Zolbetuximab Combo Meets Efficacy End Points in CLDN18.2+, HER2- Gastric/GEJ Cancers

The combination of zolbetuximab, capecitabine, and oxaliplatin (CAPOX) met its primary end point of statistical significance in progression-free survival (PFS) compared with placebo plus CAPOX in patients with gastric cancer, according to findings from the phase 3 GLOW trial (NCT03653507).¹

Zolbetuximab is an investigational first-in-class Claudin-18.2 (CLDN18.2) targeted monoclonal antibody. The agent is being evaluated as a first-line treatment option for patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Results announced in a press release by Astellas Pharma Inc also revealed that the studies secondary end point of overall survival (OS) was met, showing statistical significance in patients who were administered zolbetuximab plus CAPOX vs placebo plus CAPOX.

"We are extremely pleased to share positive topline results from GLOW following the positive SPOTLIGHT readout last month. This further confirms the potential role of zolbetuximab in gastric cancer treatment, an important milestone in our gastric cancer development program," said Ahsan Arozullah, senior vice president and head of development therapeutics, in the press release.

The phase 3, global, multicenter, double-blind, randomized, GLOW trial is investigating the efficacy of zolbetuximab plus CAPOX compared with placebo plus CAPOX as first-line treatment for patients with gastric cancers.² A total of 507 patients have been enrolled and administered either zolbetuximab as a minimum 2-hour intravenous (IV) infusion with oxaliplatin as a 2-hour IV infusion and oral capecitabine twice daily or the same regimen with placebo instead of zolbetuximab.

Patients included in the study are aged 18 years and older with a histologically confirmed diagnosis of gastric or GEJ adenocarcinoma, radiologically confirmed locally advanced unresectable or metastatic disease within 28 days before time of randomization, radiologically evaluable disease, a tumor expressing CLDN18.2 in 75% or more tumor cells, a HER2-negative tumor, an ECOG performance status 0 or 1, and a life expectancy of 12 weeks or greater.

Female patients are eligible to enroll in the trial if they is not pregnant and must agree not to breastfeed or donate ova between the time of screening, throughout the study period, and for 6 months after the last administration of the study treatment.

Then, male patients with female partner(s) of childbearing potential must use contraception during the treatment period until 6 months after the final study treatment administration and must agree to not donate sperm during this time. Those with a pregnant or breastfeeding partner must stay abstinent or use a condom for the duration of the pregnancy or time the partner is breastfeeding through the final study treatment administration.

The primary end point of the trial is PFS with secondary end points including OS, objective response rate, time to confirmed deterioration in participant-reported physical functioning and global health status/quality of life, health related quality of life, duration of response, safety and tolerability measured by adverse events, pharmacokinetics, and to determine the immunogenicity profile of zolbetuximab.

The GLOW study is ongoing at 165 study locations and is estimated to be completed on August 31, 2024.

REFERENCES:

1. Astellas announces positive results from phase 3 trial of zolbetuximab combination in gastric cancer. News release. Astellas Pharma Inc. December 15, 2022. Accessed December 19, 2022. https://bit.ly/3HMSh4V

2. A study of zolbetuximab (IMAB362) plus CAPOX compared with placebo plus CAPOX as first-line treatment of subjects with claudin (CLDN) 18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma (GLOW). ClinicalTrials.gov. Updated December 14, 2022. Accessed December 19, 2022. https://clinicaltrials.gov/ct2/show/NCT03653507