January 14, 2021 – Crizotinib (Xalkori, Pfizer Inc.) for pediatric patients 1 year of age and older and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) that is ALK-positive. The safety and efficacy of crizotinib have not been established in older adults with relapsed or refractory, systemic ALK-positive ALCL.

March 11, 2016 - Crizotinib capsules (Xalkori, Pfizer, Inc.) for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are ROS1-positive.


January 14, 2021

https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/202570s030lbl.pdf

On January 14, 2021, the Food and Drug Administration approved crizotinib (Xalkori, Pfizer Inc.) for pediatric patients 1 year of age and older and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) that is ALK-positive. The safety and efficacy of crizotinib have not been established in older adults with relapsed or refractory, systemic ALK-positive ALCL.

Efficacy was evaluated in Study ADVL0912 (NCT00939770), a multicenter, single-arm, open-label trial in patients 1 to ≤21 years of age that included 26 patients with relapsed or refractory, systemic ALK-positive ALCL after at least one systemic treatment. Patients received crizotinib 280 mg/m(20 patients) or 165 mg/m2 (6 patients) orally twice daily until disease progression or unacceptable toxicity. Patients were permitted to discontinue crizotinib to undergo hematopoietic stem cell transplantation.

Efficacy was based on objective response rate (ORR) and duration of response as assessed by an independent review committee. The ORR in the 26 patients was 88% (95% CI: 71, 96), with a complete remission rate of 81%. Of the 23 patients who achieved a response, 39% maintained response for at least 6 months, and 22% maintained response for at least 12 months.

Ocular toxicity (Grade 1 or 2 visual disorders) occurred in 65% of patients with ALCL, gastrointestinal toxicity occurred in 92%, and serious adverse reactions occurred in 35%, most often from neutropenia and infection. The most common adverse reactions (≥35%), excluding laboratory abnormalities, were diarrhea, vomiting, nausea, vision disorder, headache, musculoskeletal pain, stomatitis, fatigue, decreased appetite, pyrexia, abdominal pain, cough, and pruritus. Grade 3-4 laboratory abnormalities (≥15%) were neutropenia, lymphopenia, and thrombocytopenia.

The recommended crizotinib dosage for systemic ALCL is 280 mg/m2 orally twice daily based on body surface area. Antiemetics are recommended prior to and during treatment with crizotinib in patients with ALCL. Due to the risk of visual loss, ophthalmologic evaluations are recommended at baseline and serially thereafter, coupled with monthly assessments of visual acuity and visual symptoms.

View full prescribing information for Xalkori.

This review used the  Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This application was granted priority review, breakthrough designation and orphan drug designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

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 1-800-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 This email address is being protected from spambots. You need JavaScript enabled to view it..

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March 11, 2016

http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/202570s016lbl.pdf

On March 11, 2016, the U. S. Food and Drug Administration approved crizotinib capsules (Xalkori®, Pfizer, Inc.) for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are ROS1-positive. Crizotinib was first approved in 2011 for the treatment of patients whose tumors are anaplastic lymphoma kinase (ALK)-positive.

The current approval was based on a multicenter, single-arm trial in patients with metastatic ROS1 rearrangement-positive NSCLC. All patients received crizotinib 250 mg orally twice daily. The efficacy outcome measures were objective response rate (ORR) according to RECIST v1.0 as evaluated by an independent radiology review (IRR) and as evaluated by the investigators. Duration of response (DoR) was an additional outcome measure.

The trial enrolled 50 patients with an age range of 25-77 years whose tumors were prospectively determined to be ROS1-positive by fluorescence in situ hybridization (FISH; 96%) or reverse transcription polymerase chain reaction (RT-PCR; 4%) clinical trial assays. The ORR by IRR was 66% (95% CI: 51%, 79%) with a median DoR of 18 months. The ORR according to investigators was 72% (95% CI: 58%, 84%).

The safety results of this trial were generally consistent with the safety profile of crizotinib evaluated in 1,669 patients with ALK-positive metastatic NSCLC. The most common adverse reactions of Xalkori are vision disorders, nausea, diarrhea, vomiting, edema, constipation, elevated transaminases, fatigue, decreased appetite, upper respiratory infection, dizziness, and neuropathy.

The recommended dose and schedule for crizotinib is 250 mg capsules taken by mouth twice daily.

This application was approved before the Prescription Drug User Fee Act (PDUFA) goal date of April 8, 2016. Crizotinib received Breakthrough Therapy Designation for the ROS1-positive development program and the application was granted Priority Review. A description of these expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics, available at: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf.

Full prescribing information is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/202570s016lbl.pdf

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 by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).