Dr. Coveler on the Rationale to Evaluate NUC-3373 in Metastatic CRC

Andrew Coveler, MD, director, Pancreatic Cancer Specialty Clinic, Seattle Cancer Care Alliance, associate professor, Medical Oncology, University of Washington School of Medicine, physician, UW Medicine, and associate professor, Clinical Research Division, Fred Hutchinson Cancer Research Center, discusses the rationale to evaluate NUC-3373 in metastatic colorectal cancer (mCRC).

Currently, 5-fluorouracil (5-FU) remains a standard of care treatment for patients with many gastrointestinal malignancies, including CRC, says Coveler. However, 5-FU confers significant off-target toxicities and has a short half-life. As such, NUC-3733, a targeted inhibitor of thymidylate synthase, was designed to be similar to 5-FU but have higher specificity for TS and potentially more activity, Coveler explains.

During the 2021 Gastrointestinal Cancers Symposium, findings from the phase 1b NuTide:302 study of NUC-3733 in combination with standard therapies in patients with mCRC were presented. The agent demonstrated encouraging efficacy signals, an attractive pharmacokinetic profile, and a tolerable safety profile.

Regulatory indications for NUC-3773 may begin in the later-line settings for patients with mCRC; however, the ultimate objective is to have the agent available for use in all lines of treatment and effectively replace 5-FU as a standard of care, concludes Coveler.