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

SPOTLIGHT

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: NCT03504397 · One underlying study; aliases and follow-up publications consolidated.

Phase III, double-blind, placebo-controlled RCT; 565 patients (283 vs 282). Evidence cut-off: 13 November 2026.

Design, population and eligibility

Design / sample size

Phase III, double-blind, placebo-controlled RCT; 565 patients (283 vs 282).

Eligibility

Previously untreated locally advanced unresectable or metastatic HER2-negative, CLDN18.2-positive gastric/GEJ adenocarcinoma; ECOG 0–1.

Intervention

Zolbetuximab + mFOLFOX6 versus placebo + mFOLFOX6.

Zolbetuximab IV plus mFOLFOX6 (oxaliplatin, leucovorin and infusional 5-FU) every 2 weeks; up to 12 cycles of chemotherapy, with study antibody continued per protocol.

Comparator

placebo + mFOLFOX6.

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

Key efficacy outcomes

Median PFS 10.61 vs 8.67 months (HR 0.75, 95% CI 0.60–0.94). OS HR 0.75 (95% CI 0.60–0.94; p=0.0053); median OS not stated here because the cited abstract does not provide it.

Reported outcome

10.61

Comparator: 8.67. 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 87% vs 78%; nausea, vomiting and decreased appetite were prominent; treatment-related deaths approximately 2% vs 1%.

Clinical interpretation and limitations

Independent positive phase III confirmation of zolbetuximab in CLDN18.2-positive disease using a fluoropyrimidine/oxaliplatin backbone. It is not a head-to-head comparison with GLOW; cross-trial median PFS differences must not be used to select CAPOX versus mFOLFOX6.

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.