Trial results for zolbetuximab in advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma were posted on ClinicalTrials.gov on 2025-02-26. The Phase 3 study demonstrated that zolbetuximab combined with mFOLFOX6 chemotherapy significantly extended median progression-free survival (PFS) to 11.04 months compared to 8.94 months with placebo plus chemotherapy, and median overall survival (OS) to 18.23 months versus 15.57 months.
Background
Zolbetuximab (also known as IMAB362) is an investigational drug being studied for the treatment of locally advanced unresectable or metastatic gastric adenocarcinoma and gastroesophageal junction (GEJ) adenocarcinoma. The drug is designed to target the Claudin 18.2 protein, which is commonly found in tumors of this type. By attaching to Claudin 18.2, zolbetuximab is thought to activate the body's immune system to combat the tumor.
Trial design
The Phase 3 study (NCT03504397) enrolled 565 adult participants with locally advanced unresectable or metastatic gastric adenocarcinoma or gastroesophageal junction (GEJ) adenocarcinoma. Participants were randomized to receive either zolbetuximab in combination with mFOLFOX6 chemotherapy (oxaliplatin, folinic acid, and fluorouracil) or placebo along with mFOLFOX6 chemotherapy.
Key results
Key results from the study include:
- Progression-Free Survival (PFS): The median PFS was 11.04 months for the zolbetuximab plus mFOLFOX6 group, compared to 8.94 months for the placebo plus mFOLFOX6 group. This difference was statistically significant, with a Hazard Ratio (HR) of 0.734 (95% Confidence Interval: 0.591, 0.91; p-value: 0.0024).
- Overall Survival (OS): Patients treated with zolbetuximab plus mFOLFOX6 achieved a median OS of 18.23 months, versus 15.57 months in the placebo group. The HR for OS was 0.784 (95% Confidence Interval: 0.644, 0.954; p-value: 0.0075), indicating a significant improvement.
- Time to Confirmed Deterioration (TTCD) Using Physical Functioning (EORTC QLQ-C30): The median TTCD for physical functioning was 9.89 months for the zolbetuximab group and 12.32 months for the placebo group. The HR was 1.295 (95% Confidence Interval: 0.994, 1.687; p-value: 0.028).
- Time to Confirmed Deterioration (TTCD) Using Global Health Status (EORTC QLQ-C30): The median TTCD for global health status was 15.44 months for the zolbetuximab group compared to 11.83 months for the placebo group. The HR was 1.142 (95% Confidence Interval: 0.874, 1.492; p-value: 0.1685).
- Objective Response Rate (ORR): The ORR was 48.1 percentage of participants in the zolbetuximab group and 47.5 percentage of participants in the placebo group. This outcome did not show a statistically significant difference (p-value: 0.4536).
What this means
The statistically significant improvements in both median Progression-Free Survival and Overall Survival suggest that zolbetuximab, when added to mFOLFOX6 chemotherapy, offers a meaningful clinical benefit for patients with locally advanced unresectable or metastatic gastric and GEJ adenocarcinoma. While the Time to Confirmed Deterioration for physical functioning was shorter in the zolbetuximab arm, the overall survival benefit and a trend towards improved global health status indicate a complex profile. The similar Objective Response Rates suggest that the survival benefits may stem from prolonged disease control rather than an increased initial tumor shrinkage rate.
Source
The trial results were posted on ClinicalTrials.gov, a public registry and results database of clinical studies, on 2025-02-26. The information for study NCT03504397 is available on clinicaltrials.gov.