NUC-1031 Granted Fast Track Designation for Advanced Biliary Tract Cancer

NUC-1031, a drug for the first-line treatment of patients with advanced biliary tract cancer, has been granted fast track designation by the FDA.

NUC-1031 (Acelarin), a drug for the first-line treatment of patients with advanced biliary tract cancer, has been granted fast track designation by the FDA, according to a press release by NuCana plc.1

NUC-131 is currently being studied in the phase 3 NuTide:121 study (NCT04163900), which is comparing the agent in combination to cisplatin and cisplatin in combination with gemcitabine (Gemzar) in patients with advanced biliary tract cancers. The interventional, parallel assignment, single masking trial has an estimated enrollment of 828 participants and an estimated study completion date of December 2023. Primary end points include overall survival and objective response rate. Secondary end points include progression-free survival, duration of response, 12-month survival, 18-month survival, disease control rate, safety and tolerance, maximum observed plasma concentration, area under the plasma concentration-time curve, elimination half-life, and quality of life.2

During the study, patients are randomized 1:1 into the experimental and control arms. During the experimental arm, patients will receive 725 mg/m2 of NUC-1031 in combination with 25mg/m2 of cisplatin on days 1 and 8 of a 21-day cycle. In the control arm, patients will receive 1000mg/m2 of gemcitabine in combination with 25mg/m2 of cisplatin on days 1 and 8 of a 21-day cycle.

In order to participate in the study, patients must be 18 years of age or older, have histologically confirmed adenocarcinoma of the biliary tract, a life expectancy of ≥16 weeks, an ECOG performance status of 0 or 1, adequate biliary drainage with no evidence of ongoing infection, adequate bone marrow, hepatic, and renal function, and must agree to use contraception. Patients who have received prior systemic therapy for advanced or metastatic biliary track cancer, combined or mixed hepatocellular/cholangiocarcinoma, prior treatment with or known hypersensitivity to NUC-1031, symptomatic central nervous system or leptomeningeal metastases, a history of other malignancies, concurrent serious medical conditions, congenital or acquired immunodeficiency, prior exposure to another investigational agent within 28 days prior to randomization, major surgery within 28 days prior to randomization, are pregnant or breastfeeding, or have residual toxicities from prior treatments or procedures that have not regressed to grade ≤1 severity are not eligible to participate.

“We are very pleased that the FDA recognizes the potential of Acelarin to address the significant unmet need of patients with biliary tract cancer,” said Hugh S. Griffith, NuCana’s founder and chief executive officer, in a press release. “We recently announced enrollment of 418 evaluable patients in our Phase III study, which is expected to enable the first interim analysis in the first half of 2022. This has the potential to allow for an accelerated approval of a new drug application (NDA) for Acelarin in the United States. With both fast track and orphan drug designations in place, we look forward to working closely with the FDA in our efforts to gain approval for Acelarin as the first approved front-line treatment option for patients with biliary tract cancer.”

The study is currently recruiting in locations across Arizona, California, Colorado, Florida, Georgia, Illinois, Kansas, Kentucky, Massachusetts, Michigan, Minnesota, New York, North Carolina, Ohio, Pennsylvania, South Carolina, Texas, Washington, and Wisconsin.

REFERENCES:
NuCana receives fast track designation from the U.S. food and drug administration for Acelarin® (NUC-1031) for the treatment of biliary tract cancer. News release. NuCana. September 29, 2021. Accessed September 30, 2021. https://bit.ly/39SbHmO.
Comparing NUC-1031 plus cisplatin to gemcitabine plus cisplatin in patients with advanced biliary tract cancer. ClincalTrials.gov. Accessed September 30, 2021.