Zolbetuximab is an investigational monoclonal antibody that targets Claudin 18.2 and is used for the treatment of CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma


Astellas Pharma Canada. (Credit: Raysonho@Open Grid Scheduler/Scalable Grid Engine/Wikipedia)

Japanese pharmaceutical company Astellas Pharma has unveiled positive results for its experimental cancer drug Zolbetuximab from the Phase 3 SPOTLIGHT clinical trial.

Zolbetuximab is an investigational monoclonal antibody targeting Claudin 18.2, a transmembrane protein exclusively expressed in multiple cancers.

SPOTLIGHT is a randomised, multi-centre, double-blind, Phase 3 study, which evaluated the efficacy and safety of Zolbetuximab plus mFOLFOX6 (oxaliplatin, leucovorin and fluorouracil) compared to placebo plus mFOLFOX6.

The Phase 3 study enrolled 566 patients with CLDN18.2-positive, HER2-negative, metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

It was conducted at 220 centres in the US, the UK, Australia, Europe, South America, and Asia.

The study has met both, the primary endpoint of showing statistical significance in progression-free survival (PFS), and the secondary endpoint of showing statistical significance in overall survival (OS).

The most frequent treatment-emergent adverse events (TEAEs) in the study include nausea, vomiting, and decreased appetite.

SPOTLIGHT trial primary investigator Kohei Shitara said: “I am excited by the potential for a new treatment option to help patients with advanced-stage gastric cancer or GEJ cancer.

“Gastric and GEJ cancers still have very limited treatment options available for patients with an advanced diagnosis.”

Zolbetuximab works by binding to CLDN18.2 on the cancer cell surface of gastric epithelial cells, which induces the death of the cancer cell by activating antibody-dependent cellular toxicity and complement-dependent cytotoxicity.

The pre-clinical studies on the drug showed that CLDN18.2 may become more exposed and accessible to targeted therapies with antibodies, as gastric tumours develop.

Astellas said that the safety and efficacy of Zolbetuximab are currently being investigated in gastric, gastroesophageal, and pancreatic cancers, and have not been established.

Astellas senior vice president and development therapeutic areas head Ahsan Arozullah said: “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 the development of Zolbetuximab for the first-line treatment of patients with locally advanced or metastatic gastric cancer.

“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.”