On May 10, 2024 Cure Genetics reported the safety and efficacy data of their CAR-NKT product, CGC729, for patients with relapsed and refractory metastatic renal cell carcinoma (R/R mRCC) in an oral presentation at the 27th Annual Meeting of the American Society for Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper) in Baltimore (Press release, CureGenetics, MAY 10, 2024, View Source [SID1234643645]). This marked the first-in-human trial using CAR-NKT therapy for R/R mRCC, demonstrating a good safety profile and encouraging anti-tumor activity.
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This phase I dose-escalation clinical trial was conducted at Fudan University Shanghai Cancer Center using a single-arm, 3+3 design to evaluate the safety and efficacy of CGC729 at three dose levels (DL1: 5 x 106/m2; DL2: 1.5 x 107/m2; DL3: 4.5 x 107/m2) in the treatment of R/R mRCC patients who had at least two lines of prior therapy. As of April 2024, five patients were enrolled and received a single infusion of CGC729. All patients underwent lymphodepletion prior to CGC729 infusion.
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 lymphodepletion-related neutropenia, thrombocytopenia, and leukopenia. 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), which improved rapidly after symptomatic treatment.
Efficacy Evaluation: Among four eligible patients, the overall response rate (ORR) reached 50% (2/4). Among CD70 positive patients (n=3),ORR was 66.7% (2/3), with two patients achieving partial response (PR). CGC729 demonstrated promising efficacy with deep anti-tumor activity. The longest duration of response (DOR) is continuing at nine-month after treatment. Furthermore, pharmacokinetic measurements showed robust expansion of CGC729 in all subjects, regardless of the CD70 expression level in the tumor, with prolonged persistence in the blood 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 robust anti-tumor activity. It may provide a promising treatment option for R/R mRCC in the future.
About the ASGCT (Free ASGCT Whitepaper) Presentation
Title：Interim Safety and Efficacy Evaluation of Anti-CD70 CAR-NKT (CGC729) Phase I Study for Patients with Relapsed and Refractory Metastatic Renal Cell Carcinoma (R/R mRCC)
No：Late-breaking Abstract No. 10
Format：Oral presentation
Room：Ballroom 4
Time：2024/5/10 8:30 am – 8:45 am
Presenter：Dr. Yuanyuan Qu, Fudan Univeristy Shanghai Cancer Center
About AIMS CAR-NKT
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.
About CGC729
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.