FDA Grants Breakthrough Therapy Designation to CD123-Directed Antibody-Drug Conjugate

The FDA granted a Breakthrough Therapy designation to IMGN632 as treatment of patients with relapsed or refractory blastic plasmacytoid dendritic cell neoplasms.

The FDA has granted a Breakthrough Therapy designation to IMGN632 as treatment of patients with relapsed or refractory blastic plasmacytoid dendritic cell neoplasms (BPDCN), ImmunoGen, Inc., announced in a press release.

“We are pleased FDA has granted Breakthrough Therapy designation for IMGN632, our novel CD123-targeted ADC, as it underscores the urgent need for effective and well-tolerated treatments for patients with this rare and aggressive cancer,” said Mark Enyedy, president and chief executive officer, ImmunoGen, in a statement. “We look forward to continuing to work with FDA to further define the development path for IMGN632 in BPDCN, in addition to pursuing our ongoing evaluation of IMGN632 in AML and other hematological malignancies.”

IMGN632, a CD123-targeting antibody-drug conjugate (ADC), is in clinical development for the treatment of hematologic malignancies like BPDCN, acute myeloid leukemia (AML), and acute lymphocytic leukemia in clinical trials. The agent is under evaluation as monotherapy in patients with BPDCN and minimal residual disease (MRD)-positive AML after induction treatment, as well as in combination with venetoclax (Venclexta) plus azacitidine (Vidaza) in patients with relapsed/refractory AML.

BPDCN, a rare blood cancer, is known to have features associated with both leukemias and lymphomas, with characteristic skin lesions, lymph node involvement, and frequent spread to the bone marrow. This is an aggressive cancer that requires intense treatment regimens that are often followed by stem cell transplantation. This represents a patient population of unmet need, particularly those in the relapsed/refractory setting.

The phase 1/2 open-label, multicenter clinical trial of IMGN632 plus venetoclax and azacitidine is investigating the safety and efficacy, as well as assess the antileukemic activity of the combination in patients with relapsed assessed in frontline CD123-positive AML. The antileukemia activity of the monotherapy will also be assessed in patients with MRD-positive AML.

The primary end points of the study include safety and tolerability, preliminary antileukemia activity, and MRD levels. The study is currently recruiting and is exploring several different doses of the ADC. IMGN632 will be assessed in combination and monotherapy across multiple regimen arms. Arm A will assess azacitidine, arm B venetoclax, arm C azacitidine plus venetoclax, and arm D will evaluate IMGN632 monotherapy in patients with MRD+ AML.

For arms A through C, a phase 1b dose-escalation cohort in arms A through C will determine the recommended phase 2 dose, and a phase 2 dose-expansion phase will further evaluate each regimen in arms A through D to characterize the safety profile and assess the antileukemia activity. Arm D will open with a dose-expansion cohort, using the ADC monotherapy dose and schedule based on the findings from the initial phase 2 IMGN632-0801 study, and there will be no dose-escalation portion.

To be included in the trial, patients must be at least 18 years of age, have a confirmed AML diagnosis, and be deemed appropriate for this experimental therapy per the treating physician. Patients must have CD123-positive AML to be included in the study, and they were allowed to have received prior CD123-targeted therapies, as long as they have not received IMGN632. Patients had to have an ECOG performance status ≤ 1 and resolution of any prior treatment-related toxicities to either grade 1 or baseline.

Patients cannot have received any anticancer therapy within 14 days before administration of the study drug, prior IMGN632 therapy, a myeloproliferative neoplasm-related secondary AML, or active central nervous system AML. They are also ineligible if they have a history of sinusoidal obstruction syndrome/venous occlusive disease of the liver, myocardial infarction within 6 months of enrollment, or clinically relevant active infection, including known active hepatitis B or C, HIV infection, cytomegalovirus, or other infectious diseases that would make the patient inappropriate for enrollment to this study.


ImmunoGen announces FDA breakthrough therapy designation for IMGN632 in relapsed or refractory blastic plasmacytoid dendtritic cell neoplasm. News Release. ImmunoGen, Inc. October 5, 2020. Accessed October 5, 2020. https://bit.ly/3ljtSFt