Skip to content
Bending the Curve Trial by Trial
?

SPOTLIGHT

A Study to Compare Zolbetuximab (IMAB362) and Chemotherapy With Placebo and Chemotherapy in Adults With Gastric Cancer

Phase 3N = 565NCT03504397

Population
Adults with previously untreated, locally advanced unresectable or metastatic, CLDN18.2-positive (at least 75% of tumour cells with moderate-to-strong membranous CLDN18 staining), HER2-negative gastric or gastro-oesophageal junction adenocarcinoma, ECOG performance status 0 or 1.
Design
Global randomised placebo-controlled double-blind phase 3 trial at 215 centres in 20 countries. Patients were randomly assigned 1:1 to zolbetuximab (800 mg/m2 loading dose, then 600 mg/m2 every 3 weeks) plus mFOLFOX6 or placebo plus mFOLFOX6; stratified by region, number of organs with metastases and previous gastrectomy. Primary endpoint: progression-free survival assessed by independent review committee in all randomly assigned patients.
Primary endpoint
PFS
Arms
  • Placebo plus mFOLFOX6 (control, n = 282): Placebo with mFOLFOX6
  • Zolbetuximab plus mFOLFOX6 (experimental, n = 283): Zolbetuximab 800 mg/m2 loading dose then 600 mg/m2 every 3 weeks with mFOLFOX6
People
Shitara K, senior author Ajani JA
PFSHR 0.75 (95% CI 0.60–0.94)Δ median PFS+1.94 monthsOSHR 0.75 (95% CI 0.60–0.94)
Show the numbers
Results reported for SPOTLIGHT
EndpointAnalysisZolbetuximab plus mFOLFOX6Placebo plus mFOLFOX6Effect
PFSAll randomly assigned patientsPFS assessed by independent review committeeprimaryShitara 2023median 10.61 months (8.90–12.48)median 8.67 months (8.21–10.28)HR 0.75 (95% CI 0.60–0.94)P=0.0066Median follow-up for PFS 12.94 months with zolbetuximab and 12.65 months with placebo.
OSAll randomly assigned patientsprimaryShitara 2023——HR 0.75 (95% CI 0.60–0.94)P=0.0053Overall survival is reported in the abstract as a hazard ratio only (no medians); whether it was a prespecified secondary or an interim analysis is not stated in the abstract.
Results reported for SPOTLIGHT
EndpointAnalysisZolbetuximab plus mFOLFOX6Placebo plus mFOLFOX6Effect
PFSAll randomly assigned patientsPFS assessed by independent review committeeprimaryShitara 2023median 10.61 months (8.90–12.48)median 8.67 months (8.21–10.28)HR 0.75 (95% CI 0.60–0.94)P=0.0066Median follow-up for PFS 12.94 months with zolbetuximab and 12.65 months with placebo.
OSAll randomly assigned patientsprimaryShitara 2023——HR 0.75 (95% CI 0.60–0.94)P=0.0053Overall survival is reported in the abstract as a hazard ratio only (no medians); whether it was a prespecified secondary or an interim analysis is not stated in the abstract.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS0.750.6–0.94
OS0.750.6–0.94
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%0510152025Months (modelled)
  • Zolbetuximab plus mFOLFOX6 (experimental)
  • Placebo plus mFOLFOX6 (control)

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

Data table (modelled values)
MonthsZolbetuximab plus mFOLFOX6Placebo plus mFOLFOX6
0100.0%100.0%
763.3%57.1%
1342.8%35.4%
2027.1%20.2%
2717.1%11.5%
Primary publication: Shitara K, Lordick F, Bang YJ, Enzinger P, Ilson D, Shah MA, et al. Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial. Lancet. 2023;401(10389):1655-1668. PubMedDOI

Appears in

Sources

  1. Shitara K, Lordick F, Bang YJ, Enzinger P, Ilson D, Shah MA, et al. Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial. Lancet. 2023;401(10389):1655-1668.

    PubMedDOI