FDA Approval Announcement
On July 14, 2022, the U.S. Food and Drug Administration (FDA) approved crizotinib (Xalkori, Pfizer Inc.) for adult and pediatric patients 1 year of age and older with unresectable, recurrent, or refractory anaplastic lymphoma kinase (ALK)-positive inflammatory myofibroblastic tumors (IMT).
Clinical Trials for Efficacy and Safety Evaluation
The safety and efficacy of crizotinib were evaluated in two multicenter, single-arm, open-label trials, with participants as follows:
Trial ADVL0912 (NCT00939770): 14 pediatric patients with unresectable, recurrent, or refractory ALK-positive IMT.
Trial A8081013 (NCT01121588): 7 adult patients with unresectable, recurrent, or refractory ALK-positive IMT.
Key Efficacy Results
The major efficacy outcome measure was objective response rate (ORR):
Pediatric patients (n=14): 86% ORR (12 out of 14 patients), with a 95% confidence interval (CI: 57, 98) (assessed by an independent review committee).
Adult patients (n=7): 5 patients achieved an objective response.
Common Adverse Reactions
Pediatric Patients (≥35%)
Vomiting, nausea, diarrhea, abdominal pain, rash, vision disorder, upper respiratory tract infection, cough, pyrexia, musculoskeletal pain, fatigue, edema, constipation, and headache.
Adult Patients (≥35%)
Vision disorders, nausea, and edema.
Recommended Dosage
Adult patients: 250 mg orally twice daily, continued until disease progression or unacceptable toxicity.
Pediatric patients: 280 mg/m² orally twice daily, continued until disease progression or unacceptable toxicity.
FDA Review and Designations
The review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
The application was granted Priority Review.
Crizotinib received Orphan Drug Designation.
A description of FDA expedited programs is available in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
