Efficacy and safety of a novel anti-HER2 therapeutic antibody RC48 in patients with HER2-overexpressing, locally advanced or metastatic gastric or gastroesophageal junction cancer: a single-arm phase II study

Abstract

Background: Current treatment options for human epidermal growth factor receptor 2 (HER2)-overexpressing gastric cancer at third-line have shown limited clinical benefit. Further, there is no specific treatment for HER2 immunohistochemistry (IHC) 2+ and fluorescence in-situ hybridization-negative patients. Here, we report the efficacy and safety of a novel anti-HER2 antibody RC48 for patients with HER2-overexpressing, advanced gastric or gastroesophageal junction cancer.

Methods: Patients with HER2-overexpressing (IHC 2+ or 3+), locally advanced or metastatic gastric or gastroesophageal junction cancer who were under at least second-line therapy were eligible and received RC48 2.5 mg/kg alone every 2 weeks. The primary endpoint was the objective response rate (ORR) assessed by an independent review committee. Secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response, time to progression, disease control rate, and safety.

Results: Of 179 patients screened, 125 were eligible and received RC48 treatment. The ORR was 24.8% (95% confidence interval [CI]: 17.5%-33.3%). The median PFS and OS were 4.1 months (95% CI: 3.7-4.9 months) and 7.9 months (95% CI: 6.7-9.9 months), respectively. The most frequently reported adverse events were decreased white blood cell count (53.6%), asthenia (53.6%), hair loss (53.6%), decreased neutrophil count (52.0%), anemia (49.6%), and increased aspartate aminotransferase level (43.2%). Serious adverse events (SAEs) occurred in 45 (36.0%) patients, and RC48-related SAEs were mainly decreased neutrophil count (3.2%). Seven patients had adverse events that led to death were not RC48-related.

Conclusions: RC48 showed promising activity with manageable safety, suggesting potential application in patients with HER2-overexpressing, advanced gastric or gastroesophageal junction cancer who have previously received at least two lines of chemotherapy.

Trial registration: ClinicalTrials.gov NCT03556345.

Keywords: HER2-overexpressing; RC48; antibody-drug conjugate; gastric cancer; phase II clinical trial; third-line therapy.