Arcotatug tavatecan (IBI343/TAK-921) versus treatment of physician’s choice (TPC) in previously treated, advanced gastric or gastroesophageal junction adenocarcinoma (G/GEJA): First interim analysis of the randomized, open-label, phase 3, G-HOPE-001 study

G-HOPE-001

Paziente / Popolazione Intervento / Esposizione Confronto Esito

In previously treated CLDN18.2-positive advanced gastric or gastro-oesophageal junction adenocarcinoma, arcotatug tavatecan improved progression-free survival compared with treatment of physician's choice.

N

408pazienti

Disegno

Randomised 1:1, open-label, phase 3 trial in patients with unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma with CLDN18.2 IHC ≥2+ in ≥75% of tumour cells who had progressed on 2-4 prior regimens, comparing arcotatug tavatecan with treatment of physician's choice (irinotecan, paclitaxel or trifluridine/tipiracil), stratified by region, primary tumour site and prior gastrectomy (NCT06238843).

Esito

Dual primary endpoints: progression-free survival assessed by independent review per RECIST v1.1, and overall survival.

RisultatoIRRC-assessed median PFS 5.5 months with arcotatug tavatecan vs 2.9 months with treatment of physician's choice (HR 0.47, 95% CI 0.34-0.65; P <0.0001). With 34.8% of events, median OS 9.9 vs 7.4 months (HR 0.63, 95% CI 0.45-0.89). IRRC-assessed ORR 23.6% vs 5.3%. Grade ≥3 TEAEs 45.8% vs 57.9%. Nausea 38.9% vs 40.6%, vomiting 22.2% vs 28.4% and diarrhoea 12.8% vs 34.5%. No interstitial lung disease was observed. TRAEs leading to discontinuation occurred in 1.0% in each arm and no TRAE led to death.

Shitara K, Peng Z, Li C, et al. Presented at ESMO Congress 2026, abstract LBA77, 23 October. Not yet published.

Discussione e critica

At this first interim analysis the trial shows a statistically significant PFS benefit by independent review, with a higher response rate and fewer grade ≥3 adverse events than single-agent chemotherapy. Overall survival is immature, with only 34.8% of events at a futility analysis, no P value and formal testing deferred to the second interim analysis, so a survival benefit is not yet established. The design is open label, although the independent review of PFS limits assessment bias, and all patients were enrolled in China and Japan with high CLDN18.2 expression, which may limit how far the results apply to other populations. The abstract reports only gastrointestinal events among the common adverse events and gives no data on quality of life or haematological toxicity.