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

Screening, Construction, and Preliminary Evaluation of CLDN18.2-Specific Peptides for Noninvasive Molecular Imaging

“…26,27 A recent phase III clinical study published in the journal Lancet showed that zolbetuximab in combination with mFOLFOX6 (modified folinic acid, fluorouracil, and oxaliplatin regimen) achieved statistically significant improvements in progression-free survival (PFS) and overall survival (OS) compared with placebo plus mFOLFOX6. 28 These clinical trials highlight the potential of CLDN18.2 as the next promising target for GC after HER-2. Therefore, the accurate and comprehensive assessment of CLDN18.2 expression levels to maximize the identification and screening of potential beneficiary patients is an urgent issue.…”

“…Zolbetuximab is the first anti-CLDN18.2 antibody that kills tumor cells through antibody-dependent cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) . Both Sahin et al and Türeci et al showed that zolbetuximab demonstrated good tolerability and antitumor activity in patients with advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma expressing CLDN18.2. , A recent phase III clinical study published in the journal Lancet showed that zolbetuximab in combination with mFOLFOX6 (modified folinic acid, fluorouracil, and oxaliplatin regimen) achieved statistically significant improvements in progression-free survival (PFS) and overall survival (OS) compared with placebo plus mFOLFOX6 . These clinical trials highlight the potential of CLDN18.2 as the next promising target for GC after HER-2.…”

Gastroesophageal Oncology Highlights from the European Society for Medical Oncology Annual Meeting 2023

“…Both studies favored the addition of zolbetuximab to SOC, with GLOW (CAPOX backbone) showing a median PFS of 8.3 months (vs. 6.8 months with placebo plus CAPOX; HR 0.68; p = 0.0004) [22,23] and SPOTLIGHT (mFOLFOX6 backbone) revealing a median PFS of 11.0 months (vs. 8.9 months placebo plus mFOLFOX6; HR 0.73; p = 0.0022) [24,25].…”

Recent advances for treatment of upper gastrointestinal malignancy

“…Zolbetuximab, a chimeric monoclonal antibody, can target exposed CLDN18.2 to stimulate antibody dependent cytotoxicity (ADCC) and complement mediated cytotoxicity (CDC). [30][31][32][33] The Phase 2a MONO trial showed safety and efficacy in patients with advanced CLDN18.2-positive upper GI cancers. 30 Thus, the Phase 2 FAST trial sought to determine the safety and efficacy of zolbetuximab combined with epirubicin, oxaliplatin, and capecitabine (EOX).…”

“…31 The Similar to the GLOW trial, the phase 3 SPOTLIGHT trial combined zolbetuximab with standard chemotherapy regimen modified folinic acid, fluorouracil, and oxaliplatin (mFOLFOX6). 32 This randomized, superiority, double-blind trial included 565 patients with HER2-negative, CLDN18. The primary endpoint for the study was PFS, and the secondary endpoints included OS and time to confirmed deterioration, ORR, duration of response (DOR), and safety and tolerability.…”