News|Articles|February 6, 2026
Anbenitamab Improves PFS and OS in HER2+ Gastric Cancer
Author(s)Andrea Eleazar, MHS
Fact checked by: Paige Britt
Phase 3 interim data show anbenitamab plus chemo boosts survival and response in previously treated HER2-positive gastric cancer with manageable toxicity.
According to a prespecified interim analysis of the phase 3 KC-WISE/KN026-001 trial (NCT05427383) recently published in Annals of Oncology, the bispecific antibody anbenitamab (KN026) in combination with chemotherapy yielded clinically meaningful survival benefits over chemotherapy alone in patients with previously treated HER2-positive (HER2+) gastric cancer.1
As previously presented at the
Similarly, for overall survival (OS), the median OS was nearly doubled in the anbenitamab arm, reaching 19.6 months (95% CI, 15.0-not evaluable) compared with 11.5 months (95% CI, 6.5-14.4) in the chemotherapy alone group (HR, 0.29; 95% CI, 0.17-0.50; P <.0001).
Secondary efficacy end points also favored the anbenitamab regimen. The objective response rate as assessed by an independent review committee was 56% in the anbenitamab arm vs 11% in the chemotherapy-only arm. The median duration of response was significantly prolonged at 8.2 months with anbenitamab compared with 2.9 months in the control group. Additionally, the disease control rate reached 80% with anbenitamab vs 42% with chemotherapy alone.
Regarding safety, the incidence of treatment-related adverse events (TRAEs) was manageable, though higher in the experimental arm. Grade 3 or higher TRAEs occurred in 60% of patients in the anbenitamab group and 45% of those in the chemotherapy alone group. The most common high-grade toxicities were hematologic, including neutropenia (30% vs 22%) and leukopenia (21% vs 25%). No treatment-related deaths were reported in the anbenitamab group, whereas 5 occurred in the control group.
Notably, cardiac toxicity, a known concern with HER2-targeted therapies, was comparable between groups, with an incidence of 3.2% in both arms.
“These positive findings, along with a favorable safety profile, suggest that anbenitamab in combination with chemotherapy may offer a promising treatment option for these patients,” wrote Liu et al, study authors, in the paper.1 “It thereby establishes a foundation for subsequent head-to-head comparative studies against updated standard regimens, including those containing ramucirumab [Cyramza].”
Anbenitamab is a humanized bispecific antibody that targets 2 distinct, nonoverlapping epitopes of HER2, mimicking the combined activity of trastuzumab (Herceptin) and pertuzumab (Perjeta) but within a single molecule. This dual binding promotes receptor clustering and downregulation, while also enhancing antibody-dependent cellular cytotoxicity. These findings provide robust evidence that dual-epitope targeting via a bispecific approach can overcome resistance to traditional HER2 blockade in the second-line setting for advanced gastric cancer.
About the KC-WISE Trial
Conducted across sites in China, the multicenter, randomized, double-blind phase 2/3 trial was designed to evaluate the safety and efficacy of anbenitamab added to chemotherapy vs placebo and chemotherapy in 188 patients with HER2+ advanced unresectable/metastatic gastric cancer or gastroesophageal junction adenocarcinoma who were refractory to at least 1 previous trastuzumab-containing regimen.2
For treatment, patients were randomly assigned to receive either the anbenitamab at a dose of 30 mg/kg every 2 weeks in combination with investigator’s choice of chemotherapy (n = 95) or chemotherapy alone (n = 93).
REFERENCES
1. 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 1, 2026. doi:10.1016/j.annonc.2026.01.006
2. KN026 in combination with chemotherapy in HER2 positive gastric cancer subjects who have failed first-line therapy. ClinicalTrials.gov. Updated December 19, 2023. Accessed February 6, 2026. https://clinicaltrials.gov/study/NCT05427383
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