Astellas Pharma Inc. has announced that its Phase 2 GLEAM trial evaluating zolbetuximab in combination with gemcitabine plus nab-paclitaxel for metastatic pancreatic adenocarcinoma did not meet its primary endpoint of overall survival (OS).
Despite the outcome, the safety profile of the zolbetuximab combination was consistent with known profiles of the individual therapies. Astellas will continue to analyze the trial data, including secondary endpoints and subgroup analyses, and collaborate with investigators to share findings.
Trial Overview
The GLEAM trial enrolled 393 adult patients across 136 global study centers. It focused on patients with CLDN18.2-positive metastatic pancreatic adenocarcinoma, defined by ≥75% of tumor cells showing moderate to strong membranous CLDN18 staining. The randomized, open-label study compared zolbetuximab plus gemcitabine/nab-paclitaxel against the standard gemcitabine/nab-paclitaxel regimen.
Zolbetuximab and CLDN18.2 Targeting
Zolbetuximab is a first-in-class monoclonal antibody targeting CLDN18.2, a transmembrane protein overexpressed in pancreatic cancer. By binding to CLDN18.2, zolbetuximab activates antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), leading to cancer cell death and tumor inhibition.
Although zolbetuximab has received regulatory approval for CLDN18.2-positive gastric and gastroesophageal junction (GEJ) cancers in several countries, its efficacy in pancreatic cancer remains under investigation.
Pancreatic Cancer Landscape
Pancreatic cancer is among the most lethal malignancies, with a five-year survival rate below 5% for metastatic disease. It is the 12th most common cancer globally and the sixth leading cause of cancer-related death. By 2030, it is projected to become the second leading cause of cancer death in developed nations.
Adenocarcinomas account for over 90% of pancreatic cancer cases. Surgery followed by chemotherapy remains the only curative option, though survival rates remain low even for operable cases.
Astellas’ Broader Oncology Pipeline
Astellas is advancing a diverse pipeline targeting gastrointestinal cancers, including:
- ASP3082 and ASP4396: Investigational therapies targeting KRAS G12D mutations, found in ~40% of pancreatic ductal adenocarcinomas.
- ASP2138: A bispecific antibody targeting CD3 and CLDN18.2.
- XNW27011: An antibody-drug conjugate targeting CLDN18.2, licensed from Evopoint Biosciences.
These agents are in early-phase trials and have not yet received regulatory approval.
Commitment to Innovation
Dr. Moitreyee Chatterjee-Kishore, Head of Oncology Development at Astellas, reaffirmed the company’s dedication to pancreatic cancer research, acknowledging the challenges of treating this aggressive disease and expressing gratitude to trial participants.
The financial impact of the GLEAM trial results on Astellas’ fiscal year ending March 2026 is expected to be minimal.
For more details, visit clinicaltrials.gov and search for Identifier NCT03816163.
