On 20 September 2024, the European Commission approved zolbetuximab in combination with chemotherapy to treat advanced and metastatic Gastric and Gastroesophageal Junction (G/GEJ) cancers. It is the first and only therapy approved in the European Union to target claudin 18.2.

Approximately 38% of patients with advanced Gastric Cancer have tumours that express the claudin (CLDN)18.2 biomarker. Claudin 18.2 is a protein found in many gastric cancer cells, and new treatments target it to help attack the cancer without harming healthy cells. Zolbetuximab is one such treatment; it represents a significant advancement in personalised cancer treatment, as it specifically targets tumour cells that express this biomarker. By binding to CLDN18.2 on the tumour cell membranes, zolbetuximab initiates a biological process that leads to cell death, thereby slowing tumour growth. It is intended to be used in combination with fluoropyrimidine- and platinum-containing chemotherapy.

Two key clinical trials, SPOTLIGHT and GLOW, have tested zolbetuximab in patients with CLDN18.2-positive tumours. Involving over 1,000 participants worldwide, these trials demonstrated that the drug significantly extends both Progression-Free Survival (PFS) and Overall Survival (OS) compared to placebo and other treatments. The trials also reported positive outcomes regarding Quality of Life (QoL), safety and tolerability, and response rates.

The European Commission’s approval aligns with the latest ESMO Gastric Cancer living guidelines, which now recommend zolbetuximab in combination with chemotherapy as a first-line treatment for patients with CLDN18.2-positive and HER2-negative tumours.

Currently, the five-year survival rate for people with G/GEJ cancer is only 26%. The approval of zolbetuximab offers new hope for patients, promising longer survival and an improved Quality of Life.

References:

Shitara, K., Lordick, F., Bang, Y. J., Enzinger, P., Ilson, D., Shah, M. A., … & Ajani, J. A. (2023). Zolbetuximab plus mFOLFOX6 in patients with CLDN18. 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. The Lancet, 401(10389), 1655-1668.

Shah, M. A., Shitara, K., Ajani, J. A., Bang, Y. J., Enzinger, P., Ilson, D., … & Xu, R. H. (2023). Zolbetuximab plus CAPOX in CLDN18. 2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nature medicine, 29(8), 2133-2141.

Author:
Natasha Muench