According to a phase 2 study, nanvuranlat demonstrated clinical activity in patients with advanced, refractory biliary tract cancer who had previously received chemotherapy or other treatments.

Results from this study were presented on Thursday, January 19, 2023, at the American Society of Clinical Oncologists Gastrointestinal Cancers Symposium in San Francisco, CA, by Junji Furuse, MD, PhD, Kanagawa Cancer Center, Japan.

Overexpression of LAT1 in cancer cells “supports aggressive proliferation” and “high expression of LAT1 in tumor specimens has been identified as a predictor of poor prognosis in patients with various cancer types,” including biliary tract cancers, according to Dr Furuse and coauthors. Nanvuranlat is a first-in-class, single agent that selectively inhibits the L-type amino acide transporter (LAT1).

In this double-blind trial, 106 patients with intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer, and ampulla of Vater cancer were enrolled. Patients were pre-classified as non-rapid acetylators to minimize metabolism of nanvuranlat and were refractory to or intolerant of standard chemotherapy and other investigational medicines. Patients were then randomized on a 2-to-1 basis to receive either 25 mg/m² nanvuranlat for 5 days followed by session for 9 days (n = 70) or placebo (n = 36). The primary end point of this study was progression-free survival (PFS).

The study met its end point, with nanvuranlat demonstrating a statistically significant improvement in PFS compared with placebo (hazard ratio [HR] 0.557; 95% confidence interval [CI], 0.3435 to 0.9029; one-sided P = .0164). The average disease control rate in the nanvuranlat group was 24.6%, compared with 11.4% in the placebo group.

In the nanvuranlat group, 30.0% and 41.4% of patients reported grade 3 adverse events and treatment-related adverse events respectively, compared to 22.9% and 57.1% in the placebo group. There were no adverse events which led to discontinuation, dose reduction, or death in the nanvuranlat group.

Dr Furuse et al concluded, “LAT1 inhibitor monotherapy with nanvuranlat demonstrated useful clinical efficacy in patients with 4 different subtypes of pre-treated, advanced, refractory [biliary tract cancer],” adding that the safety profile was “highly tolerated.”

Source:

Furuse J, Ikeda M, Ueno M, et al. Nanvuranlat, an L-type amino acide 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. Presented at 2023 ASCO Gastrointestinal Cancers Symposium; January 19-21, 2023; San Francisco, CA. Abstract 494