Data of its first-in-human clinical trial for Universal TruUCAR™ GC027 in relapsed or refractory (R/R) T-cell acute lymphoblastic leukemia patients was presented as part of the Adoptive Cell Transfer Therapy section of the virtual annual meeting of the American Association for Cancer Research (AACR) held April 27 and 28, 2020.
TruUCAR™, being developed by Shanghai-based Gracell Biotechnologies, is a proprietary and patented platform technology, with selected genes being edited to avoid Graft Versus Host Disease (GvHD) and immune rejection without using strong immunosuppressive drugs. In addition to the T-ALL antigen, the platform technology can also be implemented for other targets of hematological malignancies.
GC027 is an investigational, off-the-shelf Chimeric Antigen Receptor T-cell (CAR T-cell) therapy, redirected to CD7 for the treatment of T-cell malignancies. GC027 was manufactured from T-cells of human leukocyte antigen (HLA) unmatched healthy donors using TruUCAR™ technology, which is expected to improve efficacy and reduce production time, available for off-the-shelf use in a timely manner.
T-cell acute lymphoblastic leukemia
T-cell acute lymphoblastic leukemia, also known as T-ALL, is an aggressive form of acute lymphoblastic leukemia, with a diffuse invasion of bone marrow and peripheral blood. On average 20-25% of adult ALL patients, and 12-15% of pediatric ALL patients will be diagnosed with this form of leukemia. The disease is hard-to-treat with a high unmet clinical need. 
The current standard of care therapies for T-ALL include chemotherapy and stem cell transplantation. However, 40-50% of patients will experience relapse within two years of diagnosis and following front line therapy, including multi-agent chemotherapy regimens. Relapsed disease remains very difficult to salvage and these patients are generally left with very limited treatment options. As a result, survival rates are generally lower than 25%. 
Hematopoietic cell transplantation is considered the only curative treatment, but successful remission reinduction is a prerequisite, which has remained a significant challenge. Historical reinduction remission rates in T-ALL are estimated to be 30% to 40%. 
The study of TruUCAR™ GC027 in relapsed and refractory T-ALL reports early efficacy outcomes of five patients treated. The clinical investigator’s initial trial (IIT) evaluated the safety and efficacy of TruUCAR™ GC027, the first-in-human, universal CAR T-cell therapy for R/R T-ALL. As of February 2020, the study enrolled a total of five patients with R/R T-ALL, with median prior lines of therapy 5 (range 1-9).
The baseline bone marrow tumor burden was 38.2% (range 4-80.2). All patients received a single infusion of TruUCAR™ GC027 in one of three dose levels: 0.6*10^7cells/kg, 1.0*10^7cells/kg or 1.5*10^7 cells/kg. Notably, these patients were not HLA matched, and no one accepted post-infusion hematopoietic stem cell transplantation (HSCT).
Treatment efficacy was assessed in five patients with 28 days of follow-up, of which:
- Five (100%) achieved a complete remission with or without complete blood count recovery (CR/CRi);
- Four (80%) achieved minimum residual disease negative complete remission (MRD-CR).
All five participating patients tolerated the single infusion of TruUCAR™ GC027. The researchers involved in the trial did not observe neurotoxicity events or acute graft-versus-host disease (aGvHD). Cytokine release syndrome (CRS) presented in all patients at any grade.
“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.” concluded Martina A. Sersch, M.D., Ph.D., the Chief Medical Officer of Gracell.
 Raetz EA, Teachey DT. T-cell acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program. 2016;2016(1):580–588. doi:10.1182/asheducation-2016.1.580
 Jabbour E, Pui CH, Kantarjian H. Progress and Innovations in the Management of Adult Acute Lymphoblastic Leukemia. JAMA Oncol. 2018;4(10):1413–1420. doi:10.1001/jamaoncol.2018.1915
 Kantarjian HM, Thomas D, Ravandi F, et al. Defining the course and prognosis of adults with acute lymphocytic leukemia in first salvage after induction failure or short first remission duration. Cancer. 2010;116(24):5568–5574. doi:10.1002/cncr.25354
 Reismüller B, Attarbaschi A, Peters C, et al; Long-term outcome of initially homogenously treated and relapsed childhood acute lymphoblastic leukaemia in Austria–a population-based report of the Austrian Berlin-Frankfurt-Münster (BFM) Study Group Br J Haematol. 2009; 144 (4): 559-570.