Anbenitamab Plus Chemotherapy Improves Survival After Trastuzumab in HER2-Positive Gastric and Gastroesophageal Junction Cancer

Clinical Summary: 

• Design/Population: This randomized, double-blind, phase 3 trial evaluated anbenitamab plus chemotherapy versus placebo plus chemotherapy in patients with HER2-positive gastric or gastroesophageal junction (G/GEJ) adenocarcinoma whose disease had progressed following trastuzumab-containing therapy.

• Key Outcomes: At the prespecified interim analysis, anbenitamab plus chemotherapy significantly prolonged progression-free and overall survival compared with chemotherapy alone, reducing the risk of disease progression by 75% and the risk of death by 71%. The regimen demonstrated a manageable safety profile despite a higher incidence of grade ≥3 treatment-related adverse events.

• Clinical Relevance: These findings support anbenitamab plus chemotherapy as a promising second-line treatment strategy for HER2-positive G/GEJ adenocarcinoma following trastuzumab-based therapy.

Results from a phase 3 trial demonstrated that anbenitamab plus chemotherapy significantly improved progression-free and overall survival compared with placebo plus chemotherapy in patients with previously treated HER2-positive gastric or gastroesophageal junction (G/GEJ) adenocarcinoma.

“Anbenitamab is a novel bispecific antibody that simultaneously binds to two distinct HER2 epitopes,” stated Rongyue Liu, MD, PhD, Chinese PLA General Hospital, Beijing, China, and coauthors. “In a phase 2 study, anbenitamab plus chemotherapy demonstrated a favorable efficacy profile in the second-line treatment of HER2-positive metastatic [gastric cancer], directly validating its mechanistic rationale.”

In this multicenter, double-blind trial, 188 patients with HER2-positive G/GEJ adenocarcinoma whose disease had progressed following trastuzumab-based therapy were randomized 1:1 to receive either 30 mg/kg of anbenitamab (n = 95) or placebo (n = 93) in combination with chemotherapy. Chemotherapy consisted of paclitaxel, docetaxel, or irinotecan, with treatment selection determined before randomization. The primary end points were progression-free survival (PFS) and overall survival (OS). Safety was a key secondary end point.

At the prespecified interim analysis, median PFS was 7.1 months with anbenitamab plus chemotherapy compared with 2.7 months with placebo plus chemotherapy, representing a 75% reduction in the risk of disease progression or death (hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.17 to 0.39; P < .0001). Median OS was 19.6 months and 11.5 months, respectively, corresponding to a 71% reduction in the risk of death (HR, 0.29; 95% CI, 0.17 to 0.50; P < .0001).

Grade ≥3 treatment-related adverse events occurred in 60% of patients receiving anbenitamab plus chemotherapy compared with 45% of those receiving placebo plus chemotherapy. The most common grade ≥3 events included neutropenia (30%) and leukopenia (21%). No treatment-related deaths occurred in the anbenitamab arm.

“These positive findings, along with a favourable safety profile, suggest that anbenitamab in combination with chemotherapy may offer a promising treatment option for these patients,” concluded Dr Liu et al. “It thereby establishes a foundation for subsequent head-to-head comparative studies against updated standard regimens, including those containing ramucirumab.” 

Source:

Liu R, Zhao J, Zhang R, et al. Anbenitamab in previously treated HER2-positive gastric cancer (KC-WISE): pre-specified interim analysis of a randomized, phase III clinical trial. Ann Oncol. Published online: January 19, 2026. doi:10.1016/j.annonc.2026.01.006