Takeda: Arcotatug Tavatecan (TAK‑921) improves OS and PFS in Phase 3 gastric cancer trial

Study design

G‑HOPE‑001 is an international, randomized, open‑label Phase 3 study in China and Japan comparing arcotatug tavatecan 6 mg/kg every three weeks versus treatment of physician’s choice (irinotecan, paclitaxel or trifluridine/tipiracil) in 464 patients with unresectable locally advanced or metastatic CLDN18.2‑positive gastric or gastroesophageal junction adenocarcinoma who progressed after 2–4 prior systemic regimens. CLDN18.2 positivity was defined as IHC ≥2+ in ≥75% of tumor cells. Dual primary endpoints were PFS (RECIST v1.1, IRRC) and OS.

Efficacy results

At the second prespecified interim analysis (data cutoff 3 Sept 2026) the study met both primary endpoints. Median OS was 10.2 months with arcotatug versus 6.9 months with physician’s choice (HR=0.57; 95% CI 0.45–0.73; P<0.0001). IRRC‑assessed median PFS was 7.1 months versus 3.1 months (HR=0.45; 95% CI 0.35–0.58). Confirmed objective response rate per IRRC was 37.4% with arcotatug versus 7.7% with physician’s choice. The first interim analysis (data cutoff 13 Feb 2026) had already shown a significant PFS benefit (median 5.5 vs 2.9 months; HR=0.47; 95% CI 0.34–0.65; P<0.0001).

Safety

The overall safety profile was reported as generally manageable. Grade ≥3 treatment‑related adverse events occurred in 47.4% of arcotatug‑treated patients versus 55.9% with physician’s choice. Most common Grade ≥3 events with arcotatug included anemia (20.4%), decreased neutrophil count (17.4%) and decreased white blood cell count (11.7%). Incidence of Grade ≥3 nausea, vomiting and diarrhea was low (0.9%, 2.6% and 1.3%, respectively). Dose interruptions occurred in 47.4% (arcotatug) versus 51.4% (physician’s choice); treatment‑related discontinuations were uncommon (1.7% with arcotatug). One treatment‑related fatal event (sudden death of unknown cause) was reported in the arcotatug arm.

Regulatory and next steps

Takeda plans a regulatory filing in Japan based on these data; Innovent’s NDA in China has been accepted with Priority Review. Takeda also plans to initiate global Phase 3 trials of arcotatug tavatecan in gastric and pancreatic cancer and continue global development. Arcotatug tavatecan remains investigational and not approved by regulatory authorities.