Data shows investigational zolbetuximab plus CAPOX reduced risk of progression or death by 31.3% vs CAPOX alone
Study evaluated patients with Claudin 18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma
Two statistically significant Phase 3 trials, GLOW and SPOTLIGHT, to serve as the basis for global regulatory submissions
TOKYO, March 22, 2023 – Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., “Astellas”) will present detailed results from the Phase 3 GLOW trial evaluating first-line treatment with zolbetuximab, an investigational first-in-class Claudin 18.2 (CLDN18.2) targeted monoclonal antibody, plus CAPOX (a combination chemotherapy regimen that includes capecitabine and oxaliplatin) versus placebo plus CAPOX in patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.
In the study, investigational treatment zolbetuximab plus CAPOX demonstrated a statistically significant improvement in progression-free survival (PFS) compared to placebo plus CAPOX. Specifically, zolbetuximab plus CAPOX reduced the risk of progression or death by 31.3% (n=507; hazard ratio [HR]=0.687; [95% confidence interval [CI]: (0.544-0.866)]; p=0.0007) compared to placebo plus CAPOX, meeting GLOW’s primary endpoint. Median PFS was 8.21 months (95% CI: 7.46–8.84) in the treatment arm and 6.80 months (95% CI: 6.14–8.08) in the placebo arm.
The study also showed that zolbetuximab plus CAPOX significantly prolonged overall survival (OS), a key secondary endpoint, reducing the risk of death by 22.9% (HR=0.771; 95% CI: 0.615-0.965; p=0.0118). Median OS was 14.39 months (95% CI: 12.29-16.49) and 12.16 months (95% CI: 10.28-13.67) for the treatment arm and placebo arm, respectively.
The incidence of serious treatment-emergent adverse events (TEAEs) was similar between both arms (47.2% versus 49.8% in the zolbetuximab versus placebo arms, respectively) and consistent with previous studies.1 The most frequent TEAEs in the GLOW study were nausea (68.5% versus 50.2%), vomiting (66.1% versus 30.9%) and decreased appetite (41.3% versus 33.7%) in the zolbetuximab versus placebo arms.
“The progression-free and overall survival data from GLOW demonstrate the potential of zolbetuximab in patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric and gastroesophageal junction cancer,” said Rui-Hua Xu, M.D., Ph.D., Professor in the Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China, and the primary investigator of GLOW. “While the treatment landscape is continuing to evolve, patients at this stage of the disease are in need of options and the GLOW data are encouraging for this patient population.”
These detailed results from the GLOW trial will be presented at the March American Society of Clinical Oncology (ASCO) Plenary Series (Wednesday, March 22, 2023, at 4:00 p.m. ET) by Manish A. Shah, M.D., Medical Oncologist and Director of the Gastrointestinal Oncology Program, Weill Cornell Medicine, New York.
“We are committed to the ongoing clinical development of zolbetuximab and to bringing new therapeutic options for patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma,” said Ahsan Arozullah, M.D., M.P.H., Senior Vice President and Head of Development Therapeutic Areas, Astellas. “These two statistically significant Phase 3 trials, GLOW and SPOTLIGHT, will serve as the basis for global regulatory submissions, marking remarkable progress in our gastric cancer development program.”
The GLOW and SPOTLIGHT studies are a part of Astellas’ gastric cancer development program to investigate targeted treatment options such as zolbetuximab and address patient needs in locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. In both trials, approximately 38% of these patients had CLDN18.2-positive tumors (≥75% of tumor cells with strong-to-moderate membranous CLDN18.2 staining intensity), as determined by a validated immunohistochemistry assay.2
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