Table 2.

Summary of clinical trials of zolbetuximab

NCT/CTR Number	Status	Phase	Enrollment	Target indication population	Arms and interventions	Key inclusion criteria:	Outcome measures	Results summary
NCT01197885	Completed	II	54	International, multicenter, open-label, phase II study in patients with advanced adenocarcinoma of the stomach or the lower esophagus: the MONO study	Experimental: zolbetuximab Cohort 1 repeated doses of 300 mg/m2 Cohort 2 repeated doses of 600 mg/m2	Metastatic,R/R disease of advanced adenocarcinoma of the stomach or the lower esophagus proven by histology CLDN18.2 expression of the biopsy material from the cancer confirmed by IHC At least 1 measurable site of disease according to RECIST criteria	CR, PR	Among the 43 patients with antitumor activity data available, 4 achieved PR (9%), and 6 (14%) had SD, resulting in a clinical benefit rate of 23%. In the patients with CLDN18.2 expression in ≥70% of tumor cells, the ORR was 14% (n = 4/29) [65].
NCT01630083	Completed	II	252	First-line treatment of patients with CLDN18.2-positive advanced adenocarcinomas of the stomach, the esophagus or the GEJ	Active comparator: EOX treatment Experimental: EOX + zolbetuximab 800/600 mg/m2 Experimental: EOX + zolbetuximab 1000 mg/m2	• Histologically confirmed adenocarcinoma of the stomach, the esophagus or the GEJ • Inoperable locally advanced disease or recurrent or metastatic disease. • CLDN18.2 expression confirmed by IHC	PFS	Zolbetuximab plus EOX improved PFS (mPFS 4.8 vs. 7.9 months; HR 0.47; p < .001) and OS (mOS 8.4 vs. 13.2 months; HR 0.51; p < .001) compared to EOX alone. In the subpopulation with CLDN18.2 expression ≥2+ intensity in ≥70% tumor cells, efficacy was more pronounced (mOS 9 vs. 16.7 mo; HR 0.45; p < .001) [67].
NCT03653507 CTR20190261	Recruiting	III	500	First-line treatment of CLDN 18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma: the FAST study	Experimental: Arm A (zolbetuximab plus CAPOX) Placebo comparator: Arm B (placebo plus CAPOX)	Histologically confirmed gastric or GEJ adenocarcinoma. Confirmed locally advanced unresectable or metastatic disease. CLDN18.2+ in ≥75% of tumor cells and HER2-negative	PFS	Both PFS [HR = 0.44; 95% CI, 0.29–0.67; P < 0.0005] and OS (HR = 0.55; 95% CI, 0.39–0.77; P < 0.0005) were significantly improved with zolbetuximab + EOX compared with EOX alone. PFS benefit was retained in patients with CLDN18.2 ≥ 70% of tumor cells (HR = 0.38; 95% CI, 0.23–0.62; P < 0.0005). Significant improvement in PFS in the overall population [11].
NCT03504397 CTR20190258	Recruiting	III	550	First-line treatment of CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma	Experimental: Arm A (zolbetuximab plus mFOLFOX6) Placebo comparator: Arm B (Placebo plus mFOLFOX6)	• Histologically confirmed gastric or GEJ adenocarcinoma. • Locally advanced unresectable or metastatic disease。 • CLDN18.2+ in ≥75% of tumor cells and HER2-negative	PFS	Results are pending.

Abbreviations: GEJ Gastroesophageal junction, GC Gastric cancer, PFS Progression-free survival, HR Harzard ratio, CI Confidence interval, R/R, relapsed or refractory, CR Complete remission, PR Partial remission