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 , 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 . 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 . 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.
- Kaira K, et al. BMC Cancer. 2013;13:482.
- Okano N, et al. Invest New Drugs. 2020;38(5):1495–1506.
- 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.
Copyright ©2023 Medicom Medical Publishers
« Combination botensilimab plus balstilimab demonstrates promising activity in heavily pre-treated MSS CRC Next Article
IMbrave 151 missed primary endpoint in advanced BTC »
Table of Contents: ASCO GI 2023
Letter from the Editor
ASCO GI 2023 Highlights Podcast
Oesophageal and Gastric Cancer
Zolbetuximab plus mFOLFOX6 successful in CLDN18.2-positive subgroup of gastric cancer
Regorafenib offers survival benefit for patients with pre-treated gastric cancer
Radiotherapy or not in locally advanced oesophageal or junctional cancer?
Neoadjuvant immunotherapy is safe and efficacious in a phase 2 gastric cancer trial
S-1 adjuvant chemotherapy: 4 or 8 courses in stage 2 gastric cancer?
LATG/LAPG demonstrates excellent long-term efficacy in stage 1 gastric cancer
3-year follow-up data confirms benefits of nivolumab plus chemotherapy
Long-term results for nivolumab plus chemotherapy and nivolumab plus ipilimumab in oesophageal cancer
Promising phase 2 results for HER-Vaxx in gastric cancer
Anal and Colorectal Cancer
IMbrave 151 missed primary endpoint in advanced BTC
Combination botensilimab plus balstilimab demonstrates promising activity in heavily pre-treated MSS CRC
Mutation-based selection to identify patients suitable for panitumumab treatment
Fucoidan associated with quality-of-life benefits in patients with rectal cancer receiving CCRT
ctDNA appears useful in monitoring patients with anal cancer undergoing CRT
SUNLIGHT trial meets primary endpoint in refractory metastatic CRC
Does cell-free DNA influence MRD testing in post-operative colon cancer?
OPERA: surgery may be avoided with adequate therapy in rectal cancer
Can we improve total neoadjuvant therapy for rectal cancer?
Palliative radiation therapy improves hepatic pain in HCC and liver metastasis
Improved survival following postoperative sorafenib plus TACE in HCC
Quality-of-life benefits for tislelizumab in uHCC
Stereotactic body radiation therapy beneficial for patients with locally advanced HCC
SWOG 1815, first-ever phase 3 trial in BTC, fails
Acceptable safety profile and encouraging efficacy of nanvuranlat in BTC
First-line NALIRIFOX superior to standard treatment in mPDAC
Novel approach delivers quality-of-life benefits for patients with pancreatic cancer
Phase 2 abemaciclib trial in patients with advanced NETs