Zolbetuximab Combo Meets PFS End Point in CLDN18.2+ HER2– Advanced/Metastatic Gastric/GEJ Cancer

First-line zolbetuximab (IMAB362) plus capecitabine and oxaliplatin (CAPOX) met the primary end point of progression-free survival (PFS) in patients with Claudin 18.2 (CLDN18.2)–positive, HER2-negative locally advanced unresectable or metastatic gastric or gastroesophageal (GEJ) adenocarcinoma compared with placebo and CAPOX, according to a press release on topline results from the phase 3 GLOW trial (NCT03653507).¹

Zolbetuximab with CAPOX also demonstrated a statistically significant improvement in overall survival (OS) compared with placebo plus CAPOX. The most frequent treatment-emergent adverse effects (TEAEs) observed in the trial included nausea and vomiting.

Investigators of the trial will submit detailed results for publication and present findings at a future scientific meeting.

“Zolbetuximab has the potential to be an innovative therapeutic option for patients with locally advanced unresectable or metastatic gastric or GEJ cancer, a difficult disease for which treatment options are still limited,” primary investigator Ruihua Xu, MD, PhD, a professor of the Department of Medical Oncology at Sun Yat-Sen University Cancer Center in Guangzhou, China, said in the press release. “I am so pleased with the topline results from GLOW that establish PFS and OS in patients treated with zolbetuximab plus CAPOX.”

The global, multi-center, double-blind, randomized study assessed the efficacy and safety of zolbetuximab and CAPOX compared with placebo plus CAPOX among patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. Study investigators enrolled 507 patients across 165 locations across the United States, Canada, United Kingdom, Europe, South America, and Asia.

Patients in the experimental arm received zolbetuximab and oxaliplatin as intravenous infusions for at least 2 hours along with capecitabine taken orally twice a day. Patients in the comparator arm received matched placebo with the same CAPOX backbone.

Secondary end points of the GLOW trial included OS, objective response rate, duration of response, safety and tolerability, and health-related quality of life measured by patient responses using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire.

Patients and 18 years and older with a histologically confirmed diagnosis of gastric or GEJ adenocarcinoma and radiologically confirmed locally advanced unresectable or metastatic disease within 28 days before study treatment were eligible to enroll on the study. Additional inclusion criteria included having radiologically evaluable disease, CLDN18.2 expressed in at least 75% of tumor cells, a HER2-negative tumor, an ECOG performance status of 0 or 1, and a life expectancy of 12 weeks or more.

Topline results from the phase 3 GLOW study followed a positive readout of the phase 3 SPOTLIGHT study (NCT03504397) in November 2022 assessing zolbetuximab plus modified 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) in patients with CLDN18.2-positive HER2-negative advanced/metastatic gastric/GEJ adenocarcinoma.² The study met its primary end point of PFS.

“We are extremely pleased to share positive topline results from GLOW following the positive SPOTLIGHT readout last month,” Ahsan Arozullah, MD, MPH, senior vice president and head of Development Therapeutics Areas of Astellas, concluded.

References

1. Astellas announces zolbetuximab meets primary endpoint in phase 3 GLOW trial as first-line treatment in Claudin 18.2 positive, HER2-negative locally advanced unresectable or metastatic gastric and gastroesophageal junction (GEJ) cancers. News release. Astellas. December 15, 2022. Accessed December 20, 2022. bit.ly/3jkOlhu
2. Astellas announces zolbetuximab meets primary endpoint in phase 3 SPOTLIGHT trial as first-line treatment in Claudin 18.2 positive, HER2-negative locally advanced or metastatic gastric and gastroesophageal junction (GEJ) cancers. News release. Astellas Pharma Inc. November 17, 2022. Accessed December 20, 2022. bit.ly/3EFTdWQ