On December 9, the U.S. Food and Drug Administration (FDA) approved atezolizumab (Tecentriq) for the treatment of adult and pediatric patients aged 2 years and older with unresectable or metastatic alveolar soft-part sarcoma (ASPS).
Study ML39345
Efficacy was evaluated in Study ML39345 (ClinicalTrials.gov identifier NCT03141684), an open-label, single-arm study in 49 adult and pediatric patients with unresectable or metastatic ASPS. Eligible patients were required to have histologically or cytologically confirmed ASPS incurable by surgery and an Eastern Cooperative Oncology Group performance status of up to 2. Patients were excluded for primary central nervous system (CNS) malignancy or symptomatic CNS metastases; clinically significant liver disease; or a history of idiopathic pulmonary fibrosis, pneumonitis, organizing pneumonia, or active pneumonitis on imaging. Adult patients received 1,200 mg of atezolizumab intravenously and pediatric patients received 15 mg/kg (up to a maximum of 1,200 mg) intravenously once every 21 days until disease progression or unacceptable toxicity.
The median patient age was 31 years (range = 12–70 years); 47 adult patients (2% were ≥ 65 years of age) and 2 pediatric patients ≥ 12 years of age were enrolled; 51% were female; and 55% were White, 29% were Black, and 10% were Asian.
The main efficacy outcome measures were overall response rate and duration of response, determined by an independent review committee using Response Evaluation Criteria in Solid Tumors version 1.1. Overall response rate was 24% (95% confidence interval = 13%–39%). Of the 12 patients who experienced an objective response, 67% had a duration of response of 6 months or more, and 42% had a duration of response of 12 months or more.
The most common adverse reactions (≥ 15%) were musculoskeletal pain (in 67% of patients); fatigue (55%); rash (47%); cough (45%); nausea, headache, and hypertension (43% each); vomiting (37%); constipation and dyspnea (33% each); dizziness and hemorrhage (29% each); insomnia and diarrhea (27% each); pyrexia, anxiety, abdominal pain, and hypothyroidism (25% each); decreased appetite and arrhythmia (22% each); influenza-like illness and weight loss (18% each); and allergic rhinitis and weight gain (16% each).
The recommended atezolizumab dosage for adult patients is 840 mg every 2 weeks, 1,200 mg every 3 weeks, or 1,680 mg every 4 weeks until disease progression or unacceptable toxicity. The recommended dosage for pediatric patients aged 2 years and older is 15 mg/kg (up to a maximum of 1,200 mg) every 3 weeks 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 FDA approved this application 3 weeks ahead of the FDA goal date.
This application was granted Priority Review, Breakthrough Therapy designation, and Orphan Drug designation.
