On October 18, 2024, the U.S. Food and Drug Administration (FDA) approved zolbetuximab-clzb (Vyloy, Astellas Pharma), a novel treatment for adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma. This approval brings a much-needed new option for patients whose tumors express the CLDN18.2 protein, as identified through an FDA-approved test.
What is Zolbetuximab-Clzb?
Zolbetuximab-clzb is a claudin 18.2 (CLDN18.2)-directed cytolytic antibody that specifically targets cancer cells expressing this protein. By combining zolbetuximab-clzb with fluoropyrimidine and platinum-containing chemotherapy, this new regimen offers improved disease control and survival outcomes for patients with advanced gastric and GEJ adenocarcinoma, a particularly aggressive and challenging cancer.
Who is Eligible for This Treatment?
Patients with HER2-negative gastric or GEJ adenocarcinoma whose tumors are CLDN18.2-positive, as determined by the newly approved VENTANA CLDN18 (43-14A) RxDx Assay, are eligible for treatment with zolbetuximab-clzb. This companion diagnostic ensures that patients receive the most appropriate and effective treatment based on their specific tumor biology.
Efficacy of Zolbetuximab-Clzb: Key Results from Clinical Trials
Two large randomized clinical trials, SPOTLIGHT and GLOW, evaluated the efficacy and safety of zolbetuximab-clzb combined with chemotherapy.
- SPOTLIGHT Trial:
- Patients received either zolbetuximab-clzb with mFOLFOX6 chemotherapy or placebo with mFOLFOX6.
- Progression-Free Survival (PFS): 10.6 months in the zolbetuximab-clzb group vs. 8.7 months in the placebo group.
- Overall Survival (OS): 18.2 months in the zolbetuximab-clzb group vs. 15.5 months in the placebo group.
- These results demonstrate a significant improvement in both PFS and OS, establishing zolbetuximab-clzb as a new standard of care for these patients.
- GLOW Trial:
- Patients received zolbetuximab-clzb with CAPOX chemotherapy or placebo with CAPOX.
- Progression-Free Survival (PFS): 8.2 months in the zolbetuximab-clzb group vs. 6.8 months in the placebo group.
- Overall Survival (OS): 14.4 months in the zolbetuximab-clzb group vs. 12.2 months in the placebo group.
- This trial further confirmed the superior efficacy of the zolbetuximab-clzb regimen in extending survival in patients with advanced disease.
Safety Profile
As with any cancer therapy, adverse reactions are a key consideration. In the clinical trials:
- The most common serious adverse reactions (≥2%) in both trials included vomiting, nausea, neutropenia, febrile neutropenia, and diarrhea.
- Pneumonia, pulmonary embolism, and sepsis were also observed, highlighting the need for close monitoring during treatment.
Despite these side effects, the survival benefits demonstrated in both trials underscore the importance of zolbetuximab-clzb as a promising new treatment for patients with advanced gastric and GEJ adenocarcinoma.
Dosing Information
The recommended dosing regimen for zolbetuximab-clzb includes:
- First dose: 800 mg/m² intravenously.
- Subsequent doses: 600 mg/m² every 3 weeks or 400 mg/m² every 2 weeks in combination with fluoropyrimidine- and platinum-containing chemotherapy.
A New Option for Patients with CLDN18.2-Positive Tumors
Zolbetuximab-clzb represents a significant breakthrough for patients with CLDN18.2-positive gastric or GEJ adenocarcinoma. This targeted therapy, combined with chemotherapy, improves both progression-free and overall survival, offering new hope to patients who previously had limited treatment options. With the approval of the companion diagnostic, clinicians can ensure the right patients receive this innovative therapy, marking a major advancement in the personalized treatment of gastric and GEJ adenocarcinomas.
As with all cancer therapies, it’s essential for patients to have thorough discussions with their healthcare team to understand their treatment options, potential benefits, and risks, and to tailor their treatment to their specific condition.
About the author
Dr. Sajeve Thomas is a distinguished medical professional and a compassionate guide in the field of oncology. With over a decade of dedicated experience as a board-certified medical oncologist/internal medicine specialist, Dr. Thomas has become a trusted expert in the treatment of melanoma, sarcoma, and gastrointestinal conditions. Currently practicing at the renowned Orlando Health Cancer Institute, he brings a wealth of expertise to the complex and challenging world of oncology.