Anbenitamab Plus Chemotherapy After Trastuzumab Failure in HER2-Positive G/GEJ Cancer

Key Clinical Takeaways: 

• Design/Population: This randomized, double-blind, phase 3 trial evaluated anbenitamab plus chemotherapy vs chemotherapy alone in patients with HER2-positive gastric or gastroesophageal junction (G/GEJ) adenocarcinoma whose disease had progressed following trastuzumab-containing therapy.
• Key Outcomes: At a prespecified interim analysis, anbenitamab plus chemotherapy significantly improved progression-free survival and overall survival, reducing the risk of progression and death by approximately 75% and 71%, respectively, compared with chemotherapy alone.
• Clinical Relevance: These findings suggest that anbenitamab combined with chemotherapy may represent a promising treatment strategy for patients with HER2-positive G/GEJ cancer after trastuzumab failure, pending confirmation in the final analysis.

Results from a multicenter, phase 3 trial demonstrated that anbenitamab plus chemotherapy improved survival compared with placebo plus chemotherapy among previously treated patients with 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 double-blind study, 188 patients who experienced disease progression after trastuzumab-based treatment were randomized 1:1 to receive 30 mg/kg of anbenitamab (n = 95) or placebo (n = 93) in combination with chemotherapy (175 mg/m² of paclitaxel or 75 mg/m² docetaxel administered on day 1, or 125 mg/m² of irinotecan administered on days 1 and 8 of each 21-day cycle). Patients were stratified based on chemotherapy regimen, HER2 expression, and number of prior lines of therapy. Primary end points were progression-free survival (PFS) and overall survival (OS), and a key secondary end point was safety.

At the prespecified analysis, median PFS was 7.1 months in the anbenitamab plus chemotherapy arm and 2.7 months in the placebo plus chemotherapy arm (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 (HR, 0.29; 95% CI, 0.17 to 0.50; P <.0001). Grade ≥ 3 treatment-related adverse events occurred in 60% of patients in the anbenitamab plus chemotherapy and 45% of patients in the placebo plus chemotherapy arm. The most frequently reported events included neutropenia (30%) and leukopenia (21%). No treatment-related deaths were reported 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