First-in-human phase I study of UCL70802, a LACO-Stim armored Anti-CD70 CART cell therapy, in patients with metastatic clear cell renal cell carcinoma (mccRCC)
Presenter: Yangbing Zhao, MD;PhD Session: Phase I Clinical Trials in Progress Time: 4/20/2026 9:00:00 AM → 4/20/2026 12:00:00 PM
Authors
Xinxin Gan 1 , Wei Li 2 , Wei Zhang 1 , Jiean Ding 1 , Jiatao Hu 1 , Changshun Wu 2 , Lingling Lu 2 , Cong Han 2 , Xiaojun Liu 2 , Yangbing Zhao 2 , Linhui Wang 1 1 Department of Urology, Changhai Hospital, Naval Medical University, Shanghai, China, 2 UTC Therapeutics INC., Shanghai, China
Abstract
Background: UCL70802 is a novel autologous CART product engineered to co-express an anti-CD70 CAR and a Lymphocyte-APC-Co-stimulator (LACO-Stim) molecule, designed to target CD70-positive tumors through dual mechanisms: direct tumor lysis via CAR engagement and systemic immune activation via LACO-Stim. LACO-Stim provides co-stimulation through CD40 and CD28, enhancing T cell and APC function, remodeling the tumor microenvironment, and promoting anti-tumor immunity. Methods: Eligible patients with CD70 positive mccRCC who failed standard therapies were enrolled. Primary endpoints included safety, dose-limiting toxicities, and maximum tolerated dose. Secondary endpoints covered pharmacokinetics and antitumor response per RECIST v1.1. Results: As of December 30, 2025, 6 patients were treated. Safety analysis showed manageable Grade 1-2 cytokine release syndrome (CRS) in 4 patients and Grade 3 CRS in 2 patients (recover to Grade 2 in 1 day). Treatment-related adverse events (TRAEs) included lymphopenia (100%), erythema (100%), and edema (83.3%). All Grade 3 or higher TRAEs were hematological toxicities associated with the lymphodepletion. NO DLTs were observed. Anti-tumor activity was observed across all dose levels except one patient with the dose of 0.6×10⁶/kg (DL1). At the dose level of 2×10⁶/kg (DL3), 2 out of 3 patients achieved a partial response (PR). One patient achieved a conformed PR (-68.9%). The other patient experienced a tumor shrinkage at M1(-17.3%) and achieved PR at M2 (-32.3%). There is a correlation between dose and CAR-T exposure. In DL3, the median peak CAR copy number (Cmax) reached 37750 copies/μg, which is much higher than in DL2. Notably, one patient at DL2 demonstrated mild exposure with C max of 1,368 copies/μg DNA yet achieved sustained tumor shrinkage. Although CAR copies were undetectable at M1, tumor shrinkage persisted for over six months, with tumor reduction increasing from -17.4% at M1 to -26.5% at M6. This indicates that after the initial antitumor response induced by anti-CD70 CAR-T cells, sustained activity was maintained by the innate immune system activated via the LACO-Stim molecule. Conclusions: UCL70802 demonstrated a manageable safety profile and promising preliminary antitumor activity in mccRCC patients. Its dual mechanism -combining direct CAR-mediated targeting with systemic immune activation via LACO-Stim-may help overcome resistance seen with conventional CAR-T therapies. Dose escalation continues to further assess efficacy and safety.
Disclosure
X. Gan, None.. W. Li, None.. W. Zhang, None.. J. Ding, None.. J. Hu, None.. C. Wu, None.. L. Lu, None.. C. Han, None.. X. Liu, None.. Y. Zhao, None.. L. Wang, None.
Cited in
Control: 10615 · Presentation Id: 12175 · Meeting 21436