Devimistat Plus Hydroxychloroquine Trial for Soft Tissue Sarcoma Enrolls First Patient

A California-based study of devimistat plus hydroxychloroquine for soft tissue sarcoma has enrolled its first patient.

The first patient had been enrolled in a dose-finding study of devimistat (CPI-613) in combination with hydroxychloroquine (Plaquenil) for the treatment of relapsed or refractory clear cell sarcoma of the soft tissue, according to a press release by Rafael Pharmaceuticals, Inc.

Devimistat is designed to target the mitochondrial tricarboxylic acid cycle, which is an essential part of tumor cell proliferation and survival. The agent is meant to increase cellular stress while increasing the sensitivity of cancer cells to a diverse range of chemotherapeutic agents. This allows for a lower dose of generally toxic agents. Currently, the agent holds orphan drug designations in pancreatic cancer, acute myeloid leukemia, myelodysplastic syndrome, peripheral T-cell lymphoma, soft tissue sarcoma, Burkitt’s Lymphoma, and biliary tract cancer. 

“Clear cell sarcoma has the propensity to spread quickly within the body, and our current available medical therapies are not consistently beneficial to patients,” said Rashmi Chugh, MD, co-principal investigator from the University of Michigan, in a press release. “Finding effective treatments for the disease is critical, and we are hopeful that devimistat’s mechanism of action will be effective in clear cell sarcoma patients.”

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

During the single-arm study, patients will receive 2.5 mg/kg of hydroxychloroquine orally followed 2 hours later by 1000 mg/m2 of devimistat by infusion over 2 hours, followed by 2.5 mg/kg more of hydroxychloroquine 12 hours after the initial dose. This process will be completed on days 1 through 5 of every 28-day cycle.

“With the aggressive nature of clear cell sarcoma, finding a treatment for this rare cancer is a priority of ours,” said Sanjeev Luther, president and CEO of Rafael Pharmaceuticals, in a press release. “Enrolling a patient so soon after we opened the trial demonstrates the dire need for a treatment and the hope that devimistat brings to the rare cancer community. We opened two additional sites in order to increase access to the trial for patients in need.”

In order to participate, patients must be between 11 and 75 years of age. For patients 18 years of age and older, they must have a Karnofsky performance status of > 60 and an ECOG performance status of 0 to 2. Additionally, patients must have adequate organ, liver, neurological, and blood pressure function. Patients who have received chemotherapy within 7 days of initiation of study therapy, have a potentially curative anticancer therapy available to them, are pregnant or breastfeeding, known hypersensitivity to any of the study agents, have an uncontrolled infection, or immediate life-threatening complications are not eligible to participate.

The study is currently recruiting in California.

REFERENCES:
1.Rafael Pharmaceuticals announces first patient enrolled in APOLLO 613 phase 1/2 clinical trial of CPI-613® (Devimistat) in patients with relapsed clear cell sarcoma. News release. Rafael Pharmaceuticals. November 11, 2021. Accessed November 15, 2021. https://bit.ly/3wPtJ3V
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 November 15, 2021.