Takeda Announces Arcotatug Tavatecan (TAK-921) Demonstrated Statistically Significant and Clinically Meaningful Improvements in Overall Survival and Progression-Free Survival in Phase 3 Advanced Gastric Cancer Study

Takeda(TSE:4502/NYSE:TAK)announced positive results from the Phase 3 G-HOPE-001 study (NCT06238843) of arcotatug tavatecan (TAK-921; Innovent R&D code: IBI343) in patients with Claudin (CLDN)18.2-positive, previously treated, advanced gastric or gastroesophageal junction adenocarcinoma (G/GEJA). Results from two prespecified interim analyses, which were shared in a late-breaking oral presentation at the 2026 European Society for Medical Oncology (ESMO) Congress, showed the study met its dual primary endpoints of overall survival (OS) and progression-free survival (PFS).

Gastric cancer is a leading cause of cancer-related death worldwide, and outcomes are particularly poor once the disease is advanced.¹ Because treatment options are limited for people whose cancer continues to progress after multiple therapies, there is a significant need for new targeted therapies.² CLDN18.2, a protein found at abnormally high levels on the surface of certain cancer cells, has emerged as a key biomarker and therapeutic target for some gastrointestinal cancers, including gastric cancer.³ Arcotatug tavatecan is a novel, potential best-in-class CLDN18.2-targeted antibody-drug conjugate (ADC) with an exatecan payload and an Fc-silenced backbone designed to reduce risk of Fc-mediated side effects. Under a license and collaboration agreement with Innovent, Takeda holds the rights to develop, manufacture and commercialize arcotatug tavatecan worldwide outside of greater China.

“People with advanced gastric cancer whose disease has progressed after multiple prior therapies face limited treatment options and poor survival outcomes,” said Kohei Shitara, M.D., Ph.D., G-HOPE-001 study author and director of the Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan. “In the Phase 3 G-HOPE-001 study, arcotatug tavatecan helped patients live longer and significantly extended the time without disease progression compared with commonly used later-line treatments. Together with its manageable safety profile, these findings highlight the potential for arcotatug tavatecan to offer meaningful clinical benefit and become an important new treatment option for patients with advanced CLDN18.2-positive gastric cancer.”

Results Signal Meaningful Benefit for Patients with Limited Options
The G-HOPE-001 study met both prespecified primary endpoints of OS and PFS, with arcotatug tavatecan demonstrating statistically significant improvements compared with treatment of physician’s choice (TPC) (irinotecan, paclitaxel or trifluridine/tipiracil).

The recently completed second prespecified interim analysis (IA2) evaluated OS. Results from IA2, with a data cutoff of September 3, 2026, showed:

• Statistically significant and clinically meaningful improvement in OS. Median OS was 10.2 months with arcotatug tavatecan versus 6.9 months with TPC (HR=0.57 [95% CI: 0.45-0.73], P<0.0001).
• Clinically meaningful improvement in PFS. Independent radiological review committee (IRRC)-assessed median PFS was 7.1 months with arcotatug tavatecan versus 3.1 months with TPC (HR=0.45 [95% CI: 0.35-0.58]).
• Higher objective response rate (ORR). The confirmed ORR per IRRC assessment was 37.4% with arcotatug tavatecan versus 7.7% with TPC.
• The overall safety profile of arcotatug tavatecan was generally manageable.
  • Among patients receiving arcotatug tavatecan monotherapy, the overall safety profile was manageable, with a Grade ≥3 treatment-related adverse event rate of 47.4% versus 55.9% with TPC.
  • The most common Grade ≥3 treatment-emergent adverse events (TEAEs) with arcotatug tavatecan versus TPC included anemia (20.4% vs. 13.1%), decreased neutrophil count (17.4% vs. 32.0%) and decreased white blood cell count (11.7% vs. 22.5%).
  • There was a low incidence of severe gastrointestinal events with Grade ≥3 nausea, vomiting and diarrhea occurring in 0.9%, 2.6% and 1.3% of patients receiving arcotatug tavatecan, respectively, compared with 1.8%, 3.2% and 4.1% with TPC. This characteristic of the safety profile differentiates arcotatug tavatecan and may ease this aspect of treatment burden for patients in the future.
  • TEAEs leading to dose interruption were reported in 47.4% of patients treated with arcotatug tavatecan versus 51.4% with TPC. Treatment-related drug discontinuations were uncommon and comparable between treatment arms, occurring in 1.7% of patients receiving arcotatug tavatecan. One treatment-related fatal adverse event, reported as sudden death of unknown cause, occurred in the arcotatug tavatecan arm.

The first prespecified interim analysis (IA1) included the final analysis of PFS and an assessment of OS futility, with a data cutoff of February 13, 2026. Results from IA1 showed:

• Statistically significant and clinically meaningful improvement in PFS. IRRC-assessed median PFS was 5.5 months with arcotatug tavatecan versus 2.9 months with TPC (HR=0.47, 95% CI: 0.34-0.65; P<0.0001).

