NuCana’s retooled chemotherapy candidate Acelarin has come up short in phase 3 again. The latest failure wipes out hopes that NuCana’s attempt to improve on gemcitabine, sold by Eli Lilly as Gemzar, will drive improved outcomes in biliary cancer.
Scotland-based NuCana used the phosphoramidate chemistry approach that underpins Gilead Sciences' hepatitis C drug Sovaldi to try to address the limitations of gemcitabine. By modifying the molecule, NuCana aimed to get gemcitabine into cancer cells independently of nucleoside transporters and protect the drug from breakdown. In doing so, the biotech expected to overcome cancer drug resistance mechanisms.
That theory has wilted under the harsh glare of late-phase trials. An investigator-initiated phase 3 trial in metastatic pancreatic cancer screeched to a halt after a futility analysis in 2019. Now, NuCana has cut its phase 3 biliary cancer trial short after failing a futility test at the first interim analysis.
The independent data monitoring committee found Acelarin was unlikely to improve overall survival by 2.2 months or more compared to standard of care—gemcitabine plus cisplatin—and, as such, concluded the trial was on course to fail. The phase 3 trial was the only active study of Acelarin, but NuCana is yet to give up, with the team still evaluating the data “to determine future potential development pathways.”
NuCana has two other candidates in the clinic, NUC-3373 and NUC-7738. While the candidates use the same ProTide technology as Acelarin, NuCana emphasized that they are based on different molecules and have distinct modes of action. The company expects to dose the first colorectal cancer patients in a phase 3 clinical trial of NUC-3373 this year.
The failure of Acelarin comes amid a period of change in the long-stagnant biliary cancer market. Earlier this year, AstraZeneca linked its checkpoint inhibitor Imfinzi to improved survival, prompting PCI Biotech to scrap its rival program in the belief it may struggle to complete the trial now that the standard of care has improved.