On November 22, the U.S. Food and Drug Administration (FDA) approved sirolimus protein-bound particles for injectable suspension (albumin-bound; Fyarro) for adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa).
Efficacy was evaluated in AMPECT (ClinicalTrials.gov identifier NCT02494570), a multicenter, single-arm clinical trial 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 disease progression or unacceptable toxicity. The main efficacy outcome measures were overall response rate and duration of response as assessed by blinded independent central review, using Response Evaluation Criteria in Solid Tumors version 1.1.
The overall response rate was 39% (95% confidence interval [CI] = 22%–58%), including two patients with complete responses. Median duration of response was not reached (95% CI = 6.5 months–not estimable). Among responders, 67% had a response lasting longer than 12 months and 58% had a response lasting longer than 24 months.
The most commonly reported (≥ 30%) adverse reactions were stomatitis, fatigue, rash, infection, nausea, edema, diarrhea, musculoskeletal pain, decreased weight, decreased appetite, cough, vomiting, and dysgeusia. The most common (≥ 6%) grade 3 or 4 laboratory abnormalities were decreased lymphocytes, increased glucose, decreased potassium, decreased phosphate, decreased hemoglobin, and increased lipase.
The recommended dosage of sirolimus protein-bound particles is 100 mg/m2 administered as an intravenous infusion over 30 minutes on days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxicity.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment; the application was granted Priority Review, Fast Track designation, Breakthrough Therapy designation, and Orphan Drug designation.