GLOW
Trial question
What is the role of zolbetuximab plus CAPOX in patients with claudin 18.2-positive gastric or GEJ adenocarcinoma?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
38.0% female
62.0% male
N = 507
507 patients (192 female, 315 male).
Inclusion criteria: patients with claudin 18.2-positive, HER2-, locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma.
Key exclusion criteria: receipt of prior systemic chemotherapy; receipt of radiotherapy in ≤ 14 days before randomization; receipt of treatment with herbal or other treatments that have known anti-tumor activity within 28 days before randomization; receipt of systemic immunosuppressive therapy within 14 days before randomization.
Interventions
N=254 zolbetuximab plus CAPOX (zolbetuximab 800 mg/m² on day 1 of cycle 1 followed by 600 mg/m² on day 1 of subsequent cycles plus oral capecitabine 1,000 mg/m² BID on days 1-14 of each cycle and intravenous infusion of oxaliplatin 130 mg/m² on day 1 of each cycle for eight 21-day cycles).
N=253 placebo plus CAPOX (matching placebo plus oral capecitabine 1,000 mg/m², BID on days 1-14 of each cycle and intravenous infusion of oxaliplatin 130 mg/m² on day 1 of each cycle for eight 21-day cycles).
Primary outcome
Median progression-free survival
8.21 months
6.8 months
8.2 months
6.2 months
4.1 months
2.1 months
0.0 months
Zolbetuximab plus capecitabine and
oxaliplatin
Placebo plus capecitabine and
oxaliplatin
Significant
increase ▲
Significant increase in median progression-free survival (8.21 months vs. 6.8 months; HR 1.45, 95% CI 1.15 to 1.83).
Secondary outcomes
Significant increase in median overall survival (14.39 months vs. 12.16 months; HR 1.3, 95% CI 1.04 to 1.64).
Safety outcomes
No significant difference in grade ≥ 3 treatment-emergent adverse events.
Conclusion
In patients with claudin 18.2-positive, HER2-, locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma, zolbetuximab plus CAPOX were superior to placebo plus CAPOX with respect to median progression-free survival.
Reference
Manish A Shah, Kohei Shitara, Jaffer A Ajani et al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med. 2023 Aug;29(8):2133-2141.
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