FDA clears Pfizer's Xalkori for ALK-positive ALCL in children, young adults

Pfizer said Thursday that the FDA has expanded the label for Xalkori (crizotinib) to include treatment of paediatric patients one year and older as well as young adults with relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) that is ALK-positive. According to Pfizer, this makes Xalkori the first biomarker-driven therapy for relapsed or refractory ALCL in young people.

Chris Boshoff, chief development officer for oncology at Pfizer's global product development unit, noted that Xalkori has "transformed the treatment of ALK-positive non-small-cell lung cancer (NSCLC) 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." The tyrosine kinase inhibitor is already approved in the US for patients with metastatic NSCLC whose tumours are ALK-positive or ROS1-positive as detected by an FDA-approved test.

Response rate of 88%

The company's latest filing was supported by data from a Phase I/II trial, dubbed Study ADVL0912, involving 121 patients between the ages of one and 21 years with relapsed or refractory solid tumours or ALCL. Among these, there were 26 who had systemic ALK-positive ALCL after at least one systemic treatment. Pfizer said that in this group, Xalkori was associated with an objective response rate of 88%. Further, among the 23 patients who achieved a response, 39% maintained their response for at least six months, while 22% maintained their response for at least a year.

In terms of safety, Pfizer said treatment with Xalkori in Study ADVL0912 was "generally consistent" with what has been seen in patients with ALK-positive and ROS1-positive metastatic NSCLC. It noted that visual disorders occurred in 46% of the 121 participants in Study ADVL0912 treated with the drug, including 65% of the 26 ALCL patients. Meanwhile, grade 4 laboratory abnormalities included neutropenia, lymphopenia and thrombocytopenia, which occurred at rates of 62%, 35% and 19%, respectively. Pfizer noted that the safety and efficacy of Xalkori have not been established in older adults with relapsed or refractory, systemic ALK-positive ALCL.

The drug was granted a breakthrough therapy designation for the ALK-positive ALCL indication in 2018. Meanwhile, the European Medicines Agency has agreed to a Paediatric Investigational Plan (PIP) for Xalkori that Pfizer says provides a path for a potential regulatory submission in paediatric patients with relapsed or refractory ALK-positive ALCL in the EU.

In November, the company reported Phase III findings from the CROWN trial showing that its third-generation ALK inhibitor Lorbrena (lorlatinib) cut the risk of disease progression or death by a significant 72% compared to Xalkori in patients with previously untreated ALK-positive advanced NSCLC.

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