On June 9, 2023 ImmunoGen Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported updated data from an interim analysis of the Phase 2 CADENZA trial of pivekimab sunirine (pivekimab) in patients with frontline and relapsed/refractory (R/R) blastic plasmacytoid dendritic cell neoplasm (BPDCN) (Press release, ImmunoGen, JUN 9, 2023, View Source [SID1234632592]). The data will be presented in an oral session on Sunday, June 11 at the European Hematology Association (EHA) (Free EHA Whitepaper) 2023 Congress in Frankfurt, Germany.

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The CADENZA trial is enrolling frontline BPDCN patients, including those with de novo disease and those with a prior or concomitant hematologic malignancy (PCHM). As announced in August 2022, ImmunoGen aligned with the US Food and Drug Administration (FDA) that the efficacy analysis will be conducted in de novo BPDCN patients with CR/CRc as the primary endpoint. The secondary endpoint is duration of CR/CRc. With enrollment in the R/R cohort complete, ImmunoGen expects to complete enrollment in the pivotal frontline de novo cohort this year and report top-line data in 2024.

"BPDCN is a rare and aggressive blood cancer characterized by extremely low survival rates and limited treatment options that are often associated with significant toxicities," said Naveen Pemmaraju, MD, Associate Professor of Leukemia at The University of Texas MD Anderson Cancer Center and co-investigator of the Phase 2 study. "We are encouraged by these updated data in a larger population of patients, which demonstrated impressive anti-tumor activity and durable responses in both frontline and R/R patients. These efficacy data, coupled with outpatient administration, reinforce the potential of pivekimab as a promising, novel option for this challenging disease. I look forward to its continued evaluation in the trial."

INTERIM ANALYSIS OF A REGISTRATION-ENABLING STUDY OF PIVEKIMAB SUNIRINE, A CD123-TARGETING ANTIBODY-DRUG CONJUGATE, IN PATIENTS WITH BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM
Lead Author: Naveen Pemmaraju, MD
Presentation ID: S139
Session Date: Sunday, June 11
Session Time: 11:30am-12:45pm CEST / 5:30am-6:45am EDT

Pivekimab is administered at 0.045 mg/kg on day 1 of a 21-day cycle as an outpatient infusion of approximately 30 minutes. As of the May 19, 2023 data cutoff, data were available for 79 BPDCN patients (30 frontline, 49 R/R). Key interim and updated safety and efficacy findings include:

Efficacy

In frontline-treated patients including those with de novo and PCHM, the objective response rate (ORR [CR, CRc, CRh, CRi, PR]) is 80% (24/30 patients) with a composite complete remission (CCR [CR, CRc, CRh, CRi]) rate of 73% (22/30 patients), and an additional patient achieving a CR post-transplant.
Median duration of response (DOR) for all responders in frontline-treated patients was 12.7 months.
In R/R patients, the ORR was 33% (16/49 patients), with a CCR rate of 20% (10/49 patients), including those who previously failed intensive chemotherapy and/or transplant.
Median DOR for all responders in R/R patients was 7.1 months.
Safety

Pivekimab continues to exhibit manageable safety; no new safety signals were observed.
The most common treatment-emergent adverse events (TEAEs) (all grades [grade 3+ events]) occurring in 15% or more of patients were peripheral edema (46% [10%]), thrombocytopenia (27% [19%]), fatigue (25% [4%]),infusion-related reactions (25% [4%]), constipation (23% [0%]), nausea (22% [0%]) anemia (20% [8%]), headache (19% [4%]), neutropenia (18% [17%]), diarrhea (17% [0%]), hypokalemia (17% [3%]), dyspnea (15% [1%]), hyperglycemia (15% [6%]) and pyrexia (15% [1%]).
No capillary leak syndrome or cytokine release syndrome are reported.
Discontinuations due to pivekimab-related adverse events are 3%.
30-day mortality is 0% in frontline-treated patients and 4% (2 deaths due to disease progression) in R/R patients.
"We look forward to completing enrollment in CADENZA this year and are pleased with the interim data in frontline BPDCN, particularly the 73% CCR rate observed in this population, as well as the responses seen in those patients with more advanced R/R disease," said Anna Berkenblit, MD, Senior Vice President and Chief Medical Officer of ImmunoGen. "With promising anti-tumor activity, manageable safety including no observed capillary leak or cytokine release syndrome, and the convenience of potential outpatient administration, we believe pivekimab could serve as a critical option for BPDCN patients."

Additional information can be found at www.ehaweb.org.

ABOUT PIVEKIMAB SUNIRINE

Pivekimab sunirine is a CD123-targeting ADC in clinical development for hematological malignancies, including blastic plasmacytoid dendritic cell neoplasm (BPDCN), acute myeloid leukemia (AML), and other CD123+ hematologic malignancies. Pivekimab is currently being evaluated as monotherapy for patients with BPDCN and in combination with Vidaza (azacitidine) and Venclexta (venetoclax) for patients with untreated and relapsed/refractory AML. Pivekimab uses one of ImmunoGen’s novel indolinobenzodiazepine (IGN) payloads, which alkylate DNA and cause single strand breaks without crosslinking. IGNs are designed to have high potency against tumor cells, while demonstrating less toxicity to normal marrow progenitors than other DNA-targeting payloads. The European Medicines Agency (EMA) granted orphan drug designation to pivekimab for the treatment of BPDCN in June 2020. Pivekimab also holds this designation in the US. In October 2020, the FDA granted pivekimab Breakthrough Therapy designation in relapsed/refractory BPDCN.

ABOUT BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM (BPDCN)

BPDCN is a rare form of blood cancer that has features of both leukemia and lymphoma, with characteristic skin lesions, lymph node involvement, and frequent spread to the bone marrow. This aggressive cancer requires intense treatment often followed by stem cell transplant. Despite the approval of a CD123-targeting therapy, the unmet need remains high for patients, both in the frontline and in the relapsed/refractory setting.