FDA places a clinical hold on the MELANI-01 study in patients with R/R MM

On July 6, 2020, the U.S. Food and Drug Administration (FDA) placed a clinical hold on the MELANI-01 study (NCT04142619) investigating the use of UCARTCS1A, a preparation of allogeneic, engineered T cells expressing anti-CS1 chimeric antigen receptor (CAR), in patients with relapsed/refractory multiple myeloma (R/R MM). This was due to the submission of a safety report regarding one patient who experienced a fatal cardiac arrest that was deemed to be a treatment-emergent adverse event.¹

The patient had been treated unsuccessfully prior to enrollment with numerous lines of therapy, including autologous CAR T cells, and was being treated at dose level two of UCARTCS1A. However, before the clinical hold, preliminary data assessments had suggested that the recommended phase II dose was dose level one. Therefore, it was decided to expand enrollment at this dose level, and updates to the clinical protocol were being initiated to reflect this as well as to monitor and mitigate additional potential risks with UCARTCS1A.

Clinical evaluation of the case remains ongoing, and additional details as to the immediate and underlying causes of this event are being collected.

UCARTCS1A²

• Allogeneic, off-the-shelf, gene-edited T-cell product candidate
• Designed for the treatment of CS1/SLAMF7-expressing hematologic malignancies
• The FDA approved the Investigational New Drug application for R/R MM in January 2019

Study design³

• Phase I, open-label, dose-escalation study of UCARTCS1A in adult patients with R/R MM
• Aim: To evaluate the safety, expansion, persistence, and clinical activity of UCARTCS1A over 24 months
• An estimated 18 patients who met the following criteria were included:
  • Confirmed diagnosis of active MM (as defined by International Myeloma Working Group criteria) who had relapsed after prior lines of therapy
  • Eastern Cooperative Oncology Group Performance Status of 0 or 1
  • No previous treatment with investigational gene or CAR therapy targeting CS1

For more information on ongoing clinical trials of CAR therapies in multiple myeloma, read our article here.

On November 17, 2020, the FDA lifted the clinical hold after adjustments to the trial protocol to enhance patient safety had been made.⁴