Adding zolbetuximab to standard frontline chemotherapy can improve outcomes in certain patients with gastric or gastroesophageal junction (GEJ) adenocarcinoma, according to research presented at the 2023 ASCO Gastrointestinal Cancers Symposium.

The phase 3 SPOTLIGHT study showed that adding zolbetuximab to treatment with folinic acid, fluorouracil, and oxaliplatin (mFOLFOX6) improved progression-free survival (PFS) and overall survival (OS) in patients with CLDN18.2-positive, HER2-negative, advanced gastric/GEJ adenocarcinoma.

“These results support zolbetuximab plus mFOLFOX6 as a new potential standard of care,” said study presenter Kohei Shitara, MD, of National Cancer Center Hospital East in Kashiwa City, Chiba, Japan. 

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Dr Shitara noted that zolbetuximab targets CLDN18.2, a tight junction protein that may become exposed on the surface of gastric/GEJ adenocarcinoma cells. The SPOTLIGHT trial ( Identifier: NCT03504397) tested zolbetuximab in patients with previously untreated, CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric/GEJ adenocarcinoma.

A total of 565 patients were randomly assigned to receive zolbetuximab plus mFOLFOX6 (n=283) or placebo plus mFOLFOX6 (n=282). Zolbetuximab was given at 800 mg/m2 on day 1 of the first cycle, at 600 mg/m2 on day 22 of the first cycle, and at 600 mg/m2 every 3 weeks thereafter. mFOLFOX6 was given every 2 weeks for four 42-day cycles. 

Patients without progressive disease could continue zolbetuximab or placebo in combination with folinic acid and fluorouracil beyond 4 cycles until disease progression or discontinuation criteria were met. 

The study’s primary endpoint was PFS. The median PFS was significantly longer with zolbetuximab than with placebo — 10.61 months and 8.67 months, respectively (hazard ratio [HR], 0.751; 95% CI, 0.598-0.942; P =.0066). The 12-month PFS rate was 49% in the zolbetuximab arm and 35% in the placebo arm. The 24-month PFS rate was 24% and 15%, respectively.

The median OS was significantly longer with zolbetuximab than with placebo as well —18.23 months and 15.54 months, respectively (HR, 0.750; 95% CI, 0.601-0.936; P =.0053). The 12-month OS rate was 68% in the zolbetuximab arm and 60% in the placebo arm. The 24-month OS rate was 39% and 28%, respectively.

Response rates and duration of response were similar between the treatment arms. The overall response rate was 60.7% in the zolbetuximab arm and 62.1% in the placebo arm. The median duration of response was 8.51 months and 8.11 months, respectively.

The rate of grade 3 or higher treatment-emergent adverse events (AEs) was 86.7% in the zolbetuximab arm and 77.7% in the placebo arm. The most common treatment-emergent AEs (in the zolbetuximab and placebo arms, respectively) were nausea (81.0% vs 60.8%), vomiting (64.5% vs 34.5%), and decreased appetite (47.0% vs 33.5%). 

The overall incidence of serious treatment-emergent AEs was 44.8% in the zolbetuximab arm and 43.5% in the placebo arm. The rate of fatal treatment-related AEs was 1.8% and 1.4%, respectively.

Disclosures: This research was supported by Astellas Pharma Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Shitara K, Lordick F, Bang Y-J, et al. Zolbetuximab + mFOLFOX6 as first-line (1L) treatment for patients (pts) with claudin-18.2+ (CLDN18.2+) / HER2− locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma: Primary results from phase 3 SPOTLIGHT study. ASCO GI 2023. January 19-21, 2023. Abstract LBA292.