American Association for Cancer Research
ccr-23-0036_supplementary_figure_s3_suppfs3.docx (2.47 MB)

Supplementary Figure S3 from Devimistat in Combination with Gemcitabine and Cisplatin in Biliary Tract Cancer: Preclinical Evaluation and Phase Ib Multicenter Clinical Trial (BilT-04)

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posted on 2023-07-05, 08:23 authored by Arathi Mohan, Kent A. Griffith, Fulei Wuchu, David B. Zhen, Chandan Kumar-Sinha, Oxana Crysler, David Hsiehchen, Thomas Enzler, Dominique Dippman, Valerie Gunchick, Abhinav Achreja, Olamide Animasahun, Srinadh Choppara, Minal Nenwani, Arul M. Chinnaiyan, Deepak Nagrath, Mark M. Zalupski, Vaibhav Sahai

IC50 values for devimistat in biliary cancer cell lines


National Cancer Institute (NCI)

United States Department of Health and Human Services

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Cholangiocarcinoma Foundation



Devimistat (CPI-613) is a novel inhibitor of tumoral mitochondrial metabolism. We investigated the effect of devimistat in vitro and in a phase Ib clinical trial in patients with advanced biliary tract cancer (BTC). Cell viability assays of devimistat ± gemcitabine and cisplatin (GC) were performed and the effect of devimistat on mitochondrial respiration via oxygen consumption rate (OCR) was evaluated. A phase Ib/II trial was initiated in patients with untreated advanced BTC. In phase Ib, devimistat was infused over 2 hours in combination with GC on days 1 and 8 every 21 days with a primary objective to determine the recommended phase II dose (RP2D). Secondary objectives included safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). In vitro, devimistat with GC had a synergistic effect on two cell lines. Devimistat significantly decreased OCR at higher doses and in arms with divided dosing. In the phase Ib trial, 20 patients received a median of nine cycles (range, 3–19). One DLT was observed, and the RP2D of devimistat was determined to be 2,000 mg/m2 in combination with GC. Most common grade 3 toxicities included neutropenia (n = 11, 55%), anemia (n = 4, 20%), and infection (n = 3, 15%). There were no grade 4 toxicities. After a median follow-up of 15.6 months, ORR was 45% and median PFS was 10 months (95% confidence interval, 7.1–14.9). Median OS is not yet estimable. Devimistat in combination with GC is well tolerated and has an acceptable safety profile in patients with untreated advanced BTC.

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