TOKYO, October 14, 2025 – Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, “Astellas”) today announced the Phase 2 GLEAM trial investigating zolbetuximab in combination with gemcitabine plus nab-paclitaxel versus gemcitabine plus nab-paclitaxel in metastatic pancreatic adenocarcinoma patients did not meet its primary endpoint of overall survival (OS) at final analysis. The safety profile of the zolbetuximab combination was generally consistent with the known profiles of each individual therapy.
The Company will complete a full evaluation of the data from GLEAM and work with investigators on the future dissemination of the results, including secondary end points and subgroup analyses.
Moitreyee Chatterjee-Kishore, Ph.D., M.B.A., Head of Oncology Development, Astellas:
“While we acknowledge that the GLEAM trial did not meet its primary endpoint, we extend our heartfelt gratitude to all trial participants for their invaluable contributions. Our unwavering commitment to pancreatic cancer research remains firm. We recognize the immense challenges posed by this notoriously difficult-to-treat disease and are dedicated to advancing a robust pipeline of innovative investigational treatments aimed at providing hope and improved outcomes for patients facing this devastating and aggressive disease.”
The impact of this result on Astellas’ financial results for the fiscal year ending March 31, 2026, is expected to be minor.
About the GLEAM Trial of Zolbetuximab in Pancreatic Cancer
The Phase 2 GLEAM trial of zolbetuximab in metastatic pancreatic adenocarcinoma involved 393 adult patients from 136 study centers across the US, Europe, Asia, and Australia. The randomized, open-label trial evaluated the safety and efficacy of zolbetuximab in combination with gemcitabine plus nab-paclitaxel as a first-line treatment in patients with metastatic pancreatic adenocarcinoma whose tumors are CLDN18.2 positive (defined as ≥75% of tumor cells demonstrating moderate to strong membranous CLDN18 staining assessed using an immunohistochemistry assay).1
For more information, please visit clinicaltrials.gov under Identifier NCT03816163.
About Pancreatic Cancer
Pancreatic cancer is the 12th most common cancer worldwide and the sixth most common cause of cancer-related death.2 Global incidence and mortality rates continue to rise for both men and women, with over 510,000 cases diagnosed in 2022 and 467,000 deaths as a result of the disease.1,3 By 2030, it is expected that pancreatic cancer could be the second leading cause of cancer death in developed countries.4
Pancreatic cancer remains one of the cancers with the poorest prognosis, with an overall five-year survival rate of less than 5% associated with metastatic disease.5 The most common pancreatic tumors are adenocarcinomas, which account for more than 90% of pancreatic cancer cases.6
The only treatment currently available with curative intent is surgery followed by adjuvant chemotherapy.7 Even if patients are eligible for surgery, the five-year survival rate remains below 10%.6
About Zolbetuximab
Zolbetuximab is a first-in-class monoclonal antibody (mAb) specifically designed to target tumor cells that express CLDN18.2, a transmembrane protein.1
CLDN18.2 is overexpressed in pancreatic cancer, making it a potential therapeutic target.4 The GLEAM trial showed that of patients with metastatic pancreatic cancer, 27.7% overexpressed CLDN18.2 protein in ≥75% of their tumor cells, assessed using an immunohistochemistry assay, which represents a substantial patient group that could potentially benefit from a targeted first-line therapy.1
By binding to CLDN18.2, zolbetuximab induces cancer cell death and tumor growth inhibition by activating two distinct immune system pathways — antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).1.8
Zolbetuximab was the first CLDN18.2 targeted therapy to receive regulatory approval anywhere in the world. Zolbetuximab is the only currently approved treatment for use in CLDN18.2 positive (HER2-negative) gastric or GEJ cancer in a number of countries, including China, the European Union, Japan, and the United States.
About Astellas’ Investigational Pipeline in Pancreatic Cancer
Astellas is evaluating several investigational therapies for the treatment of gastrointestinal cancers, including pancreatic cancer, harnessing multiple novel modalities with the goal of delivering the oncology medicines of tomorrow.
