XPJ(中国)有限公司官网

This clinical trial utilized a single-arm, dose-escalation trial withtraditional three plus three(3+3) design in Fudan University Shanghai Cancer Centerin China to evaluate the low, medium, and high dose groups of CGC729 (DL1: 5 x 10⁶/m²; DL2: 1.5 x 10⁷/m²; DL3: 4.5 x 10⁷/m²). As of April 2024, five patients who had received at least two prior treatments were enrolled and received a single infusion of CGC729. All patients underwent a three-day lymphodepletion regimen.

Safety Evaluation: As of April 11, 2024, all five patients (three in DL1 and two in DL2) experienced no dose-limiting toxicities (DLTs). The most common adverse events were reductions in neutrophils, platelets, and white blood cells related to lymphodepletion, with no greater than grade 2 cytopenia observed. One patient in DL1 (0102) developed grade 2 cytokine release syndrome (CRS), which resolved within 24 hours; the same patient also developed grade 2 immune effector cell-associated neurotoxicity syndrome (ICANS), successfully treated with corticosteroids.

Efficacy Evaluation: In the eligible patients, the overall response rate (ORR) reached 50% (2/4), and the disease control rate (DCR) reached 75% (3/4). Among the three CD70 positive patients, the overall response rate (ORR) was 66.7% (2/3), with two patients achieving partial response (PR), demonstrating promising efficacy and high anti-tumor activity with ongoing response duration up to 6 months. Furthermore, pharmacokinetic measurement showed robust expansion of CGC729 in all subjects, regardless of the CD70 expression level in the tumor, with sustained presistence observed up to 20 weeks.

Conclusion: The interim analysis of this first-in-human trial shows that anti-CD70 CAR-NKT (CGC729) has a good safety profile and significant anti-tumor activity, providing a new treatment possibility for advanced metastatic clear cell renal cell carcinoma.

The challenge of treating solid tumors is compounded by tumor heterogeneity and a suppressive tumor microenvironment (TME), which are major barriers to successful CAR-T cell therapy. Addressing this, Natural Killer T (NKT) cells, a subset of multifactorial innate-like T cells, offer new possibilities in solid tumor therapy due to their multifactorial anti-tumor capabilities and TME modulation properties.

Cure Genetics' innovative AIMS CAR-NKT platform is based on these NKT cell features, aimed at enhancing solid tumor infiltration, modulating the TME, and prolonging sustained expansion. This platform has demonstrated good safety and promising efficacy in our lead product, CGC729, and is concurrently being expanded to other autologous/allogeneic products.

RCC has a high prevalence and poor prognosis globally, with a 5-year survival rate of only 12%. Post TKI and ICI therapies, treatment options are very limited.

CGC729 is an autologous anti-CD70 CAR-NKT with a differentiated mechanism of action from T cells and NK cells. First, CGC729 combines adaptive and innate immunity with multiple tumor-killing mechanisms targeting CD70, CD1d, and stress ligands frequently expressed in RCC. Additionally, CGC729 has the capability to modulate the TME through skewing macrophage differentiation and resisting TGF-β inhibition.

Cure Genetics, established in Suzhou in 2016, is a clinical-stage company dedicated to developing cell and gene therapies for solid tumors and common genetic diseases. With our innovative technology platforms, including the Universal CAR-NKT platform AIMS CAR-NKT and the unique AAV platform VELP™, Cure Genetics is at the forefront of original innovation, achieving a differentiated pipeline layout. By leveraging global collaborations and out-licensing, we actively drive research and development, and the commercialization of innovative drugs. We aim to provide effective treatment options for patients worldwide with unmet medical needs and to establish ourselves as a benchmark in the global field of cell and gene therapy.