On 14 July 2022, the US Food and Drug Administration (FDA) approved crizotinib (Xalkori, Pfizer Inc.) for adult and paediatric patients 1 year of age and older with unresectable, recurrent, or refractory inflammatory anaplastic lymphoma kinase (ALK)-positive myofibroblastic tumours (IMT).

The safety and efficacy of crizotinib were evaluated in two multicentre, single-arm, open-label studies that included 14 paediatric patients from ADVL0912 study (NCT00939770) and 7 adult patients from A8081013 study (NCT01121588) with unresectable, recurrent, or refractory ALK-positive IMT.

The major efficacy outcome measure of these studies was objective response rate. For the 14 paediatric patients, a total of 12 of the 14 patients (86%, 95% confidence interval 57, 98) experienced an objective response, assessed by an independent review committee. For the 7 adult patients, 5 patients had objective responses.

The most common adverse reactions (≥ 35%) in paediatric patients were vomiting, nausea, diarrhoea, abdominal pain, rash, vision disorders, upper respiratory tract infection, cough, pyrexia, musculoskeletal pain, fatigue, oedema, constipation, and headache. The most frequent adverse reactions (≥ 35%) in adult patients were vision disorders, nausea, and oedema.

The recommended crizotinib dose in adult patients is 250 mg orally twice daily until disease progression or unacceptable toxicity. The recommended paediatric dose is 280 mg/m2 orally twice daily until disease progression or unacceptable toxicity.

Full prescribing information for Xalkori is available here.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

This application was granted priority review. 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.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact FDA’s Oncology Center of Excellence Project Facilitate.