimab is a CD123-targeting antibody-drug conjugate currently in clinical development for patients with hematological malignancies, including BPDCN and acute myeloid leukemia. In October 2020, the FDA granted breakthrough therapy designation to pivekimab for the treatment of patients with relapsed/refractory BPDCN.
“We believe these initial frontline data from the CADENZA study further support the potential of pivekimab as an important treatment option for patients with BPDCN. Based on the initial frontline data observed to date, we will continue to explore the benefit of pivekimab in [patients with] de novo and PCHM [disease]. We look forward to sharing additional details of pivekimab in frontline BPDCN at an upcoming medical meeting,” said Anna Berkenblit, MD, senior vice president, and chief medical officer of ImmunoGen, in a press release.
CADENZA is an open-label, multi-center, phase 1/2 study looking to determine the maximum tolerated dose and assess the safety, tolerability, pharmacokinetics, immunogenicity, and antileukemia activity of pivekimab monotherapy in patients with BPDCN.2
Part 1 of the study was the dose-escalation portion where patients with relapsed/refractory acute myeloid leukemia or BPDCN were administered intravenous pivekimab on 2 different schedules.
Now, the study is enrolling in 2 BPDCN expansion cohorts at the recommended phase 2 dose.
The trial will continue to enroll patients aged 18 years and older with BPDCN with PCHM. Based on guidance from the FDA, which was provided in a recent Type B meeting, the company expects to enroll up to 20 patients with de novo BPDCN for inclusion in the efficacy analysis. As of now, 6 patients with de novo BPDCN have been enrolled.
Cohort 6 of the CADENZA trial is enrolling untreated patients with frontline BPDCN, including those with de novo disease and those with PCHM who have not received prior systemic therapy. However, patients may have received local therapy, such as radiotherapy, surgical excision, or photodynamic therapy. Additionally, patients with prior local therapy must have experienced recurrence or progression in the field of local therapy or disease outside the field of local therapy.
The primary end point of the study is CR and clinical CR with the key secondary end point of duration of CR and clinical CR. Other secondary end points include duration of overall response, overall response rate, overall survival, and safety.
Topline data regarding the primary and key secondary end points of the trial are expected to be released in 2024.
"With limited treatment options for this rare and aggressive cancer, I am encouraged by the data generated thus far for pivekimab in frontline BPDCN. BPDCN patients with PCHM are increasingly recognized as having significant unmet need as there are no therapies specific for this population,” said Kendra Sweet, MD, an associate member in the Department of Malignant Hematology at Moffitt Cancer Center, in the press release.