FDA Sets Goal Date for Resubmitted Zolbetuximab in Gastric Cancer

The FDA has set a Prescription Drug User Fee Act (PDUFA) action date of Nov. 9, 2024, for the resubmission of the biologics license application (BLA) for zolbetuximab. The agency is reviewing zolbetuximab as a first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma.

In the United States, it is estimated that 26,890 people will be diagnosed with gastric cancer and 10,880 will die from the disease in 2024. These cancers are often diagnosed in the advanced or metastatic stage. The five-year relative survival rate for patients at the metastatic stage is 7%.

Developed by Astellas, zolbetuximab is first-in-class monoclonal antibody that targets and binds to Claudin 18.2 (CLDN18.2), a transmembrane protein. Transmembrane proteins are involved in signal transduction, transport, and protein trafficking, and a study published last year indicated these proteins may contribute to the spread of cancer. Zolbetuximab acts by binding to CLDN18.2 on the cancer cell surface of gastric epithelial cells, which then leads to cancer cell death by activating two distinct immune system pathways.

In January 2024, the FDA issued a complete response letter (CRL) for the zolbetuximab application. The FDA indicated the CRL was because of unresolved deficiencies following its inspection of a third-party manufacturing facility. The BLA was resubmitted on May 9, 2024.

Astella’s application is based on results from the phase 3 SPOTLIGHT and GLOW clinical trials. The SPOTLIGHT study evaluated zolbetuximab plus mFOLFOX6 (a combination regimen that includes oxaliplatin, leucovorin and fluorouracil) compared with placebo plus mFOLFOX6. The GLOW study evaluated zolbetuximab plus CAPOX (a combination chemotherapy regimen that includes capecitabine and oxaliplatin) compared with placebo plus CAPOX.

Results from SPOTLIGHT were published in The Lancet in April 2023. Data from the GLOW study were presented at the March 2023 American Society of Clinical Oncology.