Zolbetuximab is a new drug for the treatment of gastric cancer. In trials, it showed significant improvement in survival rates. The FDA is expected to make an approval decision on the drug in January 2024.

Zolbetuximab is a monoclonal antibody that targets a protein found on cancer cells.

It’s currently under priority Food and Drug Administration (FDA) review, and a decision on whether to approve it is expected in January 2024.

In clinical trials, the drug — when used alongside chemotherapy drugs — showed significant improvements in both progression-free survival and overall survival.

Read on to learn more about zolbetuximab, how it works, its efficacy, its side effects, and who might benefit from the drug.

Zolbetuximab is a monoclonal antibody used as a targeted form of cancer therapy. It targets a type of protein known as CLDN18.2 found on cancerous gastric cells.

Zolbetuximab is the first drug of its kind. If approved, it will be a first-line treatment option for people with HER2-negative gastric cancer, advanced unresectable gastric cancer, metastatic gastric cancer, and gastric cancer or gastroesophageal junction cancer with CLDN18.2 positive tumors.

When gastric tumors develop, the protein CLDN18.2 may appear more exposed on the cancer cell’s surface. This exposure may make it a useful target for drugs like zolbetuximab.

Once zolbetuximab binds to this protein, it causes the cancer cells to die.

Zolbetuximab showed promising results in two phase 3 clinical trials.

In the GLOW trial, zolbetuximab was tested alongside the chemotherapy drug CAPOX. Results from the trial showed the combination of zolbetuximab and CAPOX reduced the risk of progression by 31% and the risk of death by 25%.

Median progression-free survival was 8.21 months for people who received this combination compared with 6.8 months among those who received a placebo plus only CAPOX.

Zolbetuximab plus CAPOX was also found to significantly prolong the overall survival of patients, reducing risk of death by 22.9%.

In the SPOTLIGHT trial, zolbetuximab was tested with the combination chemotherapy regime mFOLFOX6. This combination therapy reduced the risk of progression or death by 24.9%.

The median progression-free survival was 10.61 months with this combination compared with 8.67 months for those who only received a placebo plus mFOLFOX6.

Zolbetuximab may help some people with gastric cancer. Also known as stomach cancer, it’s the fifth most commonly diagnosed cancer globally.

In the United States, roughly 26,500 people will be diagnosed with gastric cancer in 2023 and 11,130 people will die from it.

The rate of gastroesophageal junction adenocarcinomas, a cancer where the esophagus meets the stomach, has increased in the last few decades.

Early stages of gastric cancer often don’t show any symptoms, so by the time gastric cancer or gastroesophageal junction cancers are diagnosed, they often have reached the advanced or metastatic stages.

Research suggests that these forms of cancers have some of the highest unmet medical need.

The overall 5-year survival rate for gastric cancer is 35.7%.

For cancer that is found in the stomach only, known as localized stomach cancer, the 5-year survival rate is 74.7%.

For regional stomach cancer, where the cancer spreads to nearby organs or lymph nodes, the 5-year survival rate is 34.6%.

When the stomach cancer is metastatic and has spread from the stomach to distant organs and areas of the body, the 5-year survival rate is just 6.6%.

Zolbetuximab may help people with:

  • advanced, unresectable gastric cancer
  • metastatic gastric cancer
  • HER2-negative gastric cancer
  • gastric cancer or gastroesophageal junction cancer with CLDN18.2 positive tumors

Zolbetuximab may cause side effects. Both the GLOW and SPOTLIGHT trials showed that the most common side effects were nausea, vomiting, and a decrease in appetite.

In the GLOW trial, 68.5% of those treated with zolbetuximab plus CAPOX experienced nausea, compared with 50.2% of those who were treated with a placebo and CAPOX only.

In addition, 66.1% experienced vomiting, compared with 30.9% in the placebo group, while 41.3% experienced a decrease in appetite compared with 33.7% in the placebo group.

The SPOTLIGHT trials showed similar results for zolbetuximab plus mFOLFOX6. In this dataset, 82.4% of people treated with this combination experienced nausea compared with 60.8% in the placebo plus mFOLFOX6 group.

In addition, 67.4% experienced vomiting compared with 35.6% in the placebo group, and 47% experienced a decreased appetite compared with 33.5% in the placebo group.

Researchers note that nausea experienced in the trials was well managed through antiemetics, adjusting infusion rates, and dose interruptions.

Given this, the trial concluded that the benefit versus risks of zolbetuximab plus chemotherapy was worth it due to the significant survival benefit and the safety profile of the drug.

In July 2023, Astellas, the pharmaceutical company behind zolbetuximab, announced that the FDA had granted zolbetuximab priority review.

A priority review means that the FDA aims to make a decision on the drug within 6 months. Under the standard review process, this may take up to 10 months.

Drugs may be granted priority review if they would provide a significant improvement to the safety or efficacy of treatments, diagnosis, or prevention of serious conditions.

The FDA expects to make a decision about zolbetuximab by January 12, 2024.

If approved, zolbetuximab will be the first ever treatment of its kind for the first-line treatment of certain types of gastric cancer.

People with advanced unresectable gastric cancer, metastatic gastric cancer, HER2-negative gastric cancer, and gastric cancer or gastroesophageal junction cancer with CLDN18.2 positive tumors may benefit from the new drug.

In trials, the drug showed significant improvements in survival rates.

The FDA is expected to make a decision on zolbetuximab in January 2024.