Zolbetuximab, a new targeted therapy, has just been approved in Singapore to treat certain types of advanced stomach and gastroesophageal cancers, bringing new hope to patients who previously had few options after diagnosis.
In its early stages, gastric cancer can look deceptively harmless – often mistaken for common gastrointestinal discomfort.
Indigestion, bloating, early satiety, and nausea are easily brushed off. But by the time symptoms persist or worsen, many patients are already facing an advanced diagnosis.
What is Gastric and Gastroesophageal Junction (GEJ) Cancer?
Gastric cancer, also known as stomach cancer, develops from the stomach lining. The gastroesophageal junction (GEJ) cancer occurs at the area connecting the oesophagus and the stomach.
Globally, gastric cancer is the fifth most common cancer. In Singapore alone, approximately 300 deaths were reported between 2018 and 2022. The challenge lies in the early symptoms such as indigestion, nausea and stomach discomfort, which are often mistaken for other common digestive issues. As a result, many patients are only diagnosed once the cancer has advanced.
According to Dr Choo Su Pin, Medical Oncologist at Curie Oncology, the average survival rate for the advanced HER2-negative gastric cancer patients is only 10 to 12 months, as they often deteriorate when treatment fails.
Treating Gastric and GEJ Cancer
Surgery can sometimes be curative in patients with early-stage gastric cancer. However, for advanced or metastatic cases, surgery may no longer be a curative option.
Treatment options at this stage are limited. While chemotherapy, targeted therapy, and immunotherapy can help slow the disease, the outcomes are often modest. Palliative care (such as pain relief and nutritional support) also plays a key role in maintaining comfort and quality of life.
Within this difficult reality, a new treatment has arrived, bringing renewed hope for a subset of patients.
Targeting a Specific Mutation: CLDN18.2
Roughly 40% of gastric cancer patients have tumours that express a protein called claudin 18.2 (CLDN18.2). In normal stomach cells, this protein is hidden away. But during cancer development, it becomes exposed on tumour cell surfaces – making it a useful target for drug therapy.
This is where zolbetuximab (VYLOY) comes in.
So, What’s New?
In March 2025, zolbetuximab was approved in Singapore as a first-line treatment for patients with:
- Advanced or metastatic gastric or gastroesophageal junction (GEJ) cancer
- Tumours that are CLDN18.2-positive
- HER2-negative status
Zolbetuximab (VYLOY) is a monoclonal antibody that binds specifically to CLDN18.2 on the surface of cancer cells. Once attached, it helps destroy the malignant cells and inhibit tumour growth through mechanisms called antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity.
“Zolbetuximab is a new class of drug in the treatment of gastric cancer, offering our patients another potentially efficacious treatment option with survival benefits. This adds to the current ammunition that we have in treating gastric cancers,” said Dr Choo.
Clinical Trials That Supported Approval of Zolbetuximab
Zolbetuximab was tested in two large international studies – SPOTLIGHT and GLOW – involving over 1,000 patients in total. Both studies looked at how well the drug worked when added to standard chemotherapy in patients with CLDN18.2-positive gastric or GEJ cancer.
SPOTLIGHT (Phase 3) Trial
SPOTLIGHT trial was a global, randomised and multi-centre study that involved 565 patients across 215 sites in Asia, Australia, and Europe.
All patients received a common chemotherapy regimen called mFOLFOX6 (a mix of leucovorin, fluorouracil, and oxaliplatin). Half were also given zolbetuximab, while the others received a placebo.
Patients who received zolbetuximab saw their cancer take longer to worsen (progression-free survival) – 10.6 months vs 8.7 months in the placebo group.
This means the drug helped slow the spread of cancer when used together with chemotherapy.
GLOW (Phase 3) Trial
The GLOW trial used a slightly different chemotherapy combo – CAPOX (capecitabine and oxaliplatin). The study followed 507 patients, and again compared zolbetuximab + chemotherapy versus chemotherapy alone.
Patients on zolbetuximab had longer progression-free survival: 8.2 months vs 6.8 months. Overall survival was also better: 14.4 months vs 12.2 months with chemotherapy alone.
Across both trials, zolbetuximab consistently reduced the risk of disease progression or death—by around 25–31%. While these gains may seem modest, they can offer valuable extra time to patients and families facing a tough diagnosis.
What This Means for Patients in Singapore
Many patients felt hopeful knowing there is finally a new option for a cancer that historically had few effective treatments. According to Dr Choo, early responses to zolbetuximab have been promising.
“In my experience so far, zolbetuximab has been well tolerated by most patients and allowed them to bring the cancer under control.”
Despite the encouraging feedback from her patients, Dr Choo pointed out a key challenge that may affect how widely the treatment is used: cost.
“The cost of treatment is always a concern, particularly the issue of who will bear it. In Singapore, whether the drug makes it into the Cancer Drug List will determine how often this drug will be prescribed.”
A Step Into the Future of Gastric Cancer Care
Advanced gastric and GEJ cancers remain among the toughest to treat. Zolbetuximab is reshaping how doctors manage gastric cancer for the years ahead. As the first targeted therapy approved for CLDN18.2-positive gastric cancer, it paves the way for more personalised and precise treatment approaches.
“This is the first anti-CLDN18.2 targeted therapy in gastric cancer that has proven efficacious,” said Dr Choo. “It has opened the door to further treatment approaches for gastric cancers that have CLDN18.2 over-expression.”
With better targeting, improved outcomes will follow. The hope is clear that even in difficult diagnoses, there is now one more reason not to give up.
Read More:
- Singapore scientists map tumours for better, more precise treatments in stomach cancer
- NUH Unveils Cutting-Edge Digestive Health Centre for Enhanced Cancer Detection
- Stomach Cancer: An Overview of the Disease
References
- Top 10 Stomach Cancer Myths Debunked. Medical Channel Asia. Updated: 13 November 2024. https://medicalchannelasia.com/top-10-stomach-cancer-myths-debunked/
- National Registry of Diseases Office. Singapore Cancer Registry Annual Report 2022. Accessed: 23/4/2025. https://www.nrdo.gov.sg/publications/cancer
- Shitara, K., et al. (2023) Zolbetuximab plus mFFOX6 in patients with CLDN 18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind phase 3 trial. Lancet (London, England), 401 (10389), 1655-1668. https://pubmed.ncbi.nlm.nih.gov/37068504/
- Shah, M.A., Shitara, K., Ajani, J.A. et al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med 29, 2133–2141 (2023). www.nature.com/articles/s41591-023-02465-7
- Singapore scientists map tumours for better, more precise treatments in stomach cancer. Medical Channel Asia. Updated: 27 March 2025. https://medicalchannelasia.com/singapore-scientists-map-tumours-for-better-more-precise-treatments-in-stomach-cancer/
