Astellas Pharma Inc. has announced positive topline results from the phase 3 GLOW clinical trial evaluating the efficacy and safety of zolbetuximab in combination with CAPOX (a combination chemotherapy regimen that includes capecitabine and oxaliplatin).
Zolbetuximab is an investigational first-in-class claudin-18.2 (CLDN18.2) targeted monoclonal antibody, for the first-line treatment of patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.
The GLOW study met its primary endpoint showing statistical significance in progression-free survival (PFS) for patients treated with zolbetuximab plus CAPOX compared to placebo plus CAPOX. In addition, the study met a key secondary endpoint, overall survival (OS), showing statistical significance for patients treated with zolbetuximab plus CAPOX compared to placebo plus CAPOX. The most frequent treatment-emergent adverse events (TEAEs) were nausea and vomiting. Detailed results will be presented at a future scientific congress and submitted for publication.
An important milestone in Astellas’ gastric cancer program
“Zolbetuximab has the potential to be an innovative therapeutic option for patients with locally advanced unresectable or metastatic gastric or GEJ cancer, a difficult disease for which treatment options are still limited,” said Ruihua Xu, primary investigator for the GLOW study and professor in the Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China.
“I am so pleased with the topline results from GLOW that establish progression-free survival and overall survival in patients treated with zolbetuximab plus CAPOX.”
“We are extremely pleased to share positive topline results from GLOW following the positive SPOTLIGHT readout last month. This further confirms the potential role of zolbetuximab in gastric cancer treatment, an important milestone in our gastric cancer development program,” said Ahsan Arozullah, senior vice president and head of development therapeutic areas, Astellas.
“We intend to discuss these results with regulatory authorities as we continue to develop zolbetuximab for the first-line treatment of patients with locally advanced unresectable or metastatic gastric and GEJ cancer.”
How Zolbetuximab works
Zolbetuximab acts by binding to CLDN18.2 on the cancer cell surface of gastric epithelial cells. In pre-clinical studies, this binding interaction then induces cancer cell death by activating two distinct immune system pathways – antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).
CLDN18.2 is a type of transmembrane protein found in normal gastric cells and is a major component of epithelial tight junctions controlling the flow of molecules between cells.
Pre-clinical studies have shown that CLDN18.2, which is frequently present in gastric tumors, may become more exposed and accessible to targeted antibodies as gastric tumors develop. Based on the SPOTLIGHT and GLOW studies, approximately 38% of these patients have CLDN18.2-positive tumors.
The studies are part of Astellas’ gastric cancer development program to investigate new treatment options such as zolbetuximab and address patient needs in locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma.
Gastric cancer is often diagnosed in the advanced or metastatic stage, or once it has spread from the tumor’s origin to other body tissues or organs. The five-year relative survival rate for patients at the metastatic stage is approximately 6%.