On November 22, 2021, the U.S. Food and Drug Administration (FDA) approved sirolimus protein-bound particles for injectable suspension (Fyarro™) for adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa).
Efficacy was evaluated in a multicenter, single-arm clinical trial (AMPECT; NCT02494570) in 31 patients with locally advanced unresectable or metastatic malignant PEComa. Patients received sirolimus protein-bound particles at 100 mg/m2 on days 1 and 8 of each 21-day cycle until they experienced disease progression or unacceptable toxicity.
The main efficacy outcome measures were overall response rate (ORR) and duration of response (DOR), as assessed by a blinded independent central review using response evaluation criteria in solid tumors 1.1. ORR was 39% (95% CI = 22%, 58%), including two patients with complete responses. Median DOR was not reached (95% CI = 6.5 months, not estimable). Among responders, 67% had a response lasting greater than 12 months and 58% had a response lasting greater than 24 months.
The most common adverse reactions reported in 30% or more of patients were stomatitis, fatigue, rash, infection, nausea, edema, diarrhea, musculoskeletal pain, decreased weight, decreased appetite, cough, vomiting, and dysgeusia. The most common grade 3–4 laboratory abnormalities reported in 6% or more of patients were decreased lymphocytes, potassium, phosphate, and hemoglobin and increased lipase and glucose.
The recommended dosage is 100 mg/m2 administered via IV infusion over 30 minutes on days 1 and 8 of each 21-day cycle until patients experience disease progression or unacceptable toxicity.
The review used the Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment.
FDA granted the application priority review, fast track designation, breakthrough therapy designation, and orphan drug designation. A description of FDA expedited programs is in the Guidance for IndustryꟷExpedited Programs for Serious ConditionsꟷDrugs and Biologics.
Healthcare professionals should report all serious adverse events they suspect are associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.