Nucana plc announces fda clearance to commence phase iii study of acelarin (nuc-1031) for the first-line treatment of patients with biliary tract cancer

Nucana plc announced that the us food and drug administration (fda) has cleared the investigational new drug application (ind) for its phase iii study (nutide:121) of the investigational drug acelarin in combination with cisplatin for patients with previously untreated locally advanced or metastatic biliary tract cancer. nutide:121 will be a global, multi-center, randomized phase iii study that will enroll up to 828 patients in approximately 120 sites across north america, europe, asia and australia. patients will be randomized 1:1 and treated with either a combination of acelarin (725 mg/m2) plus cisplatin (25 mg/m2) or the current standard of care regimen, gemcitabine (1,000 mg/m2) plus cisplatin (25 mg/m2). the primary objectives of nutide:121 are overall survival (os) and objective response rate (orr). three interim analyses, including two designed to support accelerated approval, are planned as part of the phase iii study protocol in addition to the final analysis. based on discussions with the fda and subject to any further regulatory guidance, the company believes that a statistically significant improvement in orr at either of the first two interim analyses, supported by positive trends in other endpoints, could potentially allow for an accelerated approval of a new drug application (nda) for acelarin. accelerated approval requires a confirmatory clinical study to verify the drug’s clinical benefit. if accelerated approval were to occur, nutide:121 would continue and the company anticipates that data from subsequent analyses could provide the confirmatory data to support full (regular) approval. nutide:121 statistical analysis plan (sap): three interim efficacy analyses, including two designed to support accelerated approval of acelarin in the united states, are currently planned in addition to the final analysis. the first interim analysis will evaluate the orr primary endpoint and will be performed 22 weeks after 418 patients with measurable disease at baseline have been randomized. a statistically significant difference in orr at this analysis would require the acelarin plus cisplatin arm to have an orr at least 14% higher than that of the gemcitabine plus cisplatin arm. the second interim analysis will evaluate the orr and os primary endpoints. it will be performed 28 weeks after 644 patients with measurable disease at baseline have been randomized. a statistically significant difference in orr at this analysis would require the acelarin plus cisplatin arm to have an orr approximately 9% higher than that of the gemcitabine plus cisplatin arm. if a statistically significant difference in orr is detected, os will also be analyzed at this analysis and a difference in median os of approximately 3.4 months in favor of acelarin plus cisplatin would be deemed a statistically significant improvement in os. the third interim analysis will evaluate the os primary endpoint and will take place after 541 events have been observed. a statistically significant difference for os in favor of acelarin plus cisplatin would be achieved with an improvement in median os of approximately 2.6 months. the final analysis will evaluate the os primary endpoint. it will take place after 637 events have been observed. a statistically significant difference for os in favor of acelarin plus cisplatin would be achieved with an improvement in median os of approximately 2.2 months.
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