Zolbetuximab-clzb is marketed as Vyloy, a CLDN18.2-targeted monoclonal antibody for first-line treatment of advanced HER2-negative CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma with fluoropyrimidine- and platinum-based chemotherapy. It is FDA approved.
Four biomarkers—MMR, HER2, PD-L1, and Claudin 18.2—are now validated for advanced esophageal cancer, guiding immunotherapy and targeted treatment decisions. Checkpoint inhibitors show clear benefit in MSI-H and PD-L1-positive subgroups, with long-term survival observed. NCCN guidelines recommend broad testing to personalize therapy.
VYLOY (zolbetuximab-clzb) remains the only approved CLDN18.2-targeted therapy for first-line HER2-negative gastric or gastroesophageal junction adenocarcinoma with CLDN18.2-positive tumors. The pipeline is focused on next-generation antibodies, ADCs, CAR-T, NK-cell and bispecific approaches aiming to build on zolbetuximab benchmark data.
Over 20 pharmaceutical companies are developing therapies for HER2-positive gastric cancer, with multiple Phase III trials launched in March 2026 testing novel combination treatments for advanced disease.
New ASCO guideline emphasizes biomarker-driven treatment for advanced gastroesophageal cancer, recommending upfront testing for HER2, PD-L1, MSI/MMR, and CLDN18.2 to guide immunotherapy and targeted therapy selection.
| NCT ID | Title | Status | Phase |
|---|---|---|---|
| NCT07723534 |
Zolbetuximab With mFOLFOX6 or CAPOX in Claudin 18.2 Overexpressed Advanced or Metastatic Biliary Tract Cancers |
NOT_YET_RECRUITING | PHASE2 |
| NCT07680569 |
Phase Ib/IIa Open-label Study, to Evaluate Safety, Tolerability, and Antitumor Activity of HCB101 in Combination With Multiple Agents in Subjects With Advanced Gastric or Gastro-esophageal (GEJ) Adenocarcinoma |
NOT_YET_RECRUITING | PHASE1/PHASE2 |
| NCT07431281 |
Sonesitatug Vedotin in Combination With Capecitabine With or Without Rilvegostomig in Participants With Advanced or Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma Expressing Claudin18.2 |
RECRUITING | PHASE3 |
| NCT07290985 |
AACR Adaptive Biomarker-Driven Organ Preservation Trial in Gastroesophageal Adenocarcinomas |
RECRUITING | PHASE2 |
| NCT06962137 |
Phase II RAINSPOT: Zolbetuximab-Paclitaxel-Ramucirumab for CLDN18.2 Positive Gastro-esophageal Cancer |
RECRUITING | PHASE2 |
| NCT06902545 |
A Study to Observe the Safety of VYLOY (Zolbetuximab) in People in South Korea With Gastric or Gastroesophageal Junction Cancer. |
RECRUITING | |
| NCT06901531 |
A Study of Zolbetuximab Together With Pembrolizumab and Chemotherapy in Adults With Gastric Cancer |
RECRUITING | PHASE3 |
| NCT06881017 |
Establishment of Precision Targeted Therapy Strategies for Advanced Gastric Cancer Based on Novel Molecular Subtyping |
NOT_YET_RECRUITING | PHASE2 |
| NCT06732856 |
A Phase Ib/II Trial of Neoadjuvant Zolbetuximab Plus Docetaxel, Oxaliplatin and S-1 Chemotherapy in Patients With Locally Advanced Gastric Cancer |
RECRUITING | PHASE1/PHASE2 |
| NCT06468280 |
Synergistic Effects of PD-1 Antibody and Chemotherapy/Targeted Therapy Followed by Surgery-centric Local Treatment in Patients With Limited-metastatic Gastric Cancer |
RECRUITING | PHASE2 |
