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

Clin Cancer Res. 2023 Jul 5;29(13):2394-2400. doi: 10.1158/1078-0432.CCR-23-0036.


Purpose: 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).

Patients and methods: 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).

Results: 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.

Conclusions: Devimistat in combination with GC is well tolerated and has an acceptable safety profile in patients with untreated advanced BTC.

Publication types

  • Multicenter Study
  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Bile Duct Neoplasms* / drug therapy
  • Biliary Tract Neoplasms* / drug therapy
  • Biliary Tract Neoplasms* / etiology
  • Cisplatin
  • Deoxycytidine
  • Disease-Free Survival
  • Gemcitabine
  • Humans
  • Neutropenia* / chemically induced


  • Gemcitabine
  • devimistat
  • Cisplatin
  • Deoxycytidine