The LAT1 inhibitor nanvuranlat improves progression-free survival (PFS), compared with placebo, in heavily pretreated patients with advanced biliary tract cancer, according to research presented at the 2023 ASCO Gastrointestinal Cancers Symposium.

Patients with biliary tract cancer have been shown to have worse survival if they have high LAT1 expression, explained study presenter Junji Furuse, MD, PhD, of Kanagawa Cancer Center in Yokohama, Japan.

With this in mind, Dr Furuse and colleagues tested the LAT1 inhibitor nanvuranlat in a phase 2 trial of patients with advanced, refractory biliary tract cancer and a NAT-2 nonrapid phenotype.

Continue Reading

The 104 patients were randomly assigned to receive nanvuranlat (n=69) or placebo (n=35). Nanvuranlat was given at 25 mg/m2 daily for 5 days, followed by 9 days of rest.

The patients had intrahepatic cancer (40% in the nanvuranlat arm and 49% in the placebo arm), gallbladder cancer (23% and 23%, respectively), extrahepatic cancer (21% and 17%), and ampulla of Vater cancer (16% and 11%).

Most patients in each arm had metastatic disease (93% in the nanvuranlat arm and 91% in the placebo arm), about half of patients had undergone primary resection (52% and 51%, respectively), and less than half had received at least 3 prior lines of therapy (39% and 40%). Patients in the nanvuranlat arm were more likely to be older than 65 years of age, compared with patients in the placebo arm (65% and 46%, respectively).

Nanvuranlat significantly improved PFS compared with placebo (hazard ratio [HR], 0.557; 95% CI, 0.3435-0.9029; P =.0164). PFS favored nanvuranlat across subgroups, though most differences between the placebo and nanvuranlat arms were not statistically significant.

Significant improvements in PFS were observed among nanvuranlat recipients with extrahepatic cancer (HR, 0.150; 95% CI, 0.0437-0.5153), those with gallbladder cancer (HR, 0.287; 95% CI, 0.1009-0.8183), and those who had undergone primary resection (HR, 0.432; 95% CI, 0.2197-0.8491).

The disease control rate (DCR) was 24.6% among nanvuranlat recipients and 11.4% among placebo recipients. One patient in the nanvuranlat arm had a partial response, and 16 patients had stable disease. Four patients in the placebo arm had stable disease.

The DCR with nanvuranlat was highest among patients with gallbladder cancer (31.3%), followed by ampulla of Vater cancer (27.3%), intrahepatic cancer (22.2%), and extrahepatic cancer (20.0%).

The safety profile of nanvuranlat was comparable to that of placebo, Dr Furuse said. Grade 3 or higher adverse events occurring in more than 1 patient in the nanvuranlat arm were cholangitis (n=9), anemia (n=2), hypertension (n=2), and malignant neoplasm progression (n=2).

Disclosures: This research was supported by J-Pharma Co., Ltd. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Furuse J, Ikeda M, Ueno M, et al. Nanvuranlat, an L-type amino acid transporter (LAT1) inhibitor for patients with pretreated advanced refractory biliary tract cancer (BTC): Primary endpoint results of a randomized, double-blind, placebo-controlled phase 2 study. ASCO GI 2023. January 19-21, 2023. Abstract 494.