FDA Approves Crizotinib for ALK-Positive Inflammatory Myofibroblastic Tumors

The FDA has granted approval to crizotinib (Xalkori) as treatment for adult and pediatric patients aged 1 year and older with unresectable, recurrent, or refractory inflammatory ALK-positive myofibroblastic tumors (IMT).¹

Approval of the agent was based on the safety and efficacy findings of 2 multicenter, single-arm, open-label trials, ADVL0912 (NCT00939770) and A8081013 (NCT01121588), which evaluated crizotinib in patients had unresectable, recurrent, or refractory ALK-positive IMT. For both trials, the major efficacy outcome was objective response rate (ORR).

Within the ADVL0912, which enrolled 14 pediatric patients, the ORR achieved with crizotinib was 86% (95% CI, 57%-98%) per independent review committee assessment. In the A8081013 trial, 7 adult patients were enrolled with 5 having achieved objective responses with crizotinib.

In regard to safety, the most common toxicities experienced by pediatric patients who were administered crizotinib included vomiting, nausea, diarrhea, abdominal pain, rash, vision disorder, upper respiratory tract infection, cough, pyrexia, musculoskeletal pain, fatigue, edema, constipation, and headache. The most common adverse events experienced by adult patients who received the agent were vision disorders, nausea, and edema.

The phase 1/2 ADVL0912 study examined the side effects, aimed to determine the best dose of crizotinib, and evaluated how well the agent works in treating young patients, aged 1-21. The 14 patients enrolled had metastatic or inoperable ALK-positive IMT and received crizotinib orally twice daily.²

In the phase 1 trial, A8081013, investigators evaluated the safety and efficacy of crizotinib in patients with tumors, not including non-small cell lung cancer, that were positive for ALK. Enrolled patients were those aged 15 years and older and administered crizotinib tablets at a dose of 250 mg orally on a continuous dosing schedule.³

References

1. FDA approves crizotinib for ALK-positive inflammatory myofibroblastic tumor. News release. FDA. July 14, 2022. Accessed July 14, 2022. https://bit.ly/3uK0yze

2. Crizotinib in Treating Younger Patients With Relapsed or Refractory Solid Tumors or Anaplastic Large Cell Lymphoma. ClinicalTrials.gov. Updated June 9, 2022. Accessed July 14, 2022. https://clinicaltrials.gov/ct2/show/NCT00939770

3. An Investigational Drug, Crizotinib (PF-02341066), Is Being Studied In Tumors, Except Non-Small Cell Lung Cancer, That Are Positive For Anaplastic Lymphoma Kinase (ALK). ClinicalTrials.gov. Updated October 7, 2021. Accessed July 14, 2022. https://clinicaltrials.gov/ct2/show/NCT01121588