Anbenitamab combined with chemotherapy significantly prolonged overall survival (OS) and progression-free survival (PFS), tripling response rates compared with chemotherapy alone in patients with previously treated HER2-positive gastric or gastroesophageal junction (GEJ) cancer.

These results from an interim analysis of the KC-WISE trial were presented at the 2025 ESMO Congress by Prof Jianming Xu, MD, Chinese PLA General Hospital, Beijing, China.

In patients with HER2-positive gastric or GEJ cancer who have progressed following trastuzumab-based therapy, effective second-line treatment options remain limited. Anbenitamab (KN026) is a novel HER2-targeted bispecific antibody that binds 2 distinct HER2 epitopes, enhancing receptor blockade and antitumor activity. 

KC-WISE is an ongoing multicenter, randomized, double-blind, phase 3 trial evaluating the efficacy and safety of anbenitamab in combination with chemotherapy vs chemotherapy alone in this population.

Eligible patients with centrally confirmed HER2-positive gastric or GEJ cancer and prior progression on trastuzumab-containing regimens were randomized 1:1 to receive anbenitamab 30 mg/kg or placebo plus chemotherapy. Randomization was stratified by chemotherapy backbone, HER2 expression level, and number of prior treatment lines. 

The primary trial end points were PFS and OS both assessed by an independent review committee. The prespecified interim analysis was conducted with a data cutoff of April 3, 2025.

A total of 188 patients were randomized: 95 to the anbenitamab plus chemotherapy group and 93 to the chemotherapy-alone group. At interim analysis, the combination demonstrated a marked improvement in PFS (median, 7.1 vs 2.7 months; hazard ratio [HR], 0.25; 95% CI, 0.17 to 0.39; P <.0001) and OS (median, 19.6 vs 11.5 months; HR, 0.29; 95% CI, 0.17 to 0.50; P <.00001). The objective response rate was substantially higher with anbenitamab plus chemotherapy (56%) compared with chemotherapy alone (11%), indicating robust tumor activity.

Safety findings were consistent with known profiles of HER2-targeted therapy and cytotoxic agents. Grade ≥3 treatment-related adverse events occurred in 60% of patients in the anbenitamab arm and 45% in the control arm. The most frequent high-grade events were neutropenia (30% vs 22%) and leukopenia (21% vs 25%). Importantly, no treatment-related deaths were observed in the anbenitamab group, compared with 5 in the control group.

These interim results demonstrate that anbenitamab plus chemotherapy provides significant and clinically meaningful improvements in survival outcomes compared with chemotherapy alone in patients with HER2-positive gastric or GEJ cancer who have progressed after trastuzumab. The magnitude of benefit in both PFS and OS supports anbenitamab as a promising new standard of care in the post-trastuzumab setting, pending confirmation from ongoing follow-up and final analysis.

Source:

Zhao J, Liu Y, Chen Y, et al. KN026 in combination with chemotherapy for previously treated HER2-positive gastric or gastroesophageal carcinomas (GC/GEJC): Interim analysis of KC-WISE. Presented at the 2025 ESMO Congress; October 17-21, 2025. Berlin, Germany. LBA78