Table 2 Summary of clinical trials of zolbetuximab

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.