On July 14, 2022, the U.S. Food and Drug Administration (FDA) approved crizotinib (Xalkori®) for adult and pediatric patients aged 1 and older with unresectable, recurrent, or refractory inflammatory anaplastic lymphoma kinase (ALK)-positive myofibroblastic tumors (IMT).
The drug’s safety and efficacy were evaluated in two multicenter, single-arm, open-label trials that included 14 pediatric patients from trial ADVL0912 (NCT00939770) and 7 adult patients from trial A8081013 (NCT01121588) with unresectable, recurrent, or refractory ALK-positive IMT.
The major efficacy outcome measure of both trials was objective response rate. Among the 14 pediatric patients, 12 (86%, 95% CI = 57, 98) experienced an objective response, assessed by an independent review committee. For the 7 adult patients, 5 had objective responses.
The most common adverse reactions (≥ 35%) in pediatric patients were vomiting, nausea, diarrhea, abdominal pain, rash, vision disorder, upper respiratory tract infection, cough, pyrexia, musculoskeletal pain, fatigue, edema, constipation, and headache. The most frequent adverse reactions (≥ 35%) in adult patients were vision disorders, nausea, and edema.
The recommended crizotinib dose in adult patients is 250 mg orally twice daily until patients experience disease progression or unacceptable toxicity. The recommended pediatric dose is 280 mg/m2 orally twice daily until patients experience disease progression or unacceptable toxicity.
View full prescribing information for crizotinib.
The review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
The application was granted priority review. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics. Crizotinib received 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 or by calling 800-FDA-1088.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.