Acceptable safety profile and encouraging efficacy of nanvuranlat in BTC

Patients with pre-treated, advanced biliary tract cancer (BTC) may benefit from treatment with nanvuranlat, efficacy data from a phase 2 study indicated. According to the authors, the safety profile was clean. Further, larger studies are needed to establish the efficacy and safety of nanvuranlat in this population.

High expression of LAT1 in tumour specimens has been identified as a predictor of poor prognosis in patients with various cancer types, including BTC [1], explained Dr Junji Furuse (Kanagawa Cancer Center, Japan). Nanvuranlat, a selective LAT1 inhibitor, may therefore improve the situation of patients with BTC. A previous phase 1 trial showed encouraging efficacy data in 5 patients with BTC [2]. The current phase 2 study randomised 104 patients with advanced, refractory BTC with a NAT-2 non-rapid phenotype 2:1 to nanvuranlat, 25 mg/m², 5 days administration followed by 9 days wash-out, intravenous, or placebo [1]. Most patients had received at least 2 previous lines of therapy. The primary endpoint was the progression-free survival (PFS) by blinded independent central review.

Patients treated with nanvuranlat had a significantly improved PFS compared with patients treated with placebo (HR 0.557; 95% CI 0.34–0.90; P=0.016) and this result was consistent across pre-defined subgroups. Furthermore, the disease-control rate appeared to be higher in the experimental arm than in the control arm (24.6% vs 11.4%). In addition, all patients who achieved disease control showed stable disease, except for 1 patient in the nanvuranlat arm who had a partial response.

As for safety, grade 3 or higher adverse event rates were generally low in both arms, not surpassing the 3.0% for a specific event in either study group. However, it seemed that grade 3 or higher cholangitis occurred more frequently in the nanvuranlat arm than in the placebo arm (12.9% vs 0%).

In conclusion, data from the current phase 2 study support further investigation of nanvuranlat in patients with heavily pre-treated advanced BTC.

1. Kaira K, et al. BMC Cancer. 2013;13:482.
2. Okano N, et al. Invest New Drugs. 2020;38(5):1495–1506.
3. Furuse J, 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. Abstract 494, ASCO GI 2023, 19–21 January, San Francisco, CA, USA.

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Posted on 17 March 2023