Table 4 Selected investigational HER2–targeted agents for mGC
From: Gastric cancer treatment: recent progress and future perspectives
Approach | Agents | Trial | Phase | Lines | Treatment | Outcomes | References |
|---|---|---|---|---|---|---|---|
Monoclonal antibody | Margetuximab | MAHOGANY | II/III | 1st line | Margetuximab ± PD-1 inhibitor ± chemotherapy ± dual checkpoint inhibitor | Cohort A (margetuximab plus retifanlimab): ORR 53% (95% CI 36.1–68.5); DCR 73% (95% CI 56.1–85.4); mPFS 6.4 months (95% CI 6.0-NE); mOS not reached | [123] |
Bispecific antibodies | Zanidatamab (ZW25) | Ku, G., et al | II | 1st line | ZW25 + chemotherapy (CAPOX or FP) | ORR 75%; mDOR 16.4 months; mPFS 12.0 months | [124] |
HERIZON-GEA-01 | III | 1st line | ZW25 + chemotherapy with or without tislelizumab vs. trastuzumab + chemotherapy | Ongoing | [125] | ||
KN026 | Xu et al | II | 2nd or later lines | KN026 | Cohort 1(HER2 IHC3 + or IHC 2 + ISH +): ORR 56% (95% CI 35%-76%); mDoR 9.7 months (95% CI 4.2- NE); mPFS 8.3 months (95% CI 4.2–11.4); mOS 16.3 months (95% CI 11.0- NE) Cohort 2 (HER2 IHC 1 + /2 + ISH- or IHC 0/1 + ISH +): ORR 14% (95% CI 2%-43%); mDoR 6.2 months (95% CI 3.2-NE); mPFS 1.4 months (95% CI 1.4–4.1); mOS 9.6 months (95% CI 3.5–14.9) | [127] | |
PRS-343 | - | II | 2nd or later lines | PRS-343 + ramucirumab + paclitaxel; PRS-343 + tucatinib | Ongoing | NCT05190445 | |
ADC | Trastuzumab deruxtecan (T-Dxd) | DESTINY-Gastric01 | II | 3rd or later lines | T-Dxd vs. chemotherapy (Irinotecan or Paclitaxel) | ORR 51% vs. 14%, P < 0.001; mOS 12.5 vs. 8.4 months (HR 0.59; 95% CI, 0.39 to 0.88; P = 0.01); mPFS 5.6 vs. 3.5 months (HR 0.47; 95% CI, 0.31 to 0.71) | [132] |
DESTINY-Gastric02 | II | 2nd line | T-Dxd | ORR 41.8%, mPFS 5.6 months (95% CI 4.2–8.3 months); mOS 12.1 months (95% CI 9.4–15.4 months) | [134] | ||
RC48 | RC48-C008 | II | 3rd or later lines | RC48 | ORR 24.8% (95% CI 17.5%-33.3%); mPFS 4.1 months (95% CI 3.7–4.9 months); mOS 7.9 months (95% CI 6.7–9.9 months) | [137] | |
ARX788 | Zhang, Y., et al | I | 2nd or later lines | ARX788 | ORR 37.9% (95% CI 20.7%-57.7%); DCR 55.2% (95% CI 35.7%-73.6%); mPFS 4.1Â months (95% CI 1.4-6.4Â months); mOS 10.7Â months (95% CI 4.8-not reached) | [138] | |
TKI | Tucatinib | MOUNTAINEER-02 | II/III | 2nd-line | Phase II: Tucatinib + trastuzumab + ramucirumab + paclitaxel Phase III: Arm A: Tucatinib + trastuzumab + ramucirumab + paclitaxel Arm B: Placebo + ramucirumab + paclitaxel Arm C: Tucatinib + ramucirumab + paclitaxel | Ongoing | NCT04499924 |