Phase 3 Trial of Ciltacabtagene Autoleucel Meets Primary Endpoint in Relapsed, Refractory Multiple Myeloma

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The trial is the first randomized phase 3 study evaluating the efficacy and safety of ciltacabtagene autoleucel patients with relapsed and lenalidomide-refractory multiple myeloma.

The phase 3 CARTITUDE-4 trial evaluating ciltacabtagene autoleucel (Carvykti, Johnson & Johnson) in patients with relapsed and lenalidomide-refractory multiple myeloma met its primary endpoint of a significant improvement in progression-free survival (PFS) at the first pre-specified interim analysis.

As a result of meeting the primary endpoint, the Independent Data Monitoring Committee recommended the unblinding of the study. The trial is evaluating ciltacabtagene autoleucel versus pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab, pomalidomide, and dexamethasone (DPd).

“The CARTITUDE-4 study represents the first phase 3 program in our comprehensive clinical development strategy for Carvykti, and further demonstrates our commitment to advance the treatment of patients with relapsed/refractory multiple myeloma,” said Jordan Schecter, MD, vice president of clinical development for the cellular therapy program at Janssen Research and Development, in a press release. “We look forward to the presentation of the data from the CARTITUDE-4 study at a future medical meeting.”

Multiple myeloma is a blood cancer that affects plasma cells found in the blood marrow. In multiple myeloma, these plasma cells change, spread rapidly, and replace normal cells in the bone marrow with tumors. In 2023, more than 35,000 individuals will be diagnosed with multiple myeloma and more than 12,000 patients will die from the disease in the United States.

The trial is the first randomized phase 3 study evaluating the efficacy and safety of ciltacabtagene autoleucel. The primary endpoint is PFS and secondary endpoints are safety, overall survival, minimal residual disease negative rate, and overall response rate. Patients enrolled in the trial will continue to be followed for primary, secondary, and exploratory endpoints for the duration of the study.

Ciltacabtagene autoleucel received FDA approval in February 2022 for the treatment of adults with relapsed or refractory multiple myeloma after 4 or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. It is a BCMA-directed, genetically modified autologous T-cell immunotherapy, which involves reprogramming a patient’s own T-cells with a transgene encoding chimeric antigen receptor (CAR) that directs the CAR-positive T-cells to eliminate cells that express BCMA.

BCMA is primarily expressed on the surface of malignant multiple myeloma B-lineage cells, as well as late-stage B cells and plasma cells. The ciltacabtagene autoleucel CAR protein features 2 BCMA-targeting single domains designed to confer high avidity against human BCMA. Once it binds to BCMA-expressing cells, the CAR promotes T-cell activation, expansion, and elimination of target cells.

REFERENCE

Janssen Announces Unblinding of Phase 3 CARTITUDE-4 Study of Carvykti (cilta-cel) as Primary Endpoint Met in Treatment of Patients with Relapsed and Refractory Multiple Myeloma. News release. Johnson & Johnson; January 27, 2023. Accessed February 1, 2023. https://www.jnj.com/janssen-announces-unblinding-of-phase-3-cartitude-4-study-of-carvykti-cilta-cel-as-primary-endpoint-met-in-treatment-of-patients-with-relapsed-and-refractory-multiple-myeloma

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