CD19-directed CAR-T Therapy MC-1-50 Demonstrates Durable Efficacy in Patients With R/R B-ALL

Chongqing Precision Biotech’s MC-1-50, an investigational CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy currently being evaluated in a phase 1/2 clinical trial (NCT04271410) for the treatment of B-cell leukemia and lymphoma, has demonstrated durable efficacy in patients with relapsed or refractory (r/r) B-cell precursor acute lymphoblastic leukemia (B-ALL). The data were presented in a poster at the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, held June 2-6, in Chicago, Illinois.

MC-1-50 is based on the PrimCAR platform, which is intended to shorten the manufacturing time for the CAR-T product from the 2 weeks seen in conventional manufacture methods to about 2 days. All 19 patients with r/r B-ALL who received MC-1-50 in the trial achieved a complete response (CR) or CR with incomplete hematological recovery (CRi). It was noted that more than half of the patients achieved a sustained CR/CRi without other antitumor therapy. For 11 of the patients, their CRs/CRis remained ongoing at the time of the data cutoff. Seven of the other patients later experienced relapse of their disease; at the time of relapse, 4 of these patients had become CD19-negative and 2 had CD19 mutations. One of the 19 patients died without experiencing relapse. First author Yang Zhi, PhD, the technical director of Chongqing Precision Biotech, and colleagues noted that long-term persistence of CAR T-cells was observed in all 4 of the trial’s dose-levels.

In terms of safety, 18 of the 19 treated patients experienced cases of cytokine release syndrome (CRS). One of these patients experienced a grade 3 case of CRS; all other cases were grade 1 to grade 2. Meanwhile, 2 patients experienced grade 1 cases of immune effector cell-associated neurotoxicity syndrome (ICANS) and 1 patient experienced a grade 2 case of ICANS. There were no grade 3 or higher cases of ICANS reported. Zhi and colleagues noted that CRS and ICANS were graded by American Society for Transplantation and Cellular Therapy criteria.

The ages of the 19 patients ranged from 6 years to 71 years. The group included 9 female patients and 10 male patients. Four of the 19 patients had previously received treatment with hematopoietic stem cell transplantation. Tumor burden at baseline ranged from 0% to 83.0%; it was noted that the one patient with 0% tumor burden only had extramedullary lesions. Prior to infusion of MC-1-50, which was administered as a single dose in the trial, patients received daily preconditioning with 25 to 30 mg/m2 of fludarabine and 200 to 300 mg/m2 of cyclophosphamide for 3 days. Six patients received a dose of 1x10⁵ per kg of MC-1-50 cells; 7 patients were treated at a dose of 2x10⁵ per kg of MC-1-50 cells; 4 patients received a dose of 3x10⁵ per kg of MC-1-50 cells; and 2 patients received a dose of 5x10⁵ per kg of MC-1-50 cells.

“Treatment of r/r B-ALL at a very low dose resulted in excellent safety profiles while exhibiting a high and durable efficacy,” Zhi and colleagues concluded. They pointed out several potential avenues for future research, noting a need to evaluate the safety and efficacy of the product in a study with a larger cohort and an interest in evaluating the PrimCAR technology for the treatment of solid tumors.

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REFERENCE
1. Yang Z, Li S, Li Y, et al. Examining safety and durable disease remission in R/R B-ALL after autologous CD19-directed CAR T cells produced by novel PRIMCAR manufacture platform. Presented at: the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, held June 2-6, in Chicago, Illinois. Abstract #7026 Poster #156