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Bending the Curve Trial by Trial
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GLOW

A Study of Zolbetuximab (IMAB362) Plus CAPOX Compared With Placebo Plus CAPOX as First-line Treatment of Subjects With Claudin (CLDN) 18.2-positive, HER2-negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (GLOW)

Phase 3N = 507NCT03653507

Population
Patients with CLDN18.2-positive (at least 75% of tumour cells with moderate-to-strong membranous CLDN18 staining by central immunohistochemistry), HER2-negative, previously untreated, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.
Design
Global double-blind randomised phase 3 trial: 507 patients (254 and 253) were randomised 1:1 (block sizes of two) to zolbetuximab plus CAPOX or placebo plus CAPOX. Primary endpoint: progression-free survival by independent review committee; overall survival was a key secondary endpoint, reported at an interim analysis.
Primary endpoint
PFS
Arms
  • Placebo plus CAPOX (control, n = 253): Placebo with capecitabine plus oxaliplatin
  • Zolbetuximab plus CAPOX (experimental, n = 254): Zolbetuximab with capecitabine plus oxaliplatin
People
Shah MA, senior author Xu RH
PFSHR 0.687 (95% CI 0.544–0.866)Δ median PFS+1.41 monthsOSHR 0.771 (95% CI 0.615–0.965)Δ median OS+2.23 months
Show the numbers
Results reported for GLOW
EndpointAnalysisZolbetuximab plus CAPOXPlacebo plus CAPOXEffect
PFSITT (507 randomised)primaryShah 2023median 8.21 monthsmedian 6.8 monthsHR 0.687 (95% CI 0.544–0.866)P=0.0007
OSITT (507 randomised)interimShah 2023median 14.39 monthsmedian 12.16 monthsHR 0.771 (95% CI 0.615–0.965)P=0.0118Key secondary endpoint, reported at the interim analysis (318 of 507 patients had died, per the full text). Grade 3 or higher treatment-emergent adverse events 72.8% with zolbetuximab and 69.9% with placebo (abstract).
Results reported for GLOW
EndpointAnalysisZolbetuximab plus CAPOXPlacebo plus CAPOXEffect
PFSITT (507 randomised)primaryShah 2023median 8.21 monthsmedian 6.8 monthsHR 0.687 (95% CI 0.544–0.866)P=0.0007
OSITT (507 randomised)interimShah 2023median 14.39 monthsmedian 12.16 monthsHR 0.771 (95% CI 0.615–0.965)P=0.0118Key secondary endpoint, reported at the interim analysis (318 of 507 patients had died, per the full text). Grade 3 or higher treatment-emergent adverse events 72.8% with zolbetuximab and 69.9% with placebo (abstract).
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS0.6870.544–0.866
OS0.7710.615–0.965
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%05101520Months (modelled)
  • Zolbetuximab plus CAPOX (experimental)
  • Placebo plus CAPOX (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsZolbetuximab plus CAPOXPlacebo plus CAPOX
0100.0%100.0%
565.6%60.1%
1043.0%36.1%
1528.2%21.7%
2117.0%11.8%
Illustrative — modelled from reported values, not trial data. OS, interim.
0%25%50%75%100%0102030Months (modelled)
  • Zolbetuximab plus CAPOX (experimental)
  • Placebo plus CAPOX (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsZolbetuximab plus CAPOXPlacebo plus CAPOX
0100.0%100.0%
964.8%59.9%
1842.0%35.8%
2727.2%21.5%
3617.7%12.8%
Primary publication: Shah MA, Shitara K, Ajani JA, Bang YJ, Enzinger P, Ilson D, et al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med. 2023;29(8):2133-2141. PubMedDOI

Appears in

Sources

  1. Shah MA, Shitara K, Ajani JA, Bang YJ, Enzinger P, Ilson D, et al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med. 2023;29(8):2133-2141.

    PubMedDOI