KEY TAKEAWAYS
- The GLOW Study Phase 3 trial aimed to investigate the efficacy and safety of 1L zolbetuximab + CAPOX compared to PBO+ CAPOX in CLDN18.2+, HER2−, or GEJ adenocarcinoma.
- The primary endpoint was to determine PFS. Secondary endpoint was OS.
- Researchers noticed sustained and statistically significant improvements in PFS and OS with 1L zolbetuximab + CAPOX.
The GLOW study, a phase 3 trial, evaluated the efficacy of 1L zolbetuximab + capecitabine + oxaliplatin (CAPOX) compared to placebo (PBO) + CAPOX in PFS (final; median 8.2 vs 6.8 mo, HR 0.69 [95% CI 0.54, 0.87], P = 0.0007) and OS (interim; median 14.4 vs 12.2 mo, HR 0.77 [95% CI 0.62, 0.97], P = 0.0118) in patients (pts) with CLDN18.2+, HER2−, locally advanced (LA) unresectable, or metastatic gastric or gastroesophageal junction adenocarcinoma (mG/GEJ).
Florian Lordick and his team aimed to assess the extended efficacy and safety of the treatment by providing an updated analysis with 8.7 months of additional follow-up from the primary analysis.
The study performed an inclusive analysis where pts were randomly assigned in a 1:1 ratio to receive either zolbetuximab intravenously (IV) at a dose of 800 mg/m2 on cycle 1, day 1, followed by 600 mg/m2 every 3 weeks, in addition to CAPOX (oral capecitabine BID on D1–14 and oxaliplatin IV on D1) for eight 21-day cycles. Alternatively, pts were assigned to receive PBO along with CAPOX. For pts without progressive disease (PD) after cycle 8, the treatment continued with zolbetuximab or placebo, along with capecitabine at the investigator’s discretion, until PD or meeting discontinuation criteria. The primary endpoint assessed was progression-free survival (PFS) according to RECIST v1.1 by independent review committee (IRC), with overall survival (OS) as a key secondary endpoint.
About 507 pts were assigned to either zolbetuximab + CAPOX (n = 254) or PBO + CAPOX (n = 253), at the data cutoff on June 29, 2023. In the zolbetuximab arm vs placebo arm, the median follow-up for PFS was 17.8 months vs. 15.1 months, and for OS, it was 26.1 months vs. 26.2 months, respectively. The median PFS for zolbetuximab vs. PBO was 8.3 months vs. 6.8 months (HR 0.68 [95% CI 0.55, 0.85], P = 0.0004).
The median OS for zolbetuximab vs. PBO was 14.3 months vs. 12.2 months (HR 0.77 [95% CI 0.62, 0.95], P = 0.0079). The 24-month OS rate was 28.3% vs. 18.8%, with ongoing follow-up through final analyses. The most common treatment-emergent adverse events (TEAEs) with zolbetuximab + CAPOX included nausea (zolbetuximab arm: 68.9% vs. placebo arm: 50.2%), vomiting (66.1% vs. 31.3%), and decreased appetite (41.3% vs. 34.5%). Incidences of serious TEAEs were similar between arms (48.0% vs. 50.6%).
The study concluded that zolbetuximab + CAPOX consistently showed statistically significant improvement in both PFS and OS when compared to PBO + CAPOX. Importantly, no new safety signals were identified. These findings provide robust support for considering Zolbetuximab + CAPOX as a compelling and potential new first-line treatment option for pts diagnosed with CLDN18.2+, HER2−, locally advanced unresectable, or mG/GEJ adenocarcinoma.
The study is sponsored by Astellas Pharma Global Development, Inc.
Source: https://cslide.ctimeetingtech.com/asia2023/attendee/confcal/show/session/47
Clinical Trial: https://clinicaltrials.gov/study/NCT03653507
Lordick F, Shah M A, Shitara K, et al. (2023). “Updated efficacy and safety results from phase III GLOW study evaluating zolbetuximab + CAPOX as first-line (1L) treatment for patients with claudin-18 isoform 2-positive (CLDN18.2+), HER2−, locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma” Presented at ESMO ASIA 2023 (Abstract 134MO).