ASP3082 is a selective protein degrader discovered fully in-house that targets mutated KRAS G12D, which is found in approximately 40% of pancreatic ductal adenocarcinomas.8 A potential first-in-class therapy, ASP3082 is currently being evaluated in a Phase 1 clinical trial for patients with metastatic or locally advanced unresectable solid tumors with KRAS G12D mutations. In addition, Astellas is advancing ASP4396 which also targets mutated KRAS G12D and is in Phase 1 study. For more information, visit clinicaltrials.gov with identifier NCT05382559 (ASP3082) or NCT06364696 (ASP4396).
ASP2138 is a bispecific antibody that binds to CD3 and CLDN18.2. It is currently being evaluated in a Phase 1 clinical trial for patients with metastatic or locally advanced unresectable gastric or gastroesophageal junction (GEJ) adenocarcinoma or pancreatic adenocarcinoma whose tumors express CLDN18.2. For more information, visit clinicaltrials.gov with identifier NCT05365581.
Astellas holds a worldwide exclusive license (excluding China’s mainland, Hong Kong, Macao and Taiwan region) to develop and commercialize XNW27011, an investigational antibody-drug conjugate targeting CLDN18.2. XNW27011 is currently being evaluated by Evopoint Biosciences, the licensor of XNW27011, in metastatic or locally advanced solid tumors that express CLDN18.2, including gastric cancer, gastroesophageal cancer and pancreatic cancer. For more information, visit clinicaltrials.gov with identifier NCT06792435.
The safety and efficacy of the agents under investigation have not been established for the uses being considered. There is no guarantee that the agents will receive regulatory approval and become commercially available for the uses being investigated.
About Astellas
Astellas is a global life sciences company committed to turning innovative science into value for patients. We provide transformative therapies in disease areas that include oncology, ophthalmology, urology, immunology and women's health. Through our research and development programs, we are pioneering new healthcare solutions for diseases with high unmet medical need.
References
1 Park W, O’Reilly EM, Li C-P, et al. Zolbetuximab With Gemcitabine + Nab-Paclitaxel (GN) in First-Line Treatment of Claudin 18.2–Positive Metastatic Pancreatic Cancer (mPC): Phase 2, Open-Label, Randomized Study (GLEAM). Poster 1532TiP presented on 14 September 2024 during European Society of Medical Oncology Congress 2024.
2 World Health Organization. International Agency for Research on Cancer Global Cancer Observatory. Pancreas. 2022. Available at: https://gco.iarc.who.int/media/globocan/factsheets/cancers/13-pancreas-fact-sheet.pdf. Accessed October 2025.
3 Li T, Lin C, Wang W. Global, regional, and national burden of pancreatic cancer from 1990 to 2021, its attributable risk factors, and projections to 2050: a systematic analysis of the global burden of disease study 2021. BMC Cancer. 2025 Feb 3;25(1):189.
4 Xu Q, et al. Dark horse target Claudin18.2 opens new battlefield for pancreatic cancer. Front Oncol. 2024. 14. doi.org/10.3389/fonc.2024.1371421.
5 National Cancer Institute, Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Pancreatic Cancer. Available at: https://seer.cancer.gov/statfacts/html/pancreas.html. Accessed October 2025.
6 Sarantis P, Koustas E, Papadimitropoulou A, et al. Pancreatic ductal adenocarcinoma: Treatment hurdles, tumor microenvironment and immunotherapy. World J Gastrointest Oncol. 2020;12(2):173-181
7 Robatel, S, et al. Current limitations and novel perspectives in pancreatic cancer treatment. Cancers (Basel). 2022; 14(4): 985
8 Lee, JK et al. Comprehensive pan-cancer genomic landscape of KRAS altered cancers and real-world outcomes in solid tumors. NPJ Precis Oncol. 2022;9;6(1):91.