Study of Devimistat for Clear Cell Sarcoma Moves on to Treat Second Relapsed Clear Cell Sarcoma Cohort

No dose-limiting toxicities have been observed at the completion of the dose-escalation of devimistat (CPI-613) in patients with relapse clear cell sarcoma treated in the phase 1/2 Apollo 613 study, according to a press release by Rafael Pharmaceuticals, Inc.

Devimistat targets enzymes that are involved in cancer cell energy metabolism located in the mitochondria of cancer cells. It goes after the mitochondrial tricarboxylic acid cycle, which is essential to tumor cell survival and reproduction. Current, devimistat has an orphan drug designation in pancreatic cancer, acute myeloid leukemia, myelodysplastic syndrome, peripheral T-cell lymphoma, soft tissue sarcoma, Burkitt’s lymphoma, and biliary tract cancer.

“Enrolling patients into our second cohort of dose-escalation so soon after establishing safety in the first cohort demonstrates the dire need and demand for effective treatments for rare sarcomas,” said Rashmi Chugh, MD, co-principal investigator on the trial and clinical professor at the University of Michigan Health in the press release. “We are hopeful that devimistat will produce favorable outcomes for those suffering from relapsed clear cell sarcoma.”

The phase 1/2 Apollo 613 study (NCT04593758) has an estimated enrollment of 47 participants and an estimated study completion date of November 2024. The primary end points include maximum tolerated dose, toxicity, and overall response rate. Secondary end points include duration of response, progression-free survival, and overall survival.

During the study, patients received a combination of devimistat and hydroxychloroquine. Hydroxychloroquine was administered at a dose of 2.5 mg/kg followed by 1000 mg/m2 of CPI-613 2 hours later. Twelve hours after the initial dose, 2.5 mg/kg of hydroxychloroquine was administered daily on days 1 through 5 of each 28-day cycle.

In order to participate in the study, patients must be between 11 and 75 years old, have an ECOG performance status of 2 or less, and have adequate organ function. Patients who have received any other chemotherapy within 7 days of initiation of study therapy or immunotherapy based within 28 days of study initiation, can revied potentially curative anticancer therapy, or are pregnant or breastfeeding are not eligible to participate.

“The success of our first cohort of dose escalation increases our optimism that devimistat may help address the gaps for efficacious treatment methods for relapsed clear cell sarcoma,” said Sanjeev Luther, president and chief executive officer of Rafael, in the press release. “There is a significant unmet need in treatments for clear cell sarcoma and other rare cancers, and as such, patients and physicians in the rare disease community are incredibly hopeful of devimistat’s capabilities.”

_REFERENFES:

_{Rafael Pharmaceuticals announces successful completion of dose escalation with no dose-limiting toxicity (DLT) in first cohort of APOLLO 613 phase 1/2 clinical trial of CPI-613® (devimistat) in patients with relapsed clear cell sarcoma. News release. Rafael Pharmaceuticals. January 6, 2022. Accessed January 7, 2022.}

_{To evaluate maximally tolerated dose (MTD), safety and efficacy of CPI-613® (Devimistat) plus hydroxychloroquine in patients with relapsed or refractory clear cell sarcoma of soft tissue. ClinicalTrials.gov. Accessed January 7, 2022.}