Orphan drug designation granted to a FasTCAR dual-targeting CAR T-cell, GC012F, for the treatment of R/R MM

The U.S. Food and Drug Administration (FDA) has granted orphan drug designation to GC012F, a FasTCAR-enabled B-cell maturation antigen (BCMA)/CD19 dual-targeting chimeric antigen receptor (CAR) T-cell therapy for adult patients with relapsed/refractory multiple myeloma (R/R MM). The decision was based on the results of an ongoing, phase I investigator-initiated trial across multiple centers in China. The trial showed durable responses in patients with R/R MM, including high-risk patients (according to Mayo Stratification for Myeloma and Risk-Adapted Therapy [mSMART] 3.0 criteria) and patients with newly diagnosed MM.¹

About GC012F

GC012F is a BCMA and CD19 dual-targeting CAR T-cell therapy that works by targeting both malignant plasma cells expressing BCMA and CD19-expressing early progenitor cells.

The Multiple Myeloma Hub has previously summarized the progression of CAR T-cell trials in China, specifically on reducing manufacturing times (FasTCAR) and incorporating a second target (dual CAR), which you can find here.

About the trial²

In total, 19 heavily pretreated patients with MM received a single infusion of GC012F at a dose of 1–5×10⁵/kg cells. They had a median of five prior lines of therapy.

• The primary endpoint is the rate of incidence and severity of adverse events after GC012F ≤24 weeks after infusion.
• Secondary endpoints include:
  • percentage of patients with minimal residual disease 12 and 24 weeks after infusion;
  • overall response rate;
  • progression-free survival
  • duration of response
  • overall survival
• Eligibility criteria:
  • confirmed diagnosis of R/R MM
  • adequate liver, kidney, and cardiopulmonary function
  • received at least two prior lines of therapy
  • refractory to both an immunomodulatory drug and a proteasome inhibitor
• Patients with other uncontrolled malignancies, convulsion or stroke within the past six months, clinical evidence of dementia, or who have pulmonary fibrosis were excluded from the study.

Results

• The ORR was 94.7%.
• 100% of patients had reduced paraprotein, with 18 of the 19 patients experiencing a 100% reduction.
• Grade 1/2 cytokine release syndrome (CRS) was seen in 84.2% of patients and Grade 3 in 10.5%.
• No grade 4/5 CRS was observed.
• Two deaths were reported; however, neither were found to be related to study treatment.