G-HOPE-001 is an international, multicenter, randomized, open-label study being conducted in China and Japan to evaluate arcotatug tavatecan monotherapy versus TPC in patients with previously treated, unresectable locally advanced or metastatic CLDN18.2-positive G/GEJA. Additional post-hoc analyses from the ongoing study will be shared at a future medical congress.

Takeda to Continue Advancing Global Development of Arcotatug Tavatecan
Data from G-HOPE-001 will support a planned regulatory filing for this indication in Japan. In China, Innovent’s New Drug Application for arcotatug tavatecan has been accepted with Priority Review by the National Medical Products Administration.

“These potentially practice-changing data from G-HOPE-001 not only support the path toward our first regulatory filing and continued global development of arcotatug tavatecan but also mark meaningful progress in translating promising science into new treatment options for patients with a range of challenging CLDN18.2-positive cancers, including gastric and pancreatic cancer,” said Phuong Khanh (P.K.) Morrow, M.D., Head of the Oncology Therapeutic Area Unit at Takeda.

Building on ongoing proof-of-concept studies in these settings, Takeda plans to initiate global Phase 3 trials of arcotatug tavatecan in gastric and pancreatic cancer.

Arcotatug tavatecan is an investigational compound that has not been approved for use by the U.S. Food and Drug Administration (FDA) or any other regulatory authorities.

About Arcotatug Tavatecan
Arcotatug tavatecan is a next-generation antibody-drug conjugate (ADC) that targets Claudin (CLDN)18.2-expressing tumor cells. CLDN18.2 is a protein typically found in the lining of a healthy stomach but is abnormally expressed on the surface of cancer cells in certain tumors, making it a target for new cancer therapies.³ Arcotatug tavatecan combines an anti-CLDN18.2 antibody with the cytotoxic agent exatecan, a topoisomerase I inhibitor (TOPO1i). It also incorporates an Fc-silenced structural design intended to minimize off-tumor, on-target toxicity.

Arcotatug tavatecan has received Fast Track Designation from the U.S. Food and Drug Administration (FDA) for the treatment of patients with CLDN18.2-positive, locally advanced or metastatic pancreatic cancer who have received two prior systemic therapies.

About the G-HOPE-001 Study
The Phase 3 G-HOPE-001 study (NCT06238843) is an ongoing, international, multicenter, randomized, open-label study evaluating arcotatug tavatecan monotherapy versus treatment of physician’s choice (TPC) (irinotecan, paclitaxel or trifluridine/tipiracil) in patients with previously treated, unresectable locally advanced or metastatic Claudin (CLDN)18.2-positive gastric or gastroesophageal junction adenocarcinoma (G/GEJA). Eligible patients had CLDN18.2-positive tumors, defined as IHC ≥2+ in ≥75% of tumor cells as measured by the VENTANA CLDN18 (43-14A) Assay, and had progressed on two to four prior systemic regimens. Patients were randomized 1:1 to receive arcotatug tavatecan 6 mg/kg once every three weeks or TPC, stratified by region, primary tumor site and prior gastrectomy. The study’s dual primary endpoints are progression-free survival (PFS) per RECIST v1.1 and overall survival (OS). Secondary endpoints include objective response rate (ORR), disease control rate, duration of response, time to response and safety. The study enrolled 464 participants across Japan and China.

About Gastric and Gastroesophageal Junction Adenocarcinoma (G/GEJA)
Gastric cancer is the fifth most common cancer and fifth leading cause of cancer-related deaths worldwide with Japan and China among the highest-incidence regions globally.^1,4 Five-year net survival rates vary globally but are approximately 20% to 40%, with markedly poorer rates in patients with advanced disease.⁵ Treatment options become increasingly limited as the disease progresses, and median overall survival remains less than 10 months for patients receiving later lines of therapy.⁶ Claudin 18.2, a tight junction protein typically found in healthy gastric tissue but abnormally expressed on the surface of tumor cells in a significant proportion of G/GEJA cancers, has emerged as an important biomarker-driven target for the development of novel precision therapies in this disease.³

About Takeda
Takeda is focused on creating better health for people and a brighter future for the world. We aim to discover and deliver life-transforming treatments in our core therapeutic and business areas, including gastrointestinal and inflammation, rare diseases, plasma-derived therapies, oncology, neuroscience and vaccines. Together with our partners, we aim to improve the patient experience and advance a new frontier of treatment options through our dynamic and diverse pipeline. As a leading values-based, R&D-driven biopharmaceutical company headquartered in Japan, we are guided by our commitment to patients, our people and the planet. Our employees in approximately 80 countries and regions are driven by our purpose and are grounded in the values that have defined us for more than two centuries. For more information, visit www.takeda.com.

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