Clinical Summary: 

• Kohei Shitara, MD, discusses results from the phase 3 G-HOPE-001 trial comparing arcotatug tavatecan, a novel CLDN18.2-directed antibody-drug conjugate, with physician's choice of chemotherapy in patients with previously treated unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.
• At the prespecified first interim analysis, arcotatug tavatecan significantly improved progression-free survival compared with chemotherapy (5.5 months vs 2.9 months; HR, 0.47), with higher objective response rates and fewer grade ≥3 treatment-emergent adverse events.
• These findings support further evaluation of arcotatug tavatecan as a later-line treatment option for CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma, demonstrating clinically meaningful disease control with manageable toxicity.

Kohei Shitara, MD, National Cancer Center Hospital East, Kashiwa, Japan, discusses results from the phase 3 G-HOPE-001 trial evaluating arcotatug tavatecan, a novel CLDN18.2-targeted antibody-drug conjugate (ADC), versus physician's choice of chemotherapy in patients with previously treated unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma. 

Dr Shitara reviews the significant progression-free survival benefit observed with arcotatug tavatecan, along with improved response rates and a manageable safety profile compared with chemotherapy. He also discusses the potential role of CLDN18.2-targeted ADC therapy in expanding biomarker-directed treatment options for patients with advanced gastric or gastroesophageal junction adenocarcinoma. 

Transcript: 

Hello, I'm Kohei Shitara. I'm a GI oncologist working in Japan. At this ESMO meeting, we present primary results from the phase 3 G-HOPE-001 study.

G-HOPE-001 is a randomized phase 3 study conducted in China and Japan, comparing arcotatug tavatecan (AT), as a novel CLDN18.2-targeted ADC, compared with third-line or later-line chemotherapy for CLDN18.2-positive G/GEJ cancer.

AT is a novel CLDN18.2 ADC with an exatecan-derived payload and silenced Fc function designed to reduce Fc-mediated on-target, off-tumor toxicities. In the control arm, irinotecan is the most commonly used drug.

As a result, the primary end point (PFS)  at the first interim analysis showed statistically significant improvement with AT. Median PFS was 5.5 months versus 2.9 months, with a hazard ratio of 0.47 and a significant P value. The 6-month PFS rate was 49% with AT and 24% with chemotherapy.

This study also met the additional primary end point (OS) at the second interim analysis. Median OS was 10.2 months with AT and 6.9 months with chemotherapy. The hazard ratio was 0.57, with a significant P value. And the 1-year OS rate was 43% versus 25%.

For both PFS and OS, the subgroup analysis showed consistent benefit of AT in the majority of subgroups. Also, the response rate in patients with measurable lesions by central assessment at IA2 showed a higher response rate with AT (37% versus 8%),  there was nearly a 30% difference. Median duration of response was approximately 10 months with AT.

The safety is very important in this population. Median duration of treatment was 3 months longer with AT (5 months versus 2 months). Nevertheless, grade ≥3 treatment-related adverse events were less frequent with AT compared with chemotherapy, occurring in 47% versus 56%. 

Overall safety profiles were generally manageable. GI toxicities were also comparable or less frequent with AT compared with chemotherapy.

In summary, this G-HOPE-001 study demonstrated PFS and OS improvement with AT compared with third-line and later-line chemotherapy in CLDN18.2-positive G/GEJ cancer, with a manageable safety profile, and it supports this regimen as a very effective later-line treatment option for G/GEJ cancer.

Source: 

Shitara K, Peng Z, Li C, et al. 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. Presented at ESMO Congress. October 23-27, 2026; Madrid, Spain. LBA77.