Gracell Continues Progress in R/R B-Cell Acute Lymphoblastic Leukemia


The first patient has been dosed in a phase 2 study of the allogeneic CAR T-cell therapy GC007g.

Gracell Biotechnologies has dosed the first patient in its phase 2 registrational of GC007g for the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) being conducted in China.1

GC007g is an allogeneic, human leukocyte antigen (HLA)-matched, CD19-targeted chimeric antigen receptor (CAR) T-cell therapy being investigated in patients with r/r B-ALL whose disease has relapsed after allogeneic human stem cell transplant. Previous data on GC007g from its phase 1 trial have demonstrated efficacy with a favorable safety profile. The registrational study will further evaluate the recommended phase 2 dose of the therapy in patients with r/r B-ALL.

"B-ALL patients that relapse after allo-HSCT therapy often face poor prognoses, and remain a patient population with a clear unmet medical need. Donor-derived CAR-T therapy could provide a new option to some of these patients who might be ineligible for other treatments including autologous CAR-T therapy," Wendy Li, MD, chief medical officer (CMO),Gracell, said in a statement.1 "We believe GC007g is a potential first-in-class donor-derived allogeneic CAR-T therapy in China. GC007g is also Gracell's first therapeutic candidate to enter a registrational trial, marking an important milestone in our quest to transform cell therapy."

Earlier this year, Gracell announced positive data in B-ALL from a phase 1 invetigator-initiated trial with another allogeneic CAR T-cell therapy candidate, GC502.2 The therapy is developed using Gracell’s TruUCAR technology platform designed to produce efficient, lower-cost, allogeneic cell therapies. 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. It is manufactured using leukopaks from human leukocyte antigen-unmatched healthy donors.

READ MORE: Allogeneic Anti-CD7 CAR-T Demonstrates Promising Results in Hematological Malignancies

As of January 2022, 4 patients have been enrolled 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 heavily pretreated and had received either autologous or allogeneic CD19 or CD19/CD22 targeted CAR-T therapy. 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.

There were cases of treatment-related adverse events (TEAEs) of grade 3 febrile neutropenia, grade 4 thrombocytopenia, and grade 3 anemia, which resolved after standard-of-care (SOC) treatment. Other TEAEs included least grade 3 γ-glutamyl transferase elevations, at least grade 3 aspartate aminotransferase elevations, and at least grade 3 alanine aminotransferase elevations. Grades 2 and 3 cytokine release syndrome also occurred; these cases were manageable with ruxolitinib, SOC and supportive care.

"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,” former CMO Martina Sersch, MD, said in an earlier statement.2 “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.”

1. Gracell Biotechnologies doses first patient in phase 2 portion of registrational phase 1/2 clinical trial evaluating GC007g for treatment of B-cell acute lymphoblastic leukemia. News release. Gracell Biotechnologies. October 17, 2022.
2. 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.
3. 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.
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