Table 1 Anti-mesothelin CAR T cell therapy clinical trials in malignant mesothelioma
From: Anti-Mesothelin CAR T cell therapy for malignant mesothelioma
clinicaltrials.gov Identifier | Phase | Intervention | Additional therapy | Cancer type | Delivery | Sponsor | Study completion | Construct information | Status / Outcome |
|---|---|---|---|---|---|---|---|---|---|
NCT01583686 | I/II | Anti-mesothelinCAR-transduced peripheral blood lymphocytes | fludarabine, cyclophosphamide, IL-2 | MSLN expressing tumors | Systemic | National Cancer Institute (NCI), USA | Dec-18 | SS1 scFv | Terminated due to slow/insufficient accrual. Positive results for safety but low efficacy. Best OR: 1/15 with SD. 14/15 with PD. |
NCT01355965 | I | mRNA anti-MSLN CAR-T cells |  | MPM, PDAC | Systemic | University of Pennsylvania, USA | Oct-15 | SS1 mouse scFv fused to the 4–1-BB and CD3ζ signaling domains | Completed. Positive results (Primary endpoint: safety). Best OR: 2/18 patient showed transient response (Ref. 32, 33). |
NCT02159716 | I | Anti-MSLN CAR-T cells (CART-meso) |  | MPM, PDAC, ovarian | Systemic | University of Pennsylvania, USA | Nov-15 | SS1 mouse scFV fused to the 4-1BB and CD3ζ signaling domains | Completed. Positive results (Primary endpoint: safety). Low persistence and low tumor infiltration were observed. Best OR: 6/15 patients with SD (Ref. 34). |
NCT03054298 | I | Anti-MSLN CAR-T cells (huCART-meso) | cyclophosphamide | MSLN expressing tumors | Systemic and intrapleural | University of Pennsylvania, USA | Mar-21 | SS1 humanized scFV | Recruiting. |
NCT03608618 | I | mRNA anti-MSLN CAR PBMC (MCY-M11) | cyclophosphamide | Peritoneal Mesothelioma,Fallopian Tube and ovary Adenocarcinoma,Primary Peritoneal Carcinoma | Intraperitoneal | MaxCyte, Inc., USA | May-22 | NA | Recruiting. Preliminary results (ASCO 2020): positive results on safety. 4/11 patients with SD (Ref. 35). |
NCT02414269 | I/II | Anti-MSLN CAR-T cells with suicide switch (iCasp9M28z) | cyclophosphamide or pembrolizumab | MPM | Intrapleural | Memorial Sloan Kettering Cancer Center, USA | Apr-21 | anti-MSLN scFv linked to the CD28 and CD3ζ signaling domains plus suicide gene inducible caspase 9 | Recruiting. Preliminary results (AACR 2019, ASCO 2019): positive results on safety, 2/19 patients with CR, 5/19 with PR, 4/19 with SD (Ref. 36, 37). |
NCT04577326 | I | anti-MSLN CAR T cells with intrinsic anti-PD1 inhibition (M28z1XXPD1DNR) | cyclophosphamide | MPM | Intrapleural | Memorial Sloan Kettering Cancer Center, USA | Sep-22 | anti-MSLN scFv linked to the CD28 and CD3ζ signaling domains plus PD-1 DNR and 1XX ITAM modification | Recruiting. |
NCT03907852 | I/II | Anti-MSLN TRuC (TC-210) | cyclophosphamide, pembrolizumab, fludarabine | MSLN expressing tumors | Systemic | TCR2 Therapeutics, USA | Jan-23 | single-domain anti-MSLN antibody fused to the CD3-ε subunit | Recruiting. Preliminary results in 5 patients show positive results on safety and 2/5 patients with unconfirmed PR (Ref. 38). |
NCT04489862 | I | Anti-MSLN CAR-T cells expressing PD-1 nanobodies | Â | MPM, NSCLC | Systemic | Wuhan Union Hospital, China | Dec-22 | NA | Recruiting. |
NCT03638206 | I/II | Anti-MSLN CAR-T cells | cyclophosphamide, fludarabine | MPM | Systemic | Shenzhen BinDeBio Ltd., China | Mar-23 | NA | Recruiting. |