First-in-Human Trial of TruUCAR GC027 in Relapsed/Refractory T-Cell ALL Announced

The first-in-human clinical trial for universal TruUCAR GC027 in relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) was announced by Gracell Biotechnologies, the developer of the technology.¹

Data from the trial was presented in the Adoptive Cell Transfer Therapy section during the American Association for Cancer Research (AACR) Virtual Annual Meeting 2020, held April 27-28, 2020. The study of TruUCAR GC027 in relapsed and refractory T-ALL reported early efficacy outcomes from 5 patients treated. 

"We are delighted to report the outcome on the first five patients treated with TruUCAR™ GC027. These promising preliminary results are encouraging and warrant further evaluation of the therapy in this area of high unmet clinical need." Martina Sersch, PhD, chief medical officer of Gracell, said in a press release. 

As of February, the study had enrolled a total of 5 patients with relapsed and refractory T-ALL, with 5 median prior lines of therapy (range 1-9). Baseline bone marrow tumor burden was 38.2% (range 4-80.2). 

Each of the patients received a single infusion of TruUCAR GC027 in 1 of 3 dose levels, including 1 at 0.6*10^7cells/kg, 3 at 1.0*10^7cells/kg, and 1 at 1.5*10^7cells/kg.² Of note, these individuals were not HLA matched, and no one accepted post-infusion hematopoietic stem cell transplantation. 

After 28 days of follow-up, researchers assessed the treatment efficacy in the 5 patients. Overall, all 5 (100%) achieved a complete remission with or without complete blood count recovery. Moreover, 4 (80%) achieved minimum residual disease negative complete remission (MRD-CR). In all 4 patients with MRD-CR, peak expansions of GC027 in peripheral blood were observed between weeks 1 and 2. Even further, in 1 patient with central nervous system disease, GC027 was detected in specimens from his bone marrow and cerebrospinal fluid. 

All 5 patients tolerated the single infusion of TruUCAR GC027 with no neurotoxicity events or acute graft-versus-host disease observed. However, 4 patients experienced grade 3 cytokine release syndrome (CRS) and 1 patient had grade 4 CRS along with elevated levels of IL6, IFNy, and TNFα. CRS symptoms were all manageable though, and resolved after treatment and supportive care. Additionally, 1 patient had prolonged cytopenia due to fungal infection and required anti-fungal therapy. 

Currently, the standard of care therapies for T-ALL are chemotherapy and stem cell transplantation. However, 40-50% of patients will experience relapse within 2 years following front line therapy with limited treatment options available, underscoring the high unmet medical need in patients with relapsed and refractory T-ALL. 

References:

1. Gracell Reports Data of First-in-human Clinical Trial for Universal TruUCAR™ GC027 in Relapsed or Refractory T-cell Acute Lymphoblastic Leukemia at the AACR Virtual Annual Meeting [news release]. Suzhou, China and Shanghai. Published April 28, 2020. finance.yahoo.com/news/gracell-reports-data-first-human-200000315.html?.tsrc=fin-srch. Accessed May 5, 2020. 

2. AACR. CT052 - Clinical safety and efficacy study of TruUCAR™ GC027: The first-in-human, universal CAR-T therapy for adult relapsed/refractory T-cell acute lymphoblastic leukemia (r/r T-ALL). AACR website. Published April 28, 2020. abstractsonline.com/pp8/#!/9045/presentation/10760. Accessed May 5, 2020.