Devimistat Now Being Explored for the Treatment of Clear Cell Sarcomas in the United States

Patients with relapsed or refractory clear cell sarcoma are being recruited for a phase 1/2 study of devimistat (CPI-613) in combination with hydroxychloroquine at the City of Hope Comprehensive Cancer Center, according to a press release issued by the developer, Rafael Pharmaceuticals, Inc.¹

Devimistat has been shown to synergize with low-dose chemotherapy to improve the therapeutic benefit in patients. The agent increasing cellular stress by targeting mitochondrial tricarboxylic acid, a process by which tumor cells can multiply. The agent has been granted an orphan drug designation by the FDA for the treatment of soft tissue sarcoma.

“We are optimistic that this trial will provide a potential path forward for individuals suffering from clear cell sarcoma, one of the rarest diseases in the world,” said Mark Agulnik MD, Sarcoma Section chief in the Department of Medical Oncology & Therapeutics Research, and clinical professor in the Department of Medical Oncology & Therapeutics Research at City of Hope Comprehensive Cancer Center and the principal investigator of APOLLO613, in the press release.

APOLLO613 (NCT04593758) has an open-label design and aims to evaluate the coprimary end points of maximum-tolerated dose of devimistat and safety in the phase 1 portion of the study in addition to the phase primary end point of overall response rate. The secondary end points of the study are duration of response, progression-free survival, and overall survival.²

In an estimated 47 patients, treatment will begin with hydroxychloroquine 2.5 mg/kg followed 2 hours later by devimistat will be administered at 1,000 mg/m² by central intravenous infusion over 2 hours. The devimistat infusion will be following by another dose of hydroxychloroquine 12 hours after the initial dose. This treatment scheme will be conducted on days 1 through 5 of every 28-day cycle.

Per the study’s inclusion criteria, patients are required to be between the ages of 11 and 75 years old. All patients must have a Karnofsky performance status of > 60 for patients under the age of 18 and adults must have an ECOG performance status of 0-2. Finally, patients must also have adequate organ, bone marrow, liver, and neurologic function alone with adequate blood pressure control.

The study excludes individuals who have received chemotherapy within 7 days of treatment imitation, patients who have available curative therapies, known hypersensitivity to any of the therapies use in APOLLO613, and those with other conditions that may interfere with study treatment.

Rafael Pharmaceuticals, Inc explained, in the press release that more clinical trial locations are soon to come.¹

“This aggressive sarcoma afflicts patients of all ages, especially children and young adults. Currently, available standard therapies are limited in their benefit to patients,” said Rashmi Chugh, M.D., medical oncologist from the University of Michigan. Matteo Trucco MD, pediatric oncologist from the Cleveland Clinic added, in the press release “This trial is pivotal as we work towards additional treatment options for patients and families affected by this aggressive disease.” Chugh and Trucco are both co-principal investigators on this multicenter study.

Outside of the sarcoma landscape, devimistat is FDA approved to treat acute myeloid leukemia (AML) and had orphan drug designation for pancreatic cancer, AML, myelodysplastic syndrome, peripheral T-cell lymphoma, Burkitt’s lymphoma, and biliary tract cancer. The drug also has the attention of the European Medicines Agency with orphan drug designations granted for the treatment of pancreatic cancer and AML.

_References:

_{1. Rafael Pharmaceuticals Announces APOLLO613 phase i/ii clinical trial of CPI-613® (devimistat) in enrollment at combination with hydroxychloroquine in patients with relapsed clear cell sarcoma begins City of Hope in Duarte, Calif. News release. Rafael Pharmaceuticals, Inc. September 27, 2021. Accessed September 27, 2021. https://bit.ly/39GZpxv}

_{2. 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 September 27, 2021.}