Samuel Klempner, MD

Metastatic gastric and gastroesophageal junction (mG/GEJ) adenocarcinoma remains difficult to treat, underscoring the need for more effective treatment options. A phase 2 study led by Samuel Klempner, MD, a medical oncologist at Mass General Brigham Cancer Institute, and co-corresponding author Kohei Shitara at the National Cancer Center Hospital East in Japan, evaluated a novel treatment approach combining zolbetuximab, nivolumab and chemotherapy.

The researchers enrolled metastatic gastric cancer patients with specific tumor characteristics—namely, those with previously untreated Claudin 18.2 (CLDN18.2)‑positive, HER2‑negative disease—and monitored their responses to the combination therapy over time.

The results showed that patients treated with this triplet therapy had a median progression‑free survival (PFS) of nearly 15 months, meaning they lived without their cancer worsening for that period. For patients with high levels of CLDN18.2, median PFS was even longer, at 18 months.

Among gastric cancer patients with high levels of CLDN18.2 and PD-L1 protein expression, the median PFS was an encouraging 24 months. Additionally, about 62% of patients experienced tumor shrinkage.

These findings suggest that this combination therapy may represent a promising first‑line treatment strategy for CLDN18.2-positivemG/GEJ adenocarcinomas. They also provide a foundation for continued research, including the ongoing phase 3 LUCERNA trial, which is evaluating this approach in a broader patient population.

Published in Nature Medicine on March 16, 2026 | Read the paper: “First-line zolbetuximab plus mFOLFOX6 and nivolumab in unresectable CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: a phase 2 trial”

Summary reviewed by: Samuel Klempner, MD, senior author