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FDA Expands Approval of Pfizer's Lorbrena to First-Line ALK-Positive NSCLC; Approves Roche CDx

NEW YORK – The US Food and Drug Administration on Wednesday converted an earlier accelerated approval for lorlatinib (Lorbrena) to regular approval, allowing drugmaker Pfizer to market its ALK inhibitor to newly diagnosed, metastatic ALK-positive non-small cell lung cancer patients.

The FDA simultaneously approved Roche's Ventana ALK (D5F3) CDx Assay as a companion diagnostic for identifying ALK-positive NSCLC lung cancer patients who are eligible to receive lorlatinib. The immunohistochemistry test also has companion diagnostic status for use alongside previously approved ALK-targeted drugs, including alectinib (Roche's Alecensa) and crizotinib (Pfizer's Xalkori).

The agency first granted accelerated approval to lorlatinib in 2018 as a second- or third-line treatment of ALK-positive, metastatic NSCLC after patients had progressed on earlier-generation ALK inhibitors. The FDA based its decision on an observed overall response rate of 48 percent among a subgroup of ALK-positive patients enrolled in Phase I/II clinical trial, all of whom had received treatment with previous ALK inhibiting agents, including crizotinib.

Now, in confirming and expanding the earlier approval, the FDA relied on the results of a Phase III CROWN trial in which 296 newly diagnosed patients with ALK-positive metastatic NSCLC were randomized to receive treatment with either lorlatinib or crizotinib. In this study, patients treated with lorlatinib experienced improved progression-free survival compared to those on crizotinib. Specifically, patients on lorlatinib had a 72 percent reduction in the risk of disease progression or death versus patients who got crizotinib. The overall survival results from the trial were not yet mature at the time of the progression-free survival analysis.

Notably, the trial also showed that lorlatinib had activity against cancers that had metastasized to the brain. Of the 17 patients with brain metastases in the lorlatinib arm, the intracranial response rate was 82 percent, compared to 23 percent among 13 patients with brain metastases in the crizotinib arm.