Anbenitamab/Chemo Improves PFS/OS in HER2+ GC/GEJ Adenocarcinoma

Anbenitamab plus chemotherapy yielded favorable clinical outcomes compared with chemotherapy alone in patients with HER2-positive gastric cancer or gastroesophageal junction (GC/GEJ) adenocarcinoma who previously progressed on trastuzumab (Herceptin)-containing therapy. These results from the progression-free survival (PFS) interim analysis of the phase 2/3 KC-WISE trial (NCT05427383) were published in Annals of Oncology.

In this analysis, the median follow-up time was 9.7 months (95% CI, 7.2-11.9) in the anbenitamab group and 9.8 months (95% CI, 7.4-12.9) in the chemotherapy alone group. At those follow-ups, the median independent review committee (IRC)-assessed PFS was 7.1 months (95% CI, 5.5-10.3) vs 2.7 months (95% CI, 1.5-3.0), respectively (HR, 0.25; 95% CI, 0.17-0.39; P <.0001). In the anbenitamab group, the estimated 6-, 9-, and 12-month PFS rates were 54%, 39%, and 24%, compared with 12%, 4%, and 0% in the control group.

Across all prespecified subgroups, these findings were consistent except for among patients with immunohistochemistry (IHC) 2+/fluorescence in situ hybridization (FISH)+ (HR, 0.59; 95% CI, 0.26-1.34). Of patients who had only received one prior line of treatment, those with anbenitamab had a median PFS of 7.1 months (95% CI, 4.3-10.3) vs 2.8 months (95% CI, 1.5-3.0) with chemotherapy alone (HR, 0.29; 95% CI, 0.19-0.44).

The median overall survival (OS) was 19.6 months (95% CI, 15.0-not evaluable [NE]) in the anbenitamab group 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). The estimated 15-, 18-, and 24-month OS rates in the anbenitamab group were 70%, 66%, and 47%, compared with 35%, 28%, and NE in the chemotherapy alone group.

The IRC-assessed objective response rate (ORR) was 56% with anbenitamab vs 11% with chemotherapy alone, and the disease control rate (DCR) was 80% vs 42%, respectively. The median duration of response (DOR) was 8.2 months (95% CI, 4.9-9.9) with the anbenitamab regimen and 2.9 months (95% CI, 1.7-NE) with chemotherapy.

“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 lead author Rongyue Liu, of the senior department of Oncology at Chinese PLA general Hospital in Beijing, China, with coauthors, in the study. “It thereby establishes a foundation for subsequent head-to-head comparative studies against updated standard regimens, including those containing ramucirumab.”

As of April 3, 2025, 188 patients were enrolled in the trial, of whom 95 were randomly assigned to the anbenitamab group and 93 to the control group. Patients received either anbenitamab at 30 mg/kg or placebo every 3 weeks, and, in both groups, chemotherapy consisted of paclitaxel, docetaxel, or irinotecan.

Eligible patients were 18 years or older with histopathologically or cytologically confirmed locally advanced, recurrent, or metastatic GC/GEJ adenocarcinoma that was HER2 positive, defined as IHC 3+, or IHC 2+/FISH+. All patients had also progressed on prior treatment with trastuzumab plus chemotherapy. At least one assessable lesion at baseline per RECIST v1.1, an ECOG performance status of 0 or 1, and a left ventricle ejection fraction (LVEF) of 50% or more were also required for enrollment.

The primary end points of the trial were PFS and OS assessed by IRC. Secondary end points included ORR, DOR, DCR, and safety.

Grade 3 or higher treatment-related adverse effects (TRAEs) occurred in 60% of the anbenitamab group and 45% of the control group. The most common were neutropenia (30% vs 22%, respectively), leukopenia (21% vs 25%), and anemia (18% vs 11%). Further, serious TRAEs occurred in 26% vs 23%, respectively.

Further, AEs of interest occurred in 3 patients in the anbenitamab group, of which 2 were grade 2 decreases in LVEF and 1 was a grade 3 decrease in LVEF. Two of the 3 cases had improved or been alleviated by data cutoff.

Dose reductions, treatment interruptions, and treatment discontinuations due to TRAEs occurred in 44%, 45%, and 11% of the anbenitamab group, and 31%, 32%, and 2% of the control group. Zero patients and 5 patients died due to TRAEs in each respective group.

References

Liu R, Zhao J, Zhang R, et al. Anbenitamab in previously treated HER2-positive gastric cancer (KC-WISE): prespecified interim analysis of a randomized, phase III clinical trial. Ann Oncol. Published online January 19, 2025. doi:10.1016/j.annonc.2026.01.006