The US Food and Drug Administration (FDA) has approved a new indication for Pfizer’s Lorbrena in the first-line treatment of metastatic anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).
The expanded approval is based on the phase 3 CROWN trial, which demonstrated that Lorbrena (lorlatinib) reduced the risk of disease progression or death by 72% in metastatic ALK-positive NSCLC patients compared to Xalkori (crizotinib).
In addition, Lorbrena also showed benefit in patients with central nervous system involvement. There were 17 patients in the Lorbrena arm and 13 in the Xalkori arm with measurable brain metastases based on baseline imaging.
An exploratory analysis showed that among these patients, the intracranial objective response rate (IC-ORR) was 82% in the Lorbrena arm compared to 23% in the Xalkori arm.
In addition, the intracranial duration of response was 12 months or longer in 79% of Lorbrena-treated patients compared to 0% in the Xalkori arm.
The FDA granted Lorbrena an accelerated approval in 2018 for the second- or third-line treatment of patients with ALK-positive metastatic NSCLC, whose disease has progressed on Xalkori and at least one other ALK inhibitor.
Based on the CROWN data, the FDA has now converted the accelerated approval to a full approval.
“Lorbrena has been a transformative medicine for people with ALK-positive advanced NSCLC, and this FDA approval in the first-line setting means that we can now extend hope to even more people,” said Andy Schmeltz, global president, Pfizer Oncology.
Despite the NSCLC market being largely dominated by Merck & Co’s Keytruda (pembrolizumab), the ALK-positive patient group is an important subset, with this type of tumour mutation occurring in around 3-5% of cases.
Follow-up ALK inhibitors are particularly crucial in this treatment setting, given that many patients experience tumour progression after initial treatment and often require a second- or third-line option.
Lorbrena is also an important follow-up to Pfizer’s older ALK inhibitor Xalkori, which has come under pressure as it faces increasing competition from Roche’s Alecensa (alectinib) and Novartis’ Zykadia (ceritinib), with both therapies having previously bested Pfizer’s first-generation ALK inhibitor in head-to-head trials.
Pfizer said in a statement that the European Medicines Agency (EMA) is also reviewing an application for Lorbrena in the first-line metastatic NSCLC indication.