Allogeneic CAR T-Cell Therapy Shows Promise in R/R B-Cell Acute Lymphoblastic Leukemia

Article

The phase 1, investigator-initiated trial continues to recruit participants with B-ALL.

The allogeneic chimeric antigen receptor (CAR) T-cell therapy TruUCAR GC502 has demonstrated promising efficacy in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL).1

These data, from an ongoing phase 1 investigator-initiated trial, were presented at the 2022 American Association for Cancer Research (AACR) Annual Meeting, April 8-13, 2022, in New Orleans, Louisiana, by Xinxin Wang, PhD, vice president, research and development, Gracell.

"As an allogeneic, off-the-shelf CAR-T therapy, GC502 has the potential to provide patients who may not be eligible for autologous CAR-T therapy with hope to achieve a deep response,” Martina Sersch, MD, chief medical officer, Gracell, said in a statement.2

GC502 is a CD19/CD7 dual directed CAR and contains a T cell enhancer and genetically disrupted TRAC and CD7 loci to avoid graft versus host disease (GvHD) and fratricide. The therapy is manufactured using leukopaks from human leukocyte antigen-unmatched healthy donors.

Four patients have been enrolled in the study, which continues to recruit participants, and treated with doses of 1.0x107 cells/kg or 1.5x107 cells/kg of 1 of 2 different formulations (A and B) of GC502. Patients were lymphodepleted by fludarabine and cyclophosphamide prior to infusion. Patients ranged from 15 to 34 years of age, were heavily pretreated, and had received either autologous or allogeneic CD19 or CD19/CD22 targeted CAR-T therapy. They had a median of 48.1% baseline marrow blast levels (range, 19.5-92). One patient had extramedullary involvement.

As of January 28, 2022, all patients had received a single dose of GC502. One patient received the lower dose level and 3 received the higher. Three patients were evaluable at 28 days after treatment and 2 of these had achieved a complete response (CR). One patient achieved a partial response (PR) and subsequently received hematopoietic stem cell transplantation on day 39.

Treatment-related adverse events (TEAEs) did occur, with 2 cases of grade 3 febrile neutropenia, 1 case of grade 4 thrombocytopenia, and 3 cases of grade 3 anemia in the 3 evaluable patients. These TEAEs resolved after standard of care treatment. Other TEAEs included 3 cases of at least grade 3 γ-glutamyl transferase elevations, 2 cases of at least grade 3 aspartate aminotransferase elevations, and 3 cases of at least grade 3 alanine aminotransferase elevations.

Grade 2 cytokine release syndrome (CRS) occurred in 2 patients treated with formulation B of GC502 while grade 3 CRS occurred in 2 patients treated with formulation A (duration, 7 and 10 days). These cases were manageable and resolved after treatment with ruxolitinib, SOC and supportive care. Investigators observed no cases of immune effector cell-associated neurotoxicity syndrome or acute GvHD were observed.

Investigators assessed cellular expansion and found that the patient treated at the lower dose level did not show adequate GC502 cellular expansion. In the second dose level, peak expansion in peripheral blood was observed between week 1 to 2. Median peak CAR copies were 149,945 copies/ug DNA (range 10,849-195,400).

“The early results show the potential of GC502 and warrant further evaluation in the ongoing clinical investigator-initiated-trial. Being the second product candidate from our allogeneic TruUCAR platform, GC502 further validates TruUCAR's platform approach and potential wide applicability,” Sersch added.2

REFERENCES
1. Li S, Wang X, Yuan Z, et al. Early results of a safety and efficacy study of allogeneic TruUCAR™ GC502 in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). Presented at: 2022 American Association for Cancer Research Annual Meeting. April 8-13, 2022; New Orleans, Louisiana. Abstract CT196/21.
2. Gracell Biotechnologies to Present Data at AACR Annual Meeting 2022 Showcasing Early First-in-Human Results for GC502 in r/r B-ALL. News release. Gracell Biotechnologies. April 8, 2022. https://ir.gracellbio.com/news-releases/news-release-details/gracell-biotechnologies-present-data-aacr-annual-meeting-2022
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