Astellas' Vyloy Fails Phase 2 Pancreatic Cancer Trial Despite Gastric Cancer Success
Key Insights
Astellas' Claudin18.2 (search)-targeting antibody Vyloy failed to meet its primary endpoint of overall survival in the 393-patient phase 2 GLEAM trial for first-line metastatic pancreatic adenocarcinoma (search).
The study compared Vyloy combined with gemcitabine and nab-paclitaxel against chemotherapy alone, marking Astellas' sole phase 2 venture outside gastric cancer (search) for this drug.
Despite the setback, Astellas maintains a robust pancreatic cancer pipeline including the T-cell engager ASP2138 and Claudin18.2 (search)-directed ADC ASP546C (search) in ongoing trials.
Astellas Pharma's Claudin18.2 (search)-targeting monoclonal antibody Vyloy (zolbetuximab) has failed to demonstrate improved overall survival in patients with metastatic pancreatic adenocarcinoma (search), dealing a significant blow to efforts to expand treatment options for one of the most challenging cancers to treat.
The 393-patient phase 2 GLEAM study compared Vyloy in combination with chemotherapy (gemcitabine and nab-paclitaxel) against chemotherapy alone but failed to meet its primary endpoint of overall survival. This marks a disappointing outcome for a disease that represents the third most common cause of cancer death in developed countries and has one of the lowest survival rates among all solid tumor types.
Clinical Context and Unmet Need
Pancreatic cancer presents extraordinary therapeutic challenges, with locally advanced or metastatic disease accounting for approximately 80% of cases due to the absence of reliable screening tests for early detection. For patients with advanced disease, the median survival time is just five months, and patients experience highly debilitating symptoms throughout their disease course.
The GLEAM trial represented Astellas' sole phase 2 foray outside gastric cancer (search) for Vyloy, according to OncologyPipeline data. The failure underscores the notorious difficulty in treating pancreatic cancer, despite the drug's success in other indications.
Continued Pipeline Development
Despite the setback, Astellas maintains its commitment to pancreatic cancer research through multiple investigational approaches. Moitreyee Chatterjee-Kishore, Astellas' head of oncology development, emphasized the company's dedication to advancing innovative treatments for this challenging disease.
"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," Chatterjee-Kishore stated. "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."
The company is advancing several Claudin18.2 (search)-targeting assets in pancreatic cancer beyond Vyloy. A phase 1 first-line pancreatic cancer trial is ongoing, testing Vyloy in combination with mFolfirinox (search), a different chemotherapy regimen.
Next-Generation Claudin18.2 Approaches
Astellas is particularly focused on ASP2138, a T-cell engager targeting Claudin18.2 (search), which is currently in phase 1 trials for both gastric and pancreatic cancers. In pancreatic cancer specifically, the company is testing ASP2138 as monotherapy in relapsed disease and in combination with mFolfirinox (search) in the front-line setting. Additionally, a phase 1 study is evaluating ASP2138 in neoadjuvant pancreatic cancer followed by adjuvant chemotherapy.
The company also has ASP546C (search), a Claudin18.2 (search)-directed antibody-drug conjugate (ADC) originated from Evopoint (search), in a phase 1/2 solid tumor trial that includes pancreatic cancer patients.
Data on ASP2138 in gastric, gastroesophageal junction, and pancreatic cancers will be presented at the upcoming ESMO cancer conference.
Commercial Success in Gastric Cancer
Despite the pancreatic cancer disappointment, Vyloy continues to demonstrate strong commercial performance in its approved indication. The drug is FDA-approved as part of a chemotherapy combination for first-line treatment of adults with locally advanced or metastatic HER2 (search)-negative, Claudin18.2 (search)-positive gastric or gastroesophageal junction adenocarcinoma (search), specifically in patients with 75% or higher Claudin18.2 expression.
Vyloy remains the only approved Claudin18.2 (search)-targeted therapy on the market and has shown encouraging commercial uptake since launch. Sales reached just over JPY 12.2 billion (approximately $80 million) in the last fiscal year, with an additional JPY 14 billion generated in the first three months of fiscal 2025 alone. According to Astellas, the drug has made an "exceptional start exceeding expectations."
Analysts have projected that Vyloy could eventually achieve annual sales of $1 billion or more, though reaching those levels will depend on widespread adoption of CLDN18.2 testing, which is not routinely performed at present.
Astellas acquired zolbetuximab through its 2016 takeover of Ganymed Pharma (search), paying approximately $430 million upfront in a deal valued at up to $1.3 billion total.