CARsgen Presents Initial Human Results of GPRC5D CAR-T CT071 at EHA 2024

CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK), an innovative company focused on CAR T-cell therapies for treating hematologic malignancies and solid tumors, has shared promising initial results from its ongoing first-in-human study of CT071 at the 29th Annual Congress of the European Hematology Association (EHA).

The preliminary findings of Phase I of CT071 (NCT05838131) were featured as a poster presentation during the congress on June 14, under the title "First-in-human study of GPRC5D-targeted CAR T cells (CT071) with an accelerated manufacturing process in patients with relapsed/refractory multiple myeloma (RRMM)."

Multiple myeloma, a common but currently incurable hematologic malignancy, continues to present significant treatment challenges. Despite advancements, many patients relapse and become resistant to existing therapies, indicating a critical need for new treatment options. GPRC5D, a protein predominantly found on the surface of malignant plasma cells but minimally expressed on normal tissues, has emerged as a promising target for multiple myeloma therapy. CT071, a fully human GPRC5D-targeting second-generation CAR T-cell product, has been developed using CARsgen's proprietary CARcelerateTM platform, which notably reduces manufacturing time to approximately 30 hours. This expedites the overall treatment process, enabling quicker delivery and younger T cells. The initial study results suggest that CT071 could potentially be a leading GPRC5D-targeting CAR T-cell therapy.

As of February 28, 2024, 10 patients had been treated with CT071—seven at a dose of 1.0×10^5 cells/kg and three at 3.0×10^5 cells/kg. The cohort included patients with high-risk cytogenetics (80%), extramedullary plasmacytomas (30%), and advanced-stage disease (40% at R-ISS stage III). These patients had undergone extensive prior treatments, with a median of five previous therapy lines. Notably, 90% were double-class refractory, 70% triple-class refractory, 40% penta-drug refractory, 50% had received autologous stem cell transplantation, and 20% had been treated with BCMA/CD19 dual-targeting CAR T cells. The rapid manufacturing turnaround negated the need for bridging therapy.

At a median follow-up of 4.07 months (ranging from 2.8 to 7.4 months), the study reported no Grade 3 or higher cytokine release syndrome (CRS) events, no immune effector cell-associated neurotoxicity syndrome (ICANS), and no adverse events of special interest or dose-limiting toxicity (DLT). Four patients had treatment-related serious adverse events, including pneumonia, decreased appetite, and thrombocytopenia, all of which were resolved.

The overall response rate was 90%, with five patients (50%) achieving stringent complete response (sCR), two patients (20%) exhibiting very good partial response (VGPR), and two others (20%) showing partial response (PR). Among the nine patients who underwent minimal residual disease (MRD) assessment at Week 4, all achieved MRD negativity, including those with sCR/CR. Pharmacokinetic analyses indicated robust cell expansion and persistence, with a median Tmax of 14 days (ranging from 12 to 28 days) and a median Cmax of 32,280.5 copies/μg gDNA (range: 8,372-106,060).

CT071 is being developed for the treatment of relapsed/refractory multiple myeloma (R/R MM) and relapsed/refractory plasma cell leukemia (R/R PCL). The investigator-initiated trial (NCT05838131) in China aims to evaluate its safety and efficacy. Another trial (NCT06407947) is also underway to test its efficacy in newly diagnosed multiple myeloma (NDMM).

CARsgen Therapeutics is dedicated to pioneering CAR T-cell therapies to treat various hematologic and solid tumors. The company operates in both China and the U.S., developing a robust CAR T-cell research and development platform that spans target discovery, clinical trials, and large-scale production. CARsgen's mission is to lead globally in providing innovative and differentiated cell therapies to cancer patients worldwide, aiming to make cancer curable.