Astellas’ Claudin 18.2 Antibody Shows Its Teeth In GEJ Cancer Trial

Japan’s Astellas Pharma has announced positive topline results from the Phase 3 Spotlight trial testing a combination therapy of its anti-Claudin 18.2 (CLDN18.2) antibody, zolbetuximab, in a subgroup of gastroesophageal junction (GEJ) cancer. 

Zolbetuximab is designed for the first-line treatment of patients with advanced forms of gastric or GEJ adenocarcinomas whose tumors express CLDN18.2. Gastric cancer is often diagnosed late when it has advanced or metastasized, and the five-year relative survival rate for patients at that stage is low — approximately 6%.

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Enhancing Progression-Free Survival And Overall Survival 

The Spotlight study enrolled 566 patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma, and compared zolbetuximab in combination with mFOLFOX6 (a combination including oxaliplatin, leucovorin, and fluorouracil) versus placebo and mFOLFOX6.

In the study, zolbetuximab met the primary endpoint of progression-free survival (PFS) for patients as well as a secondary endpoint of overall survival. 

Side effects of zolbetuximab treatment include nausea, vomiting, and decreased appetite. Detailed results will be presented at a future scientific congress and submitted for publication, said Astellas. 

Zolbetuximab binds to CLDN18.2 on the cancer cell surface of gastric epithelial cells. According to preclinical studies, the binding induces cancer cell death by activating antibody-dependent cellular toxicity and complement-dependent cytotoxicity. CLDN18.2 may also become more exposed and accessible to targeted treatments as gastric tumors develop. Astellas says that approximately 38% of screened patients have CLDN18.2-positive tumors. 

“We’re delighted and excited about the positive topline results from the SPOTLIGHT trial of zolbetuximab in combination with mFOLFOX6, and we have increased confidence in advancing development of zolbetuximab for the first-line treatment of patients with locally advanced or metastatic gastric cancer,” said Ahsan Arozullah, MD, M.P.H., Senior Vice President and Head of Development Therapeutic Areas, Astellas. 

“These topline results further support the role of CLDN18.2 as an emerging biomarker in gastric and GEJ cancer. We look forward to presenting the full results at a scientific congress in the near future,” he said.

Data from Spotlight and another Phase 3 trial called Glow, which will evaluate a combination of zolbetuximab plus capecitabine and oxaliplatin (CAPOX) versus placebo plus CAPOX, will serve as the foundation for global regulatory submissions in the gastric and GEJ cancer indications. 

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Joy Lin

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