FDA Approves Crizotinib in Pediatric ALK+ Relapsed or Refractory Systemic ALCL

The FDA granted approval to the antineoplastic tyrosine kinase inhibitor, crizotinib, as treatment of pediatric patients 1 year of age and older and young adults with ALK alteration-positive relapsed or refractory systemic anaplastic large cell lymphoma.

The FDA granted approval to the antineoplastic tyrosine kinase inhibitor, crizotinib (Xalkori), as treatment of pediatric patients 1 year of age and older and young adults with ALK alteration-positive relapsed or refractory systemic anaplastic large cell lymphoma (ALCL), Pfizer announced in a press release. Crizotinib is the first biomarker-driven therapy approved for the treatment of this patient population.1

Crizotinib is not approved for the treatment of adult patients with ALK-positive ALCL, as safety efficacy has not been proven in this specific population. 

“We are proud to deliver the first biomarker-driven therapy for children and young adults with ALCL. Xalkori offers a meaningful new treatment option for young patients with relapsed or refractory ALK-positive ALCL,” said Chris Boshoff, MD, PhD, chief development officer, Oncology, Pfizer Global Product Development. “Xalkori transformed the treatment of ALK-positive non-small cell lung cancer as the first biomarker-driven therapy for that disease, and this approval is a notable milestone in our journey to continue to follow the science to address cancers with significant unmet need.”

Approval was granted based on data from phase 2 clinical trials including the phase 1/2 ADVL0912 study (NCT00939770), and the phase 1B A8081013 study (NCT01121588). In the ADVL0912 trial, crizotinib was administered to patients aged 16 years to 50 years with relapsed/refractory solid tumors or ALCL with ALK alterations or MET mutations or amplifications. The study completed in 2020 after first revealed the antitumor activity of crizotinib in the study population, most specifically for those with ALK-translocated ALCL as well as in patients with myofibroblastic tumors.

The study included 79 patients who were assessed for the coprimary end points of crizotinib’s maximum tolerated dose and recommended phase 2 dose, as well as the incidence of toxicities. Secondarily, the end points explored included the number of patients from each subgroup with a response to crizotinib, and the number of patients with minimal residual disease, and steady state peak concentration.2

Crizotinib led to an objective response rate (ORR) of 88% in the study. Of the patients who responded to therapy, 39% maintain their response for 6 months, and 22% maintained their response for 12 months.

Based on the results of the study, 280 mg/m2 twice daily was set at the MTD of crizotinib recommended for use in the second phase of the study. Crizotinib at the 280 mg/m2 was well-tolerated in patients.

Grade 4 adverse events (AEs) during cycle 1 were observed in the study. The events included neutropenia (n = 2), and liver enzyme elevation (n = 1). Two cases of grade 3 AEs were reported including 2 cases of lymphopenia and 8 of neutropenia. It was also noted that crizotinib had a mean steady state peak concentration of 630 ng/mL with a 4-hour (range, 1-6) time to reach the peak.

In terms of the secondary trial end points, objective responses were observed n 79 patients which included complete responses in 9 patients and partial responses in 5 patients. Notably, in the ALK-positive ALCL population, crizotinib achieved antitumor activity in all but one patient. In the neuroblastoma subgroup, the inflammatory myofibroblastic tumor group, and non–small cell lung cancer group, antitumor activity was also achieved.

Crizotinib also demonstrated antitumor activity in the A8081013 study of patients with ALK-rearranged hematologic tumors, including patients with ALCL.3

The overall study population included 44 patients and of those patients, 14 had ALK-positive ALCL and 1 patient had ALK-positive diffuse large B-cell lymphoma. Crizotinib led to an objective response rate of 60%, which included a CR in 9 patients and a PR in 4 patients. One patient also achieved stable disease which lasted for over 12 months. These results combined led to a clinical benefit rate of 67%.

AEs were observed in the entire study population, but most AEs were grade 1 or 2. Of the AEs observed, the most common were vomiting (47%), visual impairment (40%), asthenia (27%), cough (27%), and neutropenia (27%). Notably, grade 3 vomiting and neutropenia were observed.

Grade 4 events of abdominal pain, increased creatinine phosphokinase, lymphopenia, and multi-organ failure occurred in 4 patients. There was also 1 patient who experienced grade 5 central nervous system hemorrhage.


1. Pfizer’s XALKORI® (crizotinib) Approved by FDA for ALK-positive anaplastic large cell lymphoma in children and young adults. News release. Pfizer. 14. 2021. Accessed January 14, 2021.

2. Mossé YP, Lim MS, Voss SD, et al. Safety and activity of crizotinib for paediatric patients with refractory solid tumours or anaplastic large-cell lymphoma: a Children's Oncology Group phase 1 consortium study. Lancet Oncol. 2013;14(6):472-480. doi:10.1016/S1470-2045(13)70095-0

3. Gambacorti-Passerini C, Horibe K, Braiteh F, et al. Safety and clinical activity of crizotinib in patients with alk-rearranged hematologic malignancies. Blood. 2013;122(21);4342. doi:10.1182/blood.V122.21.4342.4342