FDA Pipeline: Designations for Treatments of Rare Blood Cancer, B-Cell Malignancies, and Gastric Cancers

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Recently, the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation to an antibody-drug conjugate for the treatment of patients with relapsed or refractory blastic plasmacytoid dendritic cell neoplasm (BPDCN); gave Fast Track designation to a novel chimeric antigen receptor (CAR) T-cell therapy in patients with B-cell malignancies; and granted Orphan Drug designation to a first-in-class drug candidate for the treatment of gastric and gastroesophageal junction adenocarcinoma.

Breakthrough Therapy Designation for IMGN632 in Relapsed or Refractory Blastic Plasmacytoid Dendritic Cell Neoplasm

The FDA granted Breakthrough Therapy designation to IMGN632 for the treatment of patients with relapsed or refractory 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 recent approval of a CD123-targeting therapy, the unmet need remains high for patients, particularly in the relapsed/refractory setting.

IMGN632 is a CD123-targeting antibody-drug conjugate in clinical development for hematological malignancies, including BPDCN, acute myeloid leukemia, and acute lymphocytic leukemia. IMGN632 uses one a novel indolino-benzodiazepine (IGN) payloads, which alkylate DNA without crosslinking. IGNs have been designed to have high potency against acute myeloid leukemia blasts, while demonstrating less toxicity to normal marrow progenitors than other DNA-targeting payloads.

Breakthrough Therapy designation was granted for IMGN632 based on the findings from the BPDCN cohort of the first-in-human study of IMGN632, for which initial data were presented in an oral session at the American Society of Hematology (ASH) Annual Meeting & Exposition in 2019. Updated data from the IMGN632 monotherapy BPDCN dose expansion cohort will be presented at the ASH meeting this December.

Fast Track Designation for ‘Switchable’ CAR T-Cell Therapy, CLBR001 + SWI019, in B-Cell Malignancies

The FDA granted Fast Track designation to a novel “switchable” CAR T-cell therapy. The therapy is currently being evaluated as a treatment for B-cell malignancies, a class of blood cancers that includes non-Hodgkin lymphoma and chronic lymphocytic leukemia.

A phase I trial has begun patients to assess the safety and tolerability of the cell therapy. The study is being conducted at multiple sites in the United States.

The investigational CAR T-cell therapy leverages patients’ own immune cells to treat cancer, putting the cells under control of a novel molecular “switch” that seeks to mitigate potentially life-threatening side effects that have hampered the use of cell therapies to date.

Some patients who receive T-cell therapies experience an adverse effect called cytokine-release syndrome, which occurs when the immune system reacts too strongly. The switchable CAR T-cell platform incorporates an antibody known as SWI019 that acts as a switch, activating the engineered cells (CLBR001) and directing them to engage the cancer target. This mechanism may allow doctors to have more control over the therapy, which could provide a significant safety advantage.

In preclinical studies, the approach proved highly effective at eliminating tumors while controlling the level of cytokines produced in response to treatment.  Further, by switching the CLBR001 cells “on” and “off” the approach allows the engineered cells to “rest,” which in preclinical models afforded greater efficacy.

Orphan Drug Designation for CT041 CLDN18.2 CAR-T Cells in Gastric and Gastroesophageal Junction Cancers

The FDA granted orphan drug designation to one of a first-in-class drug candidate, CT041, for the treatment of gastric and gastroesophageal junction adenocarcinoma. CT041 is a humanized anti-claudin18.2 autologous chimeric antigen receptor (CAR) T-cell product, and is targeted to treat patients with claudin18.2-positive tumors.

CT041 is the first claudin18.2-targeted CAR T-cell therapy that has received Investigational New Drug (IND) clearance by the FDA and the first to receive IND clearance by the National Medical Products Administration in China. The initiation of an open-label, multicenter, phase Ib clinical trial to evaluate the safety and efficacy of autologous CT041 cell therapy in patients with advanced gastric, gastroesophageal, or pancreatic adenocarcinoma is currently underway.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.