Results from the primary completion of a PHASE3 study (NCT03653507) investigating zolbetuximab in combination with CAPOX for advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma were posted on 2022-10-25. The trial demonstrated that zolbetuximab plus CAPOX extended median Progression Free Survival (PFS) to 8.21 months compared to 6.80 months for placebo plus CAPOX, and median Overall Survival (OS) to 14.32 months versus 12.16 months.

Background

Zolbetuximab is an investigational drug targeting the Claudin 18.2 protein, which is found in the tumors of most patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. The drug is designed to activate the body's immune system to attack tumor cells expressing Claudin 18.2. This patient population represents an unmet medical need.

Trial design

The GLOW study (NCT03653507) was a PHASE3 trial enrolling 507 participants with Claudin 18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. It evaluated zolbetuximab plus CAPOX (capecitabine and oxaliplatin) as a first-line treatment, compared to placebo plus CAPOX.

Key results

The trial reported significant improvements in key survival endpoints:

  • Median Progression Free Survival (PFS) was 8.21 months for the zolbetuximab plus CAPOX group compared to 6.80 months for the placebo plus CAPOX group. A Log Rank analysis yielded a Hazard Ratio (HR) of 0.689 (95.0% Confidence Interval: 0.552, 0.86) with a p-value of 0.0005.
  • Median Overall Survival (OS) was 14.32 months for the zolbetuximab plus CAPOX group versus 12.16 months for the placebo plus CAPOX group. A Log Rank analysis showed an HR of 0.763 (95.0% Confidence Interval: 0.622, 0.936) with a p-value of 0.0047.
  • Objective Response Rate (ORR) was 42.5 Percentage of Participants for the zolbetuximab plus CAPOX group and 39.1 Percentage of Participants for the placebo plus CAPOX group (Cochran-Mantel-Haenszel p-value: 0.2219).
  • Median Time to Confirmed Deterioration (TTCD) using Global Health Status (EORTC QLQ-C30) was 9.40 months for zolbetuximab plus CAPOX versus 7.49 months for placebo plus CAPOX (HR: 0.869, 95.0% CI: 0.655, 1.153, p-value: 0.167).

What this means

The GLOW study results indicate that zolbetuximab combined with CAPOX significantly improved Progression Free Survival and Overall Survival for patients with Claudin 18.2-positive, HER2-negative, advanced gastric or GEJ adenocarcinoma. The median PFS extended by 1.41 months and median OS by 2.16 months over chemotherapy alone. These findings suggest zolbetuximab could offer a new first-line treatment option, addressing a critical unmet medical need in this patient population.

Source

This information was sourced from ClinicalTrials.gov, documenting the primary completion results of trial NCT03653507, which were posted on 2022-10-25. The study details are available on clinicaltrials.gov.