Gastric and Gastroesophageal Junction Cancer · Medical · Advanced / Metastatic · First-line HER2-negative, CLDN18.2-positive unresectable/metastatic disease

GLOW

Clinical question: In first-line her2-negative, cldn18.2-positive unresectable/metastatic disease, does the investigational strategy improve clinically meaningful outcomes versus its control?

Registry: NCT03653507 · One underlying study; aliases and follow-up publications consolidated.

Phase III, double-blind, placebo-controlled RCT; 507 patients (254 vs 253). Evidence cut-off: 13 November 2026.

Design, population and eligibility

Design / sample size

Phase III, double-blind, placebo-controlled RCT; 507 patients (254 vs 253).

Eligibility

Previously untreated locally advanced unresectable or metastatic HER2-negative gastric/GEJ adenocarcinoma with CLDN18.2 positivity by trial assay.

Intervention

Zolbetuximab + CAPOX versus placebo + CAPOX.

Zolbetuximab IV with CAPOX; capecitabine 1000 mg/m² twice daily days 1–14 and oxaliplatin 130 mg/m² day 1 every 3 weeks (up to 8 cycles); zolbetuximab/placebo continued per protocol.

Comparator

placebo + CAPOX.

Primary endpoint: PFS by blinded independent review; OS key secondary endpoint.

Key efficacy outcomes

Median PFS 8.21 vs 6.80 months (HR 0.687, 95% CI 0.544–0.866; p=0.0007). Median OS 14.39 vs 12.16 months (HR 0.771, 95% CI 0.615–0.965; p=0.0118). 12-month PFS 35% vs 19%; 24-month PFS 14% vs 7%; 24-month OS 29% vs 17%.

Reported outcome

8.21

Comparator: 6.80. The bars are a simple display of the first reported pair only; consult the endpoint and time horizon above.

Safety and treatment delivery

Grade ≥3 TEAEs 72.8% vs 69.9%; grade ≥3 vomiting 12.2% vs 3.6%, nausea 8.7% vs 2.4%. Grade 5 TRAEs 2.4% vs 2.8%.

Clinical interpretation and limitations

Positive biomarker-selected phase III evidence. The absolute landmark gains are clinically interpretable; prominent early nausea/vomiting require prophylaxis and counselling. Do not extrapolate to CLDN18.2-negative or HER2-positive disease.

Interpret the reported hazard ratios in the context of the prespecified endpoint, statistical hierarchy, follow-up maturity, crossover/subsequent therapy and enrolled population. Median survival differences are not risk differences and must not be converted into NNT.

Absolute effect

No NNT/NNH is displayed unless an absolute event-risk difference at a clearly stated fixed timepoint can be calculated from reported trial data. Median survival differences and hazard ratios alone do not support an NNT. The visual above uses reported outcome data only.

Primary publication and follow-up

Primary publication

Registry / follow-up / authoritative source

Source-level verification status: primary publication identified and key quoted outcomes transcribed; where full-text toxicity or procedural details were not available, the page explicitly flags the limitation rather than inferring values.

Current-practice context · 13 November 2026

This page separates historical trial results from contemporary practice. Verify the applicable jurisdictional guideline, regulatory approval, biomarker assay, liver function, comorbidity and treatment availability before applying the evidence. NCCN Guidelines Insights are not a substitute for the full NCCN guideline.

Guideline/regulatory reconciliation and browser-rendered QA remain scheduled for the subsequent quality-control pass.