Nanvuranlat confers PFS gains in advanced, refractory biliary tract cancer

The investigational L-type amino acid transporter 1 inhibitor nanvuranlat has an acceptable safety profile and is associated with prolonged progression-free survival (PFS) in patients with advanced and refractory biliary tract cancer when used in later-line treatment settings, according to the results of a phase II study.

The study included 105 heavily treated patients who were recruited from 14 Japanese cancer centres and hospitals. These patients were randomly assigned to receive either nanvuranlat 25 mg/m²/day (n=70) or placebo (n=35). Treatment was administered intravenously in cycles of 5 consecutive days, followed by 9 days off.

PFS was the primary endpoint. Overall survival and disease control rates were also evaluated as secondary endpoints. Subgroup analysis was performed according to biliary tract cancer subtypes and among patients with high L-type amino acid transporter 1 expression.

Compared with placebo, nanvuranlat yielded an improvement in PFS (hazard ratio [HR], 0.56, 95 percent confidence interval [CI], 0.34–0.90; p=0.02). This was true among patients with high L-type amino acid transporter 1 expression (HR, 0.44, 95 percent CI, 0.23–0.85).

When analysis was stratified by biliary cancer subtypes, the HRs for the risk of progression or death with nanvuranlat vs placebo was 0.22 (95 percent CI, 0.10–0.49) among patients with extrahepatic cholangiocarcinoma and gallbladder cancer, 0.87 (95 percent CI, 0.44–1.75) among those with intrahepatic cholangiocarcinoma, 0.49 (95 percent CI, 0.29–0.83) among those with intrahepatic and extrahepatic cholangiocarcinoma and gallbladder cancer, and 1.05 (95 percent CI, 0.31–3.53) among those with ampulla of Vater cancer.

Grade 3 or higher adverse events occurred in 30.0 percent of patients in the nanvuranlat group and in 22.9 percent of those in the placebo group.

The overall survival did not significantly differ between nanvuranlat- and placebo-treated patients. Results of an exploratory analysis warrant the evaluation of the long-term clinical benefit of nanvuranlat in patients with intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer.