Dr. Shitara on Zolbetuximab Plus mFOLFOX6 in CLDN18.2+, HER2– Gastric/GEJ Adenocarcinoma

Kohei Shitara, MD, medical oncologist and the chief of the Department of Gastrointestinal Oncology of the National Cancer Center Hospital East in Kashiwa, Japan, discusses the evaluation of the combination of zolbetuximab plus mFOLFOX6 in patients with Claudin 18.2 (CLDN18.2)–positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

The phase 3 SPOTLIGHT trial (NCT03504397) randomly assigned patients to receive the combination of zolbetuximab and mFOLFOX6 (n = 283) or placebo and mFOLFOX6 (n = 282).

Findings presented at the 2023 ASCO Gastrointestinal Cancers Symposium showed that patients treated with the combination experienced a statistically significant improvement in progression-free survival (PFS), meeting the primary end point of the trial, Shitara says. Those treated with zolbetuximab and mFOLFOX6 experienced a median PFS of 10.61 months, compared with 8.67 months for those administered mFOLFOX6 plus placebo (HR, 0.751; 95% CI, 0.589-0.942; P = .0066). Additionally, zolbetuximab plus mFOLFOX6 elicited 12- and 24-month PFS rates of 49% and 24%, respectively, compared with 35% and 15% for mFOLFOX6 plus placebo.

Zolbetuximab plus mFOLFOX6 also produced a statistically significant improvement in overall survival (OS), Shitara explains. The median OS was 18.23 months with zolbetuximab/mFOLFOX6 and 15.54 months with placebo/mFOLFOX6 (HR, 0.750; 95% CI, 0.601-0.936; P = .0053). Notably, as part of the study design, OS was only tested if the PFS benefit with zolbetuximab plus mFOLFOX6 was found to be significant, Shitara says.

To be eligible for enrollment, patients were required to have moderate-to-strong CLDN18 staining in at least 75% of tumor cells, and they needed to have HER2-negative disease. Over the course of the trial, investigators screened more than 2700 patients for CLDN18.2 positivity, and 565 patients were enrolled and randomly assigned to treatment during the study, Shitara says.

Along with the primary end point of PFS, key secondary end points included OS, objective response rate, duration of response, and safety.