Pfizer gets USFDA nod for XALKORI (crizotinib) to treat ALK-positive ALCL in children and young adults

Pfizer announced that the US Food and Drug Administration (FDA) approved the supplemental New Drug Application (sNDA) for XALKORI (crizotinib) for the treatment of paediatric patients one year of age and older and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) that is anaplastic lymphoma kinase (ALK)-positive. The safety and efficacy of XALKORI have not been established in older adults with relapsed or refractory, systemic ALK-positive ALCL. ALCL is a rare form of non-Hodgkin lymphoma (NHL) and accounts for approximately 30 per cent of cases of NHL in young people. Approximately 90 per cent of ALCL cases in young people are ALK-positive.

Although the majority of people with ALK-positive ALCL respond well to chemotherapy and experience long-term remission, a number of patients will unfortunately relapse or require alternative treatment approaches.

Chris Boshoff, Chief Development Officer, Oncology, Pfizer Global Product Development said, “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.”

Yael Mossé, Associate Professor of Pediatrics at the University of Pennsylvania/ Children’s Hospital of Philadelphia and Principal Investigator for the pivotal study run through the Children’s Oncology Group said, “ALK fusions play an important role in the pathology of ALCL, and it’s exciting that XALKORI is able to leverage this dependence to provide a treatment option for young people faced with ALCL disease progression.”

The FDA approval is based on results from Study ADVL0912 (NCT00939770), a multicenter, single arm, open-label study in 121 patients between the ages of 1 and 21 that included 26 patients with relapsed or refractory, systemic ALK-positive ALCL after at least one systemic treatment. Treatment with XALKORI resulted in an objective response rate of 88%. Among the 23 patients who achieved a response, 39 per cent maintained their response for at least six months and 22 per cent maintained their response for at least 12 months.

The safety profile of XALKORI in ALK-positive ALCL in children and young adults is generally consistent with that observed in patients with ALK-positive and ROS1-positive metastatic NSCLC. 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 pruritis. The most common Grade 3 or 4 laboratory abnormalities (≥15%) included neutropenia, lymphopenia and thrombocytopenia. Grade 4 laboratory abnormalities (≥15%) included neutropenia (62%), lymphopenia (35%) and thrombocytopenia (19%). In Study ADVL0912, visual disorders occurred in 46% of 121 patients treated with XALKORI, including 65% of the 26 patients diagnosed with ALCL.

XALKORI received Breakthrough Therapy designation (BTD) from the FDA for the ALK-positive ALCL indication in May 2018. The European Medicines Agency (EMA) has agreed to a Paediatric Investigational Plan (PIP) for XALKORI including the treatment of paediatric patients with relapsed or refractory systemic ALK-positive ALCL. This agreement provides a path for a potential regulatory submission for XALKORI in paediatric patients with relapsed or refractory ALK-positive ALCL in the European Union.