according to initial findings from an ongoing study.
The first five patients enrolled in this first-in-human study received conditioning and an infusion of the premanufactured CD7-targeted CAR T-cell therapy, TruUCAR GC027.
All five patients achieved a complete remission (CR) or CR with incomplete count recovery (CRi), although one patient had a morphological relapse at 1 month.
Xinxin Wang, PhD,at the AACR Virtual Meeting I. Dr. Wang is employed by Gracell Biotechnologies in Shanghai, China, which is the company developing TruUCAR GC027.
The CAR T-cell therapy is manufactured using lentivirus and leukopaks from HLA-mismatched healthy donors, according to Dr. Wang. TruUCAR GC027 contains second-generation CAR T cells with genomic disruption of TCR-alpha and CD7 to help prevent graft-versus-host disease and fratricide.
TruUCAR GC027 was previously shown to expand and have antileukemic activity in a murine model, Dr. Wang noted.
Patients and treatment
The five patients in the phase 1 study had a median age of 24 years (range, 19 to 38 years). They had heavily pretreated T-ALL, with a median of 5 prior lines of therapy (range, 1-9). Baseline bone marrow tumor burden ranged from 4% to 80.2% (median, 38.2%).
None of the patients received prior allogeneic hematopoietic stem cell transplant.
All patients received a preconditioning chemotherapy regimen. One patient received TruUCAR GC027 at dose level 1 (6 x 106 cells/kg), three patients received dose level 2 (1 x 107 cells/kg), and one patient received dose level 3 (1.5 x 107 cells/kg) – each as a single infusion.
Expansion, response, and safety
“GC027 expansion, analyzed by flow [cytometry] was observed in most of the patients treated,” Dr. Wang said. “We started to see GC027 in the peripheral blood as early as day 5, with peaks around day 7-14.”
All five patients had a CR or CRi at the first postinfusion evaluation, which occurred at day 14 in four of the five patients. Four patients also achieved minimum residual disease (MRD) negativity by 1 month of follow-up and remained in MRD-negative CR at the February 6, 2020, data cutoff.
One patient achieved MRD-positive CR at day 14 but experienced morphological relapse at 1 month.
In the four patients with MRD-negative CR at 1 month, cellular expansion was observed as early as day 5 and continued for 2 weeks, but the patient who relapsed at day 29 showed no cellular expansion on flow cytometry, Dr. Wang said.
However, by a more sensitive quantitative polymerase chain reaction analysis, cellular expansion was observed in all five patients starting as early as day 1 after infusion, although the patient who relapsed had the shortest duration of expansion.
All patients developed cytokine release syndrome (CRS). Four patients experienced grade 3 CRS, and one experienced grade 4 CRS.
“The CRS was manageable and reversible,” Dr. Wang said, adding that none of the patients experienced neurotoxicity or graft-versus-host disease.
Prolonged cytopenia occurred in four patients, including one grade 1 case, two grade 3 cases, and one grade 4 case. Grade 3 pulmonary infections occurred in three patients, and grade 3 neutropenia occurred in all five patients.