^
    26d
    Preclinical development and a case report of a nanobody-based CLDN18.2 CAR-T IMC002 with reduced on-target off-tumor toxicity. (PubMed, Mol Cancer Ther)
    The highest non-severely toxic dose was 5×108 CAR-T cells/kg. In the clinical case report, we present a case with unresectable advanced gastric cancer achieved pathological complete response 10 months after IMC002 infusion and no signs of recurrence were indicated in subsequent clinical and radiological follow-ups. IMC002 shows effectiveness and safety in CLDN18.2-positive gastric and pancreatic cancer and its favorable profiles support further clinical development.
    Preclinical • Journal
    |
    CLDN18 (Claudin 18)
    |
    CLDN18.2 positive
    |
    IMC002
    1m
    Modeling and addressing on-target/off-tumor toxicity of claudin 18.2 targeted immunotherapies. (PubMed, Nat Commun)
    However, GI toxicities are reported from clinical use of both Zolbetuximab and CT041...We also demonstrate and characterize on-target/off-tumor gastric toxicity targeting CLDN18.2 in a preclinical mouse model of CT041-scFv derived CAR T cell therapy. By developing CLDN18.2 fully-human VH-only single domain CARs, we demonstrate that on-target/off-tumor toxicity inversely correlates with affinity of the binder, and that a lower affinity CAR may widen the therapeutic window for CLDN18.2 by decreasing on-target/off-tumor toxicity while preserving efficacy.
    Journal • IO biomarker
    |
    CLDN18 (Claudin 18)
    |
    Vyloy (zolbetuximab-clzb) • satricabtagene autoleucel (CT041)
    2ms
    Mechanistic data-informed multiscale quantitative systems pharmacology modeling framework enables the clinical translation and efficacy assessment of CAR-T therapy in solid tumors. (PubMed, J Immunother Cancer)
    Our translational QSP platform offers an innovative pathway to integrate multiscale knowledge and inform clinical decision-making of novel solid tumor-targeting CAR-T therapies.
    Journal
    |
    CLDN18 (Claudin 18)
    |
    LB1908
    2ms
    To Evaluate the Efficacy of CT041 in Sequential Treatment After First-line Treatment of Advanced Gastric/Esophagogastric Junction Adenocarcinoma (clinicaltrials.gov)
    P=N/A, N=20, Recruiting, Beijing GoBroad Hospital | Not yet recruiting --> Recruiting
    Enrollment open
    |
    satricabtagene autoleucel (CT041)
    2ms
    A First-in-human, Dose Escalation and Indication Expansion Study of BNT3212 as Monotherapy or in Combination With BNT327 in Adults With Advanced Solid Tumors (clinicaltrials.gov)
    P1/2, N=375, Recruiting, BioNTech SE | Not yet recruiting --> Recruiting
    Enrollment open • First-in-human
    |
    pumitamig (BNT327)
    3ms
    To Evaluate the Efficacy of CT041 in Sequential Treatment After First-line Treatment of Advanced Gastric/Esophagogastric Junction Adenocarcinoma (clinicaltrials.gov)
    P=N/A, N=20, Not yet recruiting, Beijing GoBroad Hospital
    New trial
    |
    satricabtagene autoleucel (CT041)
    3ms
    A First-in-human, Dose Escalation and Indication Expansion Study of BNT3212 as Monotherapy or in Combination With BNT327 in Adults With Advanced Solid Tumors (clinicaltrials.gov)
    P1/2, N=375, Not yet recruiting, BioNTech SE
    New P1/2 trial
    |
    pumitamig (BNT327)
    4ms
    Noninvasive in vivo tracking of SPIONs-labeled CLDN18.2-targeted CAR-T cells in gastric cancer via magnetic particle imaging. (PubMed, Transl Res)
    On the fifth day post-infusion, the MPI signal of SPIONs-labeled CAR-T cells was significantly higher in the tumor than that of labeled normal T cells. MPI combined with FMI successfully monitored the targeting of CLDN18.2-specific CAR-T cells in gastric cancer, potentially guiding the evaluation of CAR-T therapy combined with aPD-L1 immunotherapy.
    Preclinical • Journal
    |
    CLDN18 (Claudin 18)
    4ms
    Phase 1 Trial of AZD6422 in CLDN18.2+ GI Tumors (clinicaltrials.gov)
    P1, N=8, Completed, Peking University | Recruiting --> Completed | N=96 --> 8 | Trial completion date: Nov 2028 --> Jun 2025 | Trial primary completion date: Jun 2026 --> Jun 2025
    Trial completion • Enrollment change • Trial completion date • Trial primary completion date
    |
    CLDN18 (Claudin 18)
    |
    AZD6422
    5ms
    BAH2573-102: Mesothelin and Claudin 18.2 Dual-Target CAR-T Therapy in Advanced Pancreatic Cancer (clinicaltrials.gov)
    P1/2, N=60, Recruiting, Essen Biotech
    New P1/2 trial
    |
    cyclophosphamide • fludarabine IV
    6ms
    Claudin-18 isoform 2-specific CAR T-cell therapy (satri-cel) versus treatment of physician's choice for previously treated advanced gastric or gastro-oesophageal junction cancer (CT041-ST-01): a randomised, open-label, phase 2 trial. (PubMed, Lancet)
    This is the first randomised controlled trial of CAR T-cell therapy in solid tumours globally. Satri-cel treatment resulted in a significant improvement in progression-free survival, with a manageable safety profile. These results support satri-cel as a new third-line treatment for advanced gastric or gastro-oesophageal junction cancer patients.
    P2 data • Journal • PD(L)-1 Biomarker
    |
    CLDN18 (Claudin 18)
    |
    CLDN18.2 positive
    |
    Opdivo (nivolumab) • paclitaxel • docetaxel • AiTan (rivoceranib) • irinotecan • satricabtagene autoleucel (CT041)
    6ms
    CT041-ST-01: Study to Evaluate the Efficacy, Safety and Pharmacokinetics of CT041 Autologous CAR T-cell Injection (clinicaltrials.gov)
    P1/2, N=192, Active, not recruiting, CARsgen Therapeutics Co., Ltd. | Recruiting --> Active, not recruiting | Trial primary completion date: Jun 2024 --> Oct 2024
    Enrollment closed • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • CLDN18 (Claudin 18)
    |
    HER-2 expression • CLDN18.2 positive
    |
    paclitaxel • AiTan (rivoceranib) • irinotecan • satricabtagene autoleucel (CT041)