Early Study of Devimistat/Gemcitabine in Biliary Cancer Concludes

A study of devimistat in combination with gemcitabine and cisplatin indicated for patients with locally advanced unresectable or metastatic biliary tract cancer has been successfully completed.

A phase 1b clinical trial testing devimistat (CPI-613) in combination with gemcitabine and cisplatin indicated for patients with locally advanced unresectable or metastatic biliary tract cancer has been successfully completed.1

This multicenter trial (NCT04203160) enrolled 20 patients in its phase 1b segment and found the gemcitabine, cisplatin, devimistat combination to be well tolerated. The overall response rate was 45%, and the median progression-free survival (PFS) was 14.9 months. Seven patients are still in treatment. The median overall survival (OS) is not estimable after a median follow-up of 11.5 months.

The randomized phase 2 portion of the trial is now open and collecting patients from 10 cancer centers across the US, with a target enrollment of 78 patients.

“We are very pleased with the results of the trial, as we advance to phase 2,” said Sanjeev Luther, president, and CEO of Cornerstone Pharmaceuticals. “Advanced biliary tract cancer is a rare and aggressive form of cancer with a 5-year survival rate of less than 5%. The continuation of the trial aligns with our mission to provide hope to patients and loved ones affected by biliary tract cancer and other rare cancers.”

“With strong and continued trial enrollment rates, the research community remains engaged in identifying the capabilities devimistat has in biliary cancer,” said Vaibhav Sahai, MD, MBBS, MS, principal investigator of the trial and medical oncologist at the University of Michigan Rogel Cancer Center in Ann Arbor, Michigan. “Devimistat is a potentially life-saving therapy, and we remain optimistic in its promise as the study continues to yield positive results, giving us great hope for the future of biliary cancer care.”

Devimistat targets enzymes involved in cancer cell energy metabolism, located in the mitochondria. This treatment is aimed to target the mitochondrial tricarboxylic acid cycle in cancer cells. The FDA gave devimistat an orphan drug designation for the treatment of pancreatic cancer, acute myeloid leukemia, myelodysplastic syndrome, peripheral T-cell lymphoma, soft tissue sarcoma, Burkitt’s lymphoma, and biliary tract cancer.1

The phase 1 primary outcome of the study is the incidence of dose-limiting toxicity which will determine the recommended phase 2 dosage. The secondary end points are PFS, OS, and incidence of toxicities.2

Eligible patients must have a pathologically or cytologically confirmed carcinoma of the biliary tract that is not eligible for curative resection, transplantation, or ablative therapies. Patients with tumors of mixed cholangiocarcinoma/hepatocellular carcinoma histology are excluded. Patients must also have radiographically measurable disease in at least 1 site not previously treated with radiation or liver-directed therapy, be of at least 18 years of age, and have an ECOG performance score of 0 or 1.

Patients are excluded from the study if they have prior history of brain metastasis or organ transplant, underwent a major surgical procedure less than 4 weeks before enrollment, active second malignancy other than in situ cancer or localized prostate cancer, active heart disease including symptomatic heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia or interstitial lung disease, or known hypersensitivity to cisplatin, gemcitabine, or CPI-613, or its inactive components.


1. Cornerstone pharmaceuticals announces successful completion of phase 1b clinical trial for CPI-613® (devimistat) in combination with gemcitabine and cisplatin in patients with biliary tract cancer. Press release. Yahoo Finance; August 3, 2022. Accessed August 8, 2022. https://yhoo.it/3JEEr3F

2. Gemcitabine and cisplatin with or without CPI-613 as first line therapy for patients with advanced unresectable biliary tract cancer (BilT-04). ClinicalTrials.gov. Updated May 25, 2022. Accessed August 8, 2022. https://bit.ly/3bE3Spj