Zolbetuximab shows promise in CLDN18.2-positive advanced gastric, GEJ adenocarcinomas
Zolbetuximab monotherapy exhibits antitumour activity with acceptable tolerability profile in patients with Claudin 18.2 (CLDN18.2)-positive advanced gastric or gastro-oesophageal junction (GEJ) adenocarcinomas, according to the results of a phase IIa trial.
A total of 54 patients with advanced gastric, GEJ or oesophageal adenocarcinomas with moderate-to-strong CLDN18.2 expression in ≥50 percent of tumour cells received zolbetuximab intravenously every 2 weeks for five planned infusions.
These patients were consecutively enrolled in three cohorts. Cohorts 1 (n=4) and 2 (n=6) were small lead-in groups evaluating the feasibility of repeated administration of zolbetuximab monotherapy at two dose levels (300 mg/m2 as safety run-in and 600 mg/m2 as targeted dose). Cohort 3 (n=44) was a larger dose-expansion arm of the 600 mg/m2 dose. Three patients in cohort 1 and 25 patients in cohorts 2 and 3 received at least five infusions.
The primary endpoint was objective response rate (ORR; complete and partial response), while secondary endpoints included clinical benefit (ORR plus stable disease), progression-free survival, safety/tolerability, and zolbetuximab pharmacokinetic profile.
In the overall population, 43 patients had available antitumour activity data. Four patients achieved partial response (ORR, 9 percent) and six (14 percent) had stable disease, yielding a clinical benefit rate of 23 percent.
In the subgroup of patients with moderate-to-high CLDN18.2 expression in ≥70 percent of tumour cells, ORR was 14 percent (n=4/29).
Treatment-related adverse events occurred in 81.5 percent of patients (44 of 54). Commonly reported events were nausea (61 percent), vomiting (50 percent) and fatigue (22 percent).
Zolbetuximab (formerly known as IMAB362) is a first-in-class monoclonal antibody that binds to CLDN18.2 and can induce immune-mediated lysis of CLDN18.2-positive cells. The findings support CLDN18.2 as a target for immune-mediated antitumour therapy and promote further investigation of the drug, specifically in combination with chemotherapy, as a potential treatment for patients with advanced gastric cancer, the researchers said.