FDA approval of crizotinib for the treatment of pediatric patients and young adults with ALK-positive R/R ALCL

On January 14, 2021, it was announced that the U.S. Food and Drug Administration (FDA) granted the approval of crizotinib for the treatment of pediatric patients and young adults (1 to ≤ 21 years) with anaplastic lymphoma kinase (ALK)-positive, relapsed/refractory (R/R), systemic anaplastic large cell lymphoma (ALCL). The approval was based on the results of the phase I/II ADVL0912 study (NCT00939770).¹

Crizotinib¹

• An oral small molecule tyrosine kinase inhibitor.
• Approved by the FDA, European Medicines Agency (EMA), and various other regulatory agencies, for the treatment of patients with ALK- or c-ros oncogene 1 (ROS1)-positive metastatic non-small cell lung cancer.
• Previously granted FDA priority review for ALK-positive, R/R systemic ALCL.

ADVL0912 study^1,2

• A single arm, open-label, multicenter, study of 121 patients (1 to ≤ 21 years) with R/R solid tumors and ALCL, of which 26 were ALK-positive.
• Primary outcome measures: maximum tolerated dose, recommended phase II dose, toxicities, pharmacokinetics, and pharmacodynamics.
• Secondary outcome measures: overall response, and number of participants with minimum residual disease.

Results¹

• The overall response rate for patients who were ALK-positive was 88%.
  • Responses were maintained for ≥ 6 months in 39% of patients, and ≥ 12 months in 22% of patients.
• Toxicities were similar to those for patients with non-small cell lung cancer.
  • Excluding laboratory abnormalities, the most common adverse events (≥ 35%), were diarrhea, vomiting, nausea, vision disorder, headache, musculoskeletal pain, stomatitis, fatigue, decreased appetite, pyrexia, abdominal pain, cough, and pruritis.
  • The most common Grade 4 hematological adverse events included neutropenia (62%), lymphopenia (35%), and thrombocytopenia (19%).

The EMA has also agreed to a pediatric investigational plan for crizotinib in ALK-positive, R/R systemic ALCL, providing hope for a potential European approval.¹