^
    3ms
    Claudin18.2 as a Promising Therapeutic Target in Gastric Cancer. (PubMed, Cells)
    This narrative review presents the characterization and role of claudin 18.2 (CLDN18.2) as a promising biomarker in GC and a target for clinical therapies, more specifically CLDN18.2-targeted drugs and therapies including mABs (e.g., Zolbetuximab, Osemitamab, ZL-1211), bsAB, and CAR-T cell-based immunotherapies. We also summarize numerous ongoing worldwide clinical trials that are evaluating CLDN18.2 as a target for GC treatment. What seems to be crucial is that preclinical and clinical data indicate their high efficacy and safety.
    Review • Journal • IO biomarker
    |
    CLDN18 (Claudin 18)
    |
    Vyloy (zolbetuximab-clzb) • ZL-1211 • osemitamab (TST001)
    8ms
    TransStar101: A Trial to Evaluate Safety and Tolerability of TST001 in Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1/2, N=150, Active, not recruiting, Suzhou Transcenta Therapeutics Co., Ltd. | Trial completion date: Dec 2024 --> Sep 2025 | Trial primary completion date: Nov 2024 --> May 2025
    Trial completion date • Trial primary completion date
    |
    Opdivo (nivolumab) • gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • oxaliplatin • leucovorin calcium • osemitamab (TST001)
    1year
    TranStar102: A Trial to Evaluate Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of TST001 in Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1/2, N=320, Recruiting, Suzhou Transcenta Therapeutics Co., Ltd. | Trial completion date: Nov 2024 --> May 2025 | Trial primary completion date: Aug 2024 --> Feb 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • CLDN18 (Claudin 18)
    |
    HER-2 negative
    |
    Opdivo (nivolumab) • cisplatin • gemcitabine • paclitaxel • capecitabine • oxaliplatin • osemitamab (TST001)
    1year
    TransStar101: A Trial to Evaluate Safety and Tolerability of TST001 in Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1/2, N=150, Active, not recruiting, Suzhou Transcenta Therapeutics Co., Ltd. | Recruiting --> Active, not recruiting | Trial primary completion date: Jun 2024 --> Nov 2024
    Enrollment closed • Trial primary completion date • Combination therapy • Metastases
    |
    Opdivo (nivolumab) • gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • oxaliplatin • leucovorin calcium • osemitamab (TST001)
    1year
    Claudin 1, 4, 6 and 18 isoform 2 as targets for the treatment of cancer (Review). (PubMed, Int J Mol Med)
    The human/humanized anti‑CLDN18.2 mAb osemitamab, and ADCs AZD0901, IBI343 and LM‑302, with single‑agent ORRs of 28‑60%, have been tested in phase III clinical trials. In addition, bsAbs, CAR T cells and their derivatives targeting CLDN4, 6 or 18.2 are in phase I and/or II clinical trials. AZD0901, IBI343, zolbetuximab and the anti‑CLDN1 mAb ALE.C04 have been granted fast track designation or priority review designation by the US Food and Drug Administration.
    Review • Journal
    |
    CLDN18 (Claudin 18) • CLDN6 (Claudin 6) • CLDN1 (Claudin 1)
    |
    Vyloy (zolbetuximab-clzb) • sonesitatug vedotin (AZD0901) • ALE.C04 • osemitamab (TST001) • arcotatug tavatecan (IBI-343)
    over1year
    Osemitamab (TST001) plus nivolumab and CAPOX as the first-line therapy for the patients with advanced G/GEJ cancer (TranStar102) (ESMO 2024)
    P1/2 | "Updated data indicate that the combination of TST001 plus nivolumab and CAPOX as the 1L treatment for patients with G/GEJ cancer is safe and well tolerated with very encouraging anti-tumor activities, especially for patients with high/medium CLDN18.2 expression when cross comparing to historical data."
    Clinical
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • CLDN18 (Claudin 18)
    |
    PD-L1 expression • HER-2 negative • CLDN18.2 expression • CLDN18.2 positive • HER-2 negative + CLDN18.2 positive
    |
    PD-L1 IHC 28-8 pharmDx • Claudin18.2 IHC 14G11 pharmDx
    |
    Opdivo (nivolumab) • osemitamab (TST001)
    over1year
    First-line osemitamab (TST001) plus nivolumab and capox for advanced g/GEJ cancer (TranStar102): Results of cohort G from a phase I/IIa study. (ASCO 2024)
    P1/2 | "Preliminary data indicate that the combination of TST001 6mg/kg Q3W plus nivolumab and CAPOX for the 1st line treatment of patients with G/GEJ cancer is safe and well tolerated with encouraging preliminary anti-tumor activities. Updated clinical data, including PFS and DoR will be reported at the time of the conference. Clinical trial information: NCT04495296."
    Clinical • P1/2 data
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • CLDN18 (Claudin 18)
    |
    PD-L1 IHC 28-8 pharmDx • Claudin18.2 IHC 14G11 pharmDx
    |
    Opdivo (nivolumab) • osemitamab (TST001)
    over1year
    TranStar102: A Trial to Evaluate Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of TST001 in Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1/2, N=320, Recruiting, Suzhou Transcenta Therapeutics Co., Ltd. | Trial completion date: Apr 2024 --> Nov 2024 | Trial primary completion date: Dec 2023 --> Aug 2024
    Trial completion date • Trial primary completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • CLDN18 (Claudin 18)
    |
    HER-2 negative
    |
    Opdivo (nivolumab) • cisplatin • gemcitabine • paclitaxel • capecitabine • oxaliplatin • osemitamab (TST001)
    over1year
    Transcenta Announces Collaboration with Agilent to Develop a Claudin18.2 Companion Diagnostic to Support Osemitamab (TST001) Global Phase III Trial (PRNewswire)
    "Transcenta Holding Limited...and Agilent Technologies, announce a collaboration to develop a Claudin18.2 (CLDN18.2) companion diagnostic to support TranStar301 global Phase III pivotal trial of Osemitamab (TST001) in combination with Nivolumab and chemotherapy as first-line treatment in patients with CLDN18.2 expressing locally advanced or metastatic gastric or gastroesophageal (G/GEJ) adenocarcinoma."
    Licensing / partnership
    |
    Claudin18.2 IHC 14G11 pharmDx
    |
    osemitamab (TST001)
    almost2years
    [Lu]Lu-labeled anti-claudin-18.2 antibody demonstrated radioimmunotherapy potential in gastric cancer mouse xenograft models. (PubMed, Eur J Nucl Med Mol Imaging)
    In preclinical studies, [Lu]Lu-TST001 demonstrated significant antitumor efficacy with acceptable toxicity. It exhibits strong potential for clinical translation, providing a new promising treatment option for CLDN18.2-overexpressing tumors, including GC.
    Preclinical • Journal
    |
    CLDN18 (Claudin 18)
    |
    CLDN18.2 expression • CLDN18.2 positive • CLDN18.2 overexpression • CLDN1 overexpression
    |
    osemitamab (TST001)
    2years
    Combination of TST001, Nivolumab and Chemotherapy as First-line Therapy in Advanced or Metastatic GC/GEJ Adenocarcinoma (clinicaltrials.gov)
    P3, N=950, Not yet recruiting, Suzhou Transcenta Therapeutics Co., Ltd.
    New P3 trial • Metastases
    |
    PD-L1 (Programmed death ligand 1)
    |
    PD-L1 expression
    |
    Opdivo (nivolumab) • 5-fluorouracil • capecitabine • oxaliplatin • leucovorin calcium • osemitamab (TST001)
    over2years
    TST001 in Patients With CLDN18.2 Positive Previously Treated Advanced Biliary Tract Cancer (clinicaltrials.gov)
    P2, N=8, Completed, Shanghai Zhongshan Hospital | Recruiting --> Completed | N=40 --> 8 | Trial completion date: Jul 2024 --> May 2023
    Trial completion • Enrollment change • Trial completion date • Metastases
    |
    CLDN18 (Claudin 18)
    |
    CLDN18.2 expression
    |
    osemitamab (TST001)