Dr Pabon on the FDA Approval of Zolbetuximab for CLDN18.2+ Gastric/GEJ Adenocarcinoma

Cindy Medina Pabon, MD, assistant professor, Sylvester Cancer Center, University of Miami; assistant lead, GI Cancer Clinical Research, Gastrointestinal Medical Oncology, University of Miami Health Systems, discusses the clinical relevance of the FDA approval of zolbetuximab-clzb (Vyloy) for patients with locally advanced, unresectable or metastatic, HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are Claudin 18.2 (CLDN18.2) positive.

On October 18, 2024, the regulatory agency approved zolbetuximab in combination with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of eligible patients. Zolbetuximab, a promising new drug, has been studied in the phase 3 SPOTLIGHT (NCT03504397) and GLOW (NCT03653507) trials in patients with metastaticgastric cancer, Pabon begins. SPOTLIGHT researchers evaluated whether combining zolbetuximab with mFOLFOX6 (5-fluorouracil, leucovorin, and oxaliplatin) could enhance patient outcomes in this aggressive cancer type, she reports. Zolbetuximab uniquely targets a biomarker called CLDN18.2, a protein that holds gastric cells together, Pabon says. When abnormally expressed, CLDN18.2 can drive the growth of cancer cells. By targeting this protein, zolbetuximab acts as an antibody, binding to CLDN18.2 and triggering various mechanisms that result in cancer cell death, potentially halting tumor progression, she explains.

The results of the SPOTLIGHT and GLOW trials confirmed that adding zolbetuximab to standard chemotherapy provides a survival advantage over standard chemotherapy alone, supporting the agent’s FDA approval, Pabon expands. This approval marks a meaningful advancement for patients with limited treatment options, offering a more targeted approach than standard chemotherapy alone, she notes. Moreover, the success of zolbetuximab research opens the door to further exploration of CLDN18.2 as a target in gastric cancer, emphasizing the need for precise, biomarker-driven treatments to improve outcomes in challenging-to-manage cancers, according to Pabon.

She continues by stating that this breakthrough inspired a growing number of studies worldwide that are investigating novel methods to target CLDN18.2 more effectively. These advancements align with the field’s shift toward precision oncology, where understanding and targeting specific proteins in tumors provide new avenues for treating patients with cancers that are unresponsive to conventional therapies, Pabon explains. Overall, zolbetuximab brings new hope for patients with metastatic gastric cancer and paves the way for innovative treatments targeting CLDN18.2 in gastric cancer and potentially other cancer types, she concludes.