Clin Cancer Res. 2024 Jul 26. doi: 10.1158/1078-0432.CCR-24-0461. Online ahead of print.
ABSTRACT
PURPOSE: To evaluate the efficacy and safety of nanvuranlat (a LAT1 inhibitor) monotherapy as a later-line treatment in advanced, metastatic, and refractory BTCs.
PATIENTS AND METHODS: The multicenter, randomized, double-blind, placebo-controlled, phase II study was conducted across 14 leading Japanese cancer centers and hospitals. Nanvuranlat 25 mg/m2/day or placebo was given intravenously in cycles of five consecutive days, followed by nine days off. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and disease control rate (DCR). Subgroup analysis was performed in patients with high LAT1 expression and BTC-subtypes.
RESULTS: A total of 211 patients were screened, 105 eligible patients were randomized, and then 70 received nanvuranlat and 35 received placebo. Nanvuranlat demonstrated an improvement in PFS when compared to placebo (Hazard Ratio (HR) 0.56; 95% CI, 0.34 – 0.90; P = 0.02). Grade 3 or higher adverse events were reported in 30.0% and 22.9% of those in the nanvuranlat and placebo groups, respectively. The overall survival (OS) was not statistically different between nanvuranlat- and placebo-treated patients. An exploratory analysis indicated that nanvuranlat is warranted to evaluate its long-term clinical benefit in patients with intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer.
CONCLUSION: Compared with placebo, nanvuranlat improved PFS in patients with advanced and refractory BTC with an acceptable safety profile. Further studies of this promising compound are warranted in the population of patients who are exhausted from treatment options.
PMID:39058429 | DOI:10.1158/1078-0432.CCR-24-0461
