#China #Shanghai #CAR-T #CARsgen #GPRC5D

CARsgen's Groundbreaking CT071 CAR-T Therapy for Multiple Myeloma

On October 7, 2025, CARsgen Therapeutics Holdings Limited, listed under Stock Code 2171.HK, published insightful data regarding its innovative CAR T-cell therapy, CT071, which targets GPRC5D. The findings, disseminated in The Lancet Haematology, detail the results from an investigator-initiated trial aimed at addressing relapsed/refractory multiple myeloma (R/R MM). The study highlighted the therapy's safety and preliminary efficacy, demonstrating a noteworthy objective response rate (ORR) of 100% among patients treated.

Study Overview and Patient Demographics

Conducted with a total of 20 patients, the trial (NCT05838131) enrolled individuals battling R/R MM, all of whom had previously undergone a median of five lines of therapy. The patient cohort included diverse challenges: 95% were double-class refractory, and notably, 25% encountered penta-drug refractory conditions. Half of the participants had undergone autologous stem cell transplantation (ASCT), while five relapsed following previous CAR T-cell therapies, underscoring the complexity of their cases.

Among the participants, 20% faced extramedullary disease (EMD), and 70% exhibited high-risk cytogenetics. Most patients fell into the Revised International Staging System (R-ISS) classification levels 2 or 3 at baseline, indicating severe disease progression.

Safety and Efficacy Data

Encouragingly, no dose-limiting toxicities (DLTs) were encountered throughout the study, reflecting a commendable safety profile for CT071. The trial established a recommended phase 2 dose at 0.1×10⁶ CAR T cells/kg. While a significant proportion of patients—60%—experienced cytokine release syndrome (CRS), all cases were classified as mild to moderate (Grade 1 or 2), with no reported instances of Grade 3 or higher CRS. One case of Grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS) was noted, yet there were no treatment-related fatalities, showcasing the potential of CT071 as a safer alternative in the realm of CAR T-cell therapies.

Remarkable Response Rates

The follow-up period averaged 10.71 months, and the results delivered striking effectiveness rates. Out of the 20 evaluable patients, all achieved objective responses—half reached a stringent complete response (sCR), while 20% achieved very good partial response (VGPR) and 30% with partial response (PR). A remarkable instance included a patient with significant EMD, who, after 10 months of treatment, reported a substantial 67.6% tumor reduction.

Furthermore, among the five prior responders to anti-BCMA CAR T therapies, all exhibited therapeutic efficacy with varying degrees of response, emphasizing CT071's potency even in heavily pre-treated patient groups. Impressively, 90% of evaluable patients achieved minimal residual disease (MRD) negativity at a threshold of 10−6, all of whom had reached complete or stringent responses.

The median timeline to achieve MRD negativity stood at a concise 29 days, hinting at the rapid effects of the therapy. However, median durations for response (DoR), progression-free survival (PFS), and overall survival (OS) have yet to be ascertained, reinforcing the need for further investigation as these outcomes evolve.

Next Steps in Clinical Evaluation

CT071 emerges from CARsgen's proprietary CARcelerate® platform, symbolizing their commitment to addressing significant medicinal gaps in the treatment of multiple myeloma and other malignancies. Additional trials are underway aiming to evaluate the therapy's efficacy against newly diagnosed multiple myeloma (NDMM) scenarios.

With a goal to transcend traditional treatment barriers, CARsgen Therapeutics remains steadfast in their mission to innovate CAR T-cell therapies, aspiring for a future where multiple myeloma and similar diseases can be managed effectively, and ultimately cured. As these promising results unfold, the landscape of multiple myeloma treatment looks increasingly hopeful.