FDA Sets Action Date for Zolbetuximab for Stomach Cancers

The FDA has accepted and granted priority review for Astellas’ biologics license application (BLA) for zolbetuximab as a first-line treatment of patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma.

In the United States, it is estimated that 26,500 people will be diagnosed with gastric cancer and 11,130 will die from the disease in 2023. These cancers are often diagnosed in the advanced or metastatic stage. The five-year relative survival rate for patients at the metastatic stage is 6.6%.

Moitreyee Chatterjee-Kishore, Ph.D.

“While rare in the United States, gastric cancer can be deadly when diagnosed in the late stages,” Moitreyee Chatterjee-Kishore, Ph.D., senior vice president and head of immuno-oncology development, Astellas, said in a press release.

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 induces cancer cell death by activating two distinct immune system pathways.

The BLA 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 to placebo plus CAPOX.

In the SPOTLIGHT trial, the zolbetuximab arm demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) compared with the placebo arm. Specifically, zolbetuximab reduced the risk of progression or death by 24.9% compared with placebo. Median progression-free survival was 10.61 months in the treatment compared with 8.67 months with placebo.

The incidence of serious treatment-emergent adverse events was similar between both arms and consistent with previous studies. The most frequent adverse events were nausea, vomiting and decreased appetite.

In the GLOW study, zolbetuximab plus CAPOX demonstrated a statistically significant improvement in progression-free survival compared with placebo plus CAPOX. Specifically, the zolbetuximab arm reduced the risk of progression or death by 31.3% compared with placebo plus CAPOX, Median progression-free survival was 8.21 months in the treatment arm and 6.80 months in the placebo arm.

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.