G-HOPE-001 Phase III: IBI343 Later-Line Therapy in CLDN18.2-Positive Gastric Cancer Showed PFS 7.1 Months, OS 10.2 Months

Previously, CLDN18.2 has become an important therapeutic target for advanced gastric cancer and gastroesophageal junction adenocarcinoma. The SPOTLIGHT and GLOW studies showed that zolbetuximab combined with chemotherapy improved PFS and OS compared to chemotherapy alone in first-line treatment of CLDN18.2-positive, HER2-negative patients ^[2][4]; CheckMate 649 supports the survival benefit of chemotherapy combined with immune checkpoint inhibitors in HER2-negative gastric cancer ^[1]. However, the prognosis of later-line systemic treatment remains limited ^[1]. CLDN18.2 is also not a rare target: in postoperative pathology cohorts, its positivity rates were 34.4% and 44.4%, respectively, with both studies using the definition of strong membranous staining proportion ≥75% in tumor cells ^[5][6]. The phase I study of the same ADC IBI343 previously showed few grade ≥3 gastrointestinal adverse events, and no interstitial lung disease was reported ^[3].

This ESMO LBA77 presents the results of the China-Japan international multicenter, randomized, open-label phase III G-HOPE-001 study of tanconatamab vedotin (IBI343/TAK-921). The study enrolled patients with locally advanced unresectable or metastatic CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma who had received at least two prior systemic therapies. A total of 464 patients were enrolled, and this second interim analysis included 408 patients randomized 1:1. The control was investigator's choice of irinotecan, paclitaxel, or trifluridine/tipiracil. As of September 3, 2026, the median PFS for tanconatamab vedotin and control were 7.1 months and 3.1 months, respectively, HR=0.45 (95% CI 0.35-0.58), a 55% reduction in the risk of disease progression or death; median OS were 10.2 months and 6.9 months, respectively, HR=0.57 (95% CI 0.45-0.73), a 43% reduction in the risk of death; confirmed ORR was 37.4% and 7.7%.

This result advances IBI343 from phase I safety exploration to a randomized phase III later-line comparison, demonstrating consistent benefit across PFS, OS, and response rate. Regarding safety, the incidence of grade ≥3 TEAEs was 58.3% and 62.6%, and adverse events leading to dose reduction of any grade were 17.8% and 35.1%. The grade ≥3 incidence of nausea, vomiting, and diarrhea were only 0.9%, 2.6%, and 1.3%, respectively, consistent with the low gastrointestinal toxicity observed in phase I ^[3]. The report compares its 7.1-month PFS with first-line immuno-chemotherapy data, but the two are not head-to-head comparisons, and efficacy equivalence cannot be concluded on this basis.

Limitations include that this remains a later-line, open-label study enrolling only Chinese and Japanese patients; open-label design may affect some outcome assessments. OS also comes from interim analysis, requiring longer follow-up. Its results support further investigation of first-line combination and perioperative strategies, but cannot be directly extrapolated to these treatment settings. The CLDN18.2 testing standards and the scope of benefit across different treatment lines also remain to be validated.