FDA Approves Atezolizumab for Alveolar Soft Part Sarcoma

Efficacy was evaluated in study ML39345 (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 ECOG performance status less than or equal to 2. Patients were excluded if they had 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 via IV and pediatric patients received 15 mg/kg (up to a maximum of 1,200 mg) via IV once every 21 days until they experienced disease progression or unacceptable toxicity.

The main efficacy outcome measures were overall response rate (ORR) and duration of response (DOR) determined by an independent review committee using RECIST v1.1. ORR was 24% (95% CI = 13, 39). Of the 12 patients who experienced an objective response, 67% had a DOR of six months or more and 42% had a DOR of 12 months or more.

Patients treated with atezolizumab had a median age of 31 years (range = 12–70); 47 adult patients (2% were at least aged 65 years) and two pediatric patients aged at least 12 years were enrolled. Of the patients treated, 51% were female and 55% were White, 29% were Black or African American, and 10% were Asian.

The most common adverse reactions reported in at least 15% of patients treated with atezolizumab were musculoskeletal pain (67%), 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 decreased (18% each), and allergic rhinitis and weight increased (16% each).

The recommended dosage of atezolizumab for adult patients is 840 mg every two weeks, 1,200 mg every three weeks, or 1,680 mg every four weeks until they experience 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 three weeks until patient experiences disease progression or unacceptable toxicity.

View the full prescribing information for atezolizumab (https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761034s047lbl.pdf).

The review used the Assessment Aid (https://www.fda.gov/about-fda/oncology-center-excellence/assessment-aid), a voluntary submission from the applicant to facilitate the FDA’s assessment. FDA approved the application three weeks ahead of the FDA goal date.

The application was granted priority review and breakthrough designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-serious-conditions-drugs-and-biologics). The application also was granted orphan drug designation.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 800-FDA-1088.

For assistance with single-patient investigational new drug applications, contact OCE’s Project Facilitate (https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov).