Table 4.
Summary of phase I/II trials of CLDN18.2-targeting therapy.
| Design/result/adverse event | NCT04632108 | TranStar102 trial (NCT04495296) |
NCT05009966 | NCT04805307 |
NCT03874897 (Interim results) |
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|---|---|---|---|---|---|---|---|---|
| Phase | I/II | I/IIa | I | I | I | |||
| Treatment | ASKB589 | CAPOX+ASKB589 | CAPOX + Osemitamab (TST001) | SYSA1801 | CMG901 | CT041 | ||
| Agent type | mAb | mAb | ADC | ADC | CAR-T cells | |||
| Cancer type (cohort) | GC (A) | GC (B) | GC | GC | PC | GC/PC | GC | Others |
| N (all) | N = 40 | N = 45 | N = 64 | N = 26 | N = 7 | N = 27 | N = 28 | N = 9 |
| N (efficacy analyzed) | N = 21 | N = 24 |
N = 42 (ORR) N = 64 (PFS) |
N = 17 | N = 4 |
N = 8 (CLDN18.2-positive GC) |
N = 28 | N = 9 |
| ORR | 9.5% | 75% | 66.7% | 47.1% | 0% | 75.0% | 57.1% | 22.2% |
| DCR | 47.6% | 100% | 97.6% | 64.7% | 25% | 100% | 75.0% | 66.7% |
| mPFS | Not released | Not released | 9.5 m | Not released | Not reached | 4.2 m | 2.6 m | |
| OS | Not released | Not released | Not released | Not released | Not reached | 6 m OS: 81.2% | 6 m OS: 77.8% | |
| TRAEs ⩾ Gr1 | 80% | 81% | 100.0% | 75.8% | 96.3% | 100.0% | ||
| Nausea ⩾ Gr1 | 53% | 76% | 70.3% | 42.4% | 40.7% | 48.6% | ||
| Vomiting ⩾ Gr1 | 43% | 66% | 53.1% | 36.4% | 70.4% | 35.1% | ||
| Other common TRAEs ⩾ Gr1 |
Hypoalbuminemia (40%) Loss of appetite (30%) |
Hypoalbuminemia (52%) Granulocytopenia (38%) | Anemia (82.8%) Hypoalbuminemia (65.4%) |
Dry eye syndrome (21.2%) Anemia (21.2%) | Decreased appetite (59.3%) Hypoalbuminemia (44.4%) | CRS Gr1, 2: 94.6% (CRS Gr⩾3 CRS: 0%) |
||
| TRAEs ⩾ Gr3 | 10% | 38% | 65.6% | 24.2% | 11.1% | 100% (almost hematology) | ||
| DLT | None | None | None | Two DLTs at the 3 mg/kg dose (Gr3 nausea and vomiting) |
One DLT at 2.2 mg/kg | None | ||
| MTD | Not reached | Not reached | Not reached | Reached | Not reached | Not reached | ||
| TRD | None | None | None | None | 1 (3.7%) | None | ||
| Reference | Zhang et al. 74 | Shen et al., 75 Guo et al. 76 | Wang et al. 77 | Xu et al. 78 | Qi et al. 79 | |||
ADC, Antibody-Drug Conjugate; CAPOX, Capecitabine + Oxaliplatin; CAR-T, Chimeric Antigen Receptor-T cell; CRS, Cytokine Release Syndrome; DCR, Disease Control Rate; DLT, Dose-Limiting Toxicity; GC, Gastric Cancer; Gr, Grade; m, months; mAb, Monoclonal Antibody; mPFS, median Progression-Free Survival; MTD, Maximum Tolerated Dose; ORR, Objective Response Rate; OS, Overall Survival; PC, Pancreatic Cancer; TRAEs, Treatment Related Adverse Events; TRD, Treatment Related Death.