The Food and Drug Administration (FDA) has accepