Anbenitamab in previously treated HER2-positive gastric cancer (KC-WISE): prespecified interim analysis of a randomized, phase III clinical trial.

[BACKGROUND] Gastric cancer after progression on trastuzumab treatment remains an unmet therapeutic challenge and is associated with suboptimal progression-free survival (PFS) and overall survival (OS).

[PATIENTS AND METHODS] This multicenter, randomized, double-blind, phase III trial was conducted at 51 hospital sites in China. Patients with HER2-positive gastric cancer or gastroesophageal junction (GC/GEJ) adenocarcinoma whose previous therapy containing trastuzumab had failed were randomized (1 : 1) to receive anbenitamab 30 mg/kg or placebo every 3 weeks, in combination with chemotherapy (paclitaxel 175 mg/m or docetaxel 75 mg/m on day 1 of a 21-day cycle, or irinotecan 125 mg/m on day 1 and 8 of a 21-day cycle), stratified by combined chemotherapy [taxane (paclitaxel or docetaxel) or irinotecan], HER2 expression [immunohistochemistry (IHC) 3+ or IHC 2+/FISH+], and previous lines of therapy (1 or ≥2). Primary endpoints were independent review committee-assessed PFS and OS in the intention-to-treat population. This interim analysis was planned when ∼120 PFS events were observed.

[RESULTS] A total of 188 patients were enrolled and assigned to receive anbenitamab plus chemotherapy (anbenitamab group, n = 95) or chemotherapy alone (control group, n = 93). At the prespecified interim analysis, anbenitamab plus chemotherapy significantly improved PFS [median 7.1 months, 95% confidence interval (CI) 5.5-10.3 months versus 2.7 months, 95% CI 1.5-3.0 months; hazard ratio (HR), 0.25, 95% CI 0.17-0.39, P < 0.0001] and OS (median 19.6 months, 95% CI 15.0 months to not evaluable versus 11.5 months, 95% CI 6.5-14.4 months; HR 0.29, 95% CI 0.17-0.50, P < 0.0001) compared with chemotherapy alone. Grade 3 or higher treatment-related adverse events occurred in 56 (60%) of 94 patients who received anbenitamab plus chemotherapy and 42 (45%) of 93 patients who received chemotherapy alone, with neutropenia (30% versus 22%) and leukopenia (21% versus 25%) being most common. Treatment-related deaths were reported in 0 and 5 patients in the anbenitamab and control groups, respectively.

[CONCLUSIONS] Compared with chemotherapy alone, anbenitamab plus chemotherapy demonstrated clinically meaningful superior PFS and OS in patients with HER2-positive GC/GEJ adenocarcinoma whose previous therapy containing trastuzumab had failed. These findings warrant confirmation in the final analysis.