Devimistat (CPI-613^®) is a novel lipoate analog that inhibits the tricarboxcylic acid cycle at two key carbon entry points. Through its inhibition of pyruvate dehydrogenase and a-ketoglutarate dehydrogenase complexes, devimistat inhibits the entry of glucose and glutamine derived carbons, respectively. Pancreatic cancer is dependent on mitochondrial function for enhanced survival and aggressiveness. In a Phase I study of modified FOLFIRINOX, in combination with devimistat for metastatic pancreatic cancer patients, there was a 61% objective response rate including a 17% complete response rate. This report outlines the rationale and design of the AVENGER 500 study, a Phase III clinical trial of devimistat in combination with modified FOLFIRINOX compared with FOLFIRINOX alone for patients with previously untreated metastatic adenocarcinoma of the pancreas. Clinical trial registration: NCT03504423

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Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 15, No. 28

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History

Received 8 April 2019

Accepted 25 July 2019

Published online 12 September 2019

Published in print October 2019

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Acknowledgments

The authors would like to acknowledge insightful comments from the staff at Rafael Pharmaceuticals.

Financial & competing interests disclosures

AT Alistar has been a consultant for Rafael Pharmaceuticals, S Luther and TS Pardee are employees of Rafael Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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