NuCana's retooled chemo drug comes up short in pancreatic cancer phase 3

NuCana believes its retooled versions will be free from the membrane transport, activation and breakdown issues that can make cancer resistant to the products on which they’re based. (Pixabay)

NuCana pulled off its $100 million Nasdaq debut on the promise of its reformulated cancer meds, including a version of Eli Lilly’s Gemzar the company hopes will replace the veteran chemotherapy in some cancers. But that drug has hit a snag in its lead indication: pancreatic cancer. 

The cancer center carrying out a phase 3 study in metastatic pancreatic cancer has stopped enrolling patients after an independent committee deemed the trial unlikely to succeed. The site had recruited 200 patients to compare Gemzar to NuCana’s reformulated version, Acelarin. Of those 200 patients, 25 have received or are still undergoing treatment with Acelarin. 

In a planned futility analysis, the committee concluded that the study was not likely to hit its primary objective: beating Gemzar at lengthening patients' lives by at least 42%. The investigators will follow the 25 patients who have already been dosed and will allow patients who are doing well on Acelarin to continue treatment, NuCana said in a statement. 


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Daniel Palmer, the chief investigator of the study, pointed out the difficulty of treating pancreatic cancer—which is often a death sentence—as well as “unfavorable prognostic factors” that disproportionately affected patients receiving Acelarin in the study. 

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“In particular, 54% of the patients in the Acelarin arm were diagnosed at the most advanced stage T4, compared to 36% of patients in the gemcitabine arm.  We need to allow the data to mature and conduct additional analyses, including biomarker assessment, in order to determine the most appropriate course of action,” said Palmer, director of the Liverpool Experimental Cancer Medicine Centre, in the statement. 

Despite the trial’s failure, Palmer and NuCana are optimistic the data might reveal certain patient subgroups faring better than others. 

“We are encouraged by the positive survival trends in the various sub-group analyses and are committed to working with Professor Palmer and the wider study team to determine the optimal path forward for this study,” said NuCana CEO Hugh Griffith in the statement. 

In addition to pancreatic cancer, NuCana is testing Acelarin with platinum-based chemo in biliary tract and ovarian cancers. It’s also developing it as a monotherapy for ovarian cancer. It has two earlier-stage prospects in its pipeline targeting colorectal cancer and other solid tumors as well as blood cancers. 

The Edinburgh, U.K.-based biotech has built its pipeline upon the same phosphoramidate chemistry approach that underpins Gilead Sciences' hepatitis C blockbuster Sovaldi. 

It has used the method to add a phosphate group protected by groupings of aryl, ester and amino acids to existing drugs. NuCana believes its retooled versions will be free from the membrane transport, activation and breakdown issues that can make cancer resistant to the products on which they’re based.

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