FDA Grants Devimistat Orphan Drug Status for Soft Tissue Sarcoma


The clinical trial planned to evaluate the targeted agent will focus on patients with relapsed/refractory clear cell sarcoma.

The FDA has granted an orphan drug designation to devimistat (CPI-613) for the treatment of patients with soft tissue sarcoma, according to the developer Rafael Pharmaceuticals.1

The clinical trial planned to evaluate the targeted agent will focus on patients with relapsed/refractory clear cell sarcoma.

“There is a significant unmet need in treatment for soft tissue sarcoma,” said Sanjeev Luther, president and CEO of Rafael Pharmaceuticals. “When a disease is rare, it often does not receive the attention and focus necessary to develop effective treatments for it. We want to be a voice for those diagnosed with hard-to-treat cancers so that they know that they are not forgotten. We are focusing our attention on developing treatments for these cancers. In fact, Rafael is one of the only companies working on a treatment for clear cell sarcoma.”

Devimistat is a first-in-class compound that targets enzymes involved in cancer cell energy metabolism and are located in cancer cell mitochondria of cancer cells. The agent targets the mitochondrial tricarboxylic acid cycle, and then increases the sensitivity of cancer cells to chemotherapy; the mechanism could also allow for potential combination regimens.

In November 2020, the FDA granted a fast-track designation to devimistat for the treatment of patients with pancreatic cancer.

The pivotal phase 3 AVENGER 500 trial (NCT03504423), which is evaluating the efficacy and safety of devimistat for patients with metastatic pancreatic cancer, achieved its target enrollment of 500 patients in September 2020.

In the international, open-label study, investigators are examining devimistat plus modified FOLFIRINOX versus FOLFIRINOX alone in treatment-naïve adults, aged 18 to 75 years old, with stage IV metastatic pancreatic cancer in a 1:1 randomization. In the experimental arm, patients are administered 500 mg/m2 of devimistat on days 1 and 3 of a 14-day cycle, followed by standard dose and schedule of 5-fluorouracil, but reduced doses of oxaliplatin (65 mg/m2) and irinotecan (140 mg/m2). In the control arm, patients will receive standard-dose FOLFIRINOX.

Investigators will conduct an interim analysis after 167 patients are evaluable for response.

The coprimary end points of the trial are overall response rate (ORR) and progression-free survival (PFS). An independent, blinded, central review will assess best response within the first 12 cycles to determine ORR. Secondary outcome measures include overall survival (OS), duration of response, and safety.

Previously, the single-center, open-label, dose-escalation CCCWFU 57112 trial (NCT01835041) evaluated the safety and efficacy of devimistat plus modified FOLFIRINOX in CCCWFU 57112 (NCT01835041), in which the maximum-tolerated dose (MTD) of devimistat was 500 mg/m2.2

Among the 18 patients who received the MTD, the ORR was 61%, with a median OS of 19.9 months and a median 9.9-month PFS.

Rafael Pharmaceuticals also recently announced that they had crossed enrollment of 100 patients in a phase 3 trial that is evaluating devimistat in patients with relapsed/refractory acute myeloid leukemia.


1. FDA Grants Rafael Pharmaceuticals Orphan Drug Designation for CPI-613® (devimistat) for Treatment of Soft Tissue Sarcoma. News release. Rafael Pharmaceuticals. October 29, 2020. Accessed November 23, 2020. https://bit.ly/35WsDqY

2. Alistar A, Morris BB, Desnoyer R, et al. Safety and tolerability of the first-in-class agent CPI-613 in combination with modified FOLFIRINOX in patients with metastatic pancreatic cancer: a single-centre, open-label, dose-escalation, phase 1 trial. Lancet Oncol. 2017;18(6):770-778. doi:10.1016/S1470-2045(17)30314-5

This article was originally published on OncLive as, "Devimistat Granted Orphan Drug Status for Soft Tissue Sarcoma."

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