Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial.
Manish A ShahKohei ShitaraJaffer A AjaniYung-Jue BangPeter EnzingerDavid IlsonFlorian LordickEric Van CutsemJavier Gallego PlazasJing HuangLin ShenSang Cheul OhPatrapim SunpaweravongHwoei Fen Soo HooHaci Mehmet TurkMok OhJung Wook ParkDiarmuid MoranPranob BhattacharyaAhsan ArozullahRui-Hua XuPublished in: Nature medicine (2023)
There is an urgent need for first-line treatment options for patients with human epidermal growth factor receptor 2 (HER2)-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma. Claudin-18 isoform 2 (CLDN18.2) is expressed in normal gastric cells and maintained in malignant G/GEJ adenocarcinoma cells. GLOW (closed enrollment), a global, double-blind, phase 3 study, examined zolbetuximab, a monoclonal antibody that targets CLDN18.2, plus capecitabine and oxaliplatin (CAPOX) as first-line treatment for CLDN18.2-positive, HER2-negative, locally advanced unresectable or mG/GEJ adenocarcinoma. Patients (n = 507) were randomized 1:1 (block sizes of two) to zolbetuximab plus CAPOX or placebo plus CAPOX. GLOW met the primary endpoint of progression-free survival (median, 8.21 months versus 6.80 months with zolbetuximab versus placebo; hazard ratio (HR) = 0.687; 95% confidence interval (CI), 0.544-0.866; P = 0.0007) and key secondary endpoint of overall survival (median, 14.39 months versus 12.16 months; HR = 0.771; 95% CI, 0.615-0.965; P = 0.0118). Grade ≥3 treatment-emergent adverse events were similar with zolbetuximab (72.8%) and placebo (69.9%). Zolbetuximab plus CAPOX represents a potential new first-line therapy for patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or mG/GEJ adenocarcinoma. ClinicalTrials.gov identifier: NCT03653507 .
Keyphrases
- locally advanced
- double blind
- placebo controlled
- phase iii
- squamous cell carcinoma
- rectal cancer
- neoadjuvant chemotherapy
- clinical trial
- phase ii study
- open label
- epidermal growth factor receptor
- phase ii
- radiation therapy
- free survival
- induced apoptosis
- study protocol
- monoclonal antibody
- cell cycle arrest
- tyrosine kinase
- end stage renal disease
- ejection fraction
- healthcare
- chronic kidney disease
- peritoneal dialysis
- advanced non small cell lung cancer
- cell proliferation
- oxidative stress
- randomized controlled trial
- human health
- prognostic factors
- replacement therapy