CARsgen's GPRC5D CAR-T Therapy CT071 Achieves 100% Response Rate in Heavily Pretreated Multiple Myeloma Patients
核心洞察
CARsgen (搜索)'s CT071, a GPRC5D (搜索)-targeted CAR-T therapy, demonstrated a 100% objective response rate in 20 heavily pretreated relapsed/refractory multiple myeloma patients in a phase 1 trial published in The Lancet Haematology.
The therapy showed a favorable safety profile with no dose-limiting toxicities, no grade ≥3 cytokine release syndrome, and only one patient experiencing grade 3 neurotoxicity.
Notably, all five patients who had previously failed BCMA (搜索)-targeted CAR-T therapies responded to CT071, with 90% of evaluable patients achieving minimal residual disease negativity.
CARsgen (搜索) Therapeutics has reported promising results from its first-in-human phase 1 trial of CT071, a GPRC5D (搜索)-targeted CAR-T cell therapy for relapsed/refractory multiple myeloma (R/R MM), with findings published in The Lancet Haematology. The investigator-initiated trial (NCT05838131) demonstrated a 100% objective response rate in 20 heavily pretreated patients, marking a significant milestone for this novel therapeutic approach.
Trial Design and Patient Population
The single-center, single-arm phase 1 trial enrolled patients with heavily pretreated disease. Participants had received a median of 5 prior lines of therapy (IQR 3.0-6.5), with 19 patients (95%) being double-class refractory and 13 patients (65%) triple-class refractory. Five patients (25%) were penta-drug refractory, and 10 patients (50%) had previously undergone autologous stem cell transplantation.
Notably, 5 patients (25%) had relapsed after previous CAR-T cell therapies targeting BCMA (搜索) or BCMA/CD19 (搜索), representing a particularly challenging patient population. Additionally, 4 patients (20%) presented with extramedullary disease, 14 patients (70%) had ≥1 high-risk cytogenetics, and 19 patients (95%) had Revised International Staging System (R-ISS) 2 or 3 disease at baseline.
Safety Profile
CT071 demonstrated a favorable safety profile with no dose-limiting toxicities observed across all dose levels tested. The recommended phase 2 dose was established at 0.1×10⁶ CAR-T cells/kg. Cytokine release syndrome occurred in 12 patients (60%), but all cases were graded as 1 or 2, with no grade ≥3 cytokine release syndrome reported.
Only one patient (5%) experienced grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS), and importantly, no treatment-related deaths occurred during the study period.
Efficacy Results
With a median follow-up of 10.71 months (IQR 6.13-12.02), CT071 achieved remarkable efficacy outcomes. The objective response rate reached 100% (95% CI, 83.2-100), with 10 patients (50%) achieving stringent complete response (sCR), 4 patients (20%) achieving very good partial response (VGPR), and 6 patients (30%) achieving partial response (PR).
The therapy demonstrated activity even in patients with extramedullary disease, with one patient presenting a large extramedullary lesion (125 mm×99 mm at baseline) achieving a 67.6% reduction at month 10 with ongoing partial response.
Response in Previously CAR-T Treated Patients
All 5 patients who had previously been treated with anti-BCMA (搜索) CAR-T (n=1) or anti-BCMA/CD19 (搜索) CAR-T (n=4) therapies responded to CT071 treatment. Among these patients, 2 achieved partial response, 1 achieved very good partial response, and 2 achieved stringent complete response, demonstrating the potential of GPRC5D (搜索) targeting in overcoming resistance to BCMA-directed therapies.
Minimal Residual Disease and Durability
Eighteen of 20 evaluable patients (90%) achieved minimal residual disease (MRD) negativity at 10⁻⁶, including all 10 patients with complete response or stringent complete response. The median time to MRD negativity was 29 days (IQR 29-29), indicating rapid disease clearance.
At the data cutoff of December 9, 2024, median duration of response, progression-free survival, and overall survival had not been reached, suggesting durable responses in this heavily pretreated patient population.
GPRC5D as a Therapeutic Target
CT071 utilizes CARsgen (搜索)'s proprietary CARcelerate® platform to target GPRC5D (搜索), a cell surface protein expressed on multiple myeloma cells. This approach represents an alternative targeting strategy for patients who have exhausted BCMA (搜索)-directed therapies, addressing a significant unmet medical need in the multiple myeloma treatment landscape.
Development Pipeline
Beyond the current R/R MM trial, CARsgen (搜索) has initiated an investigator-initiated trial evaluating CT071 in newly diagnosed multiple myeloma patients in China (NCT06407947), potentially expanding the therapeutic application of this GPRC5D (搜索)-targeted approach to earlier lines of treatment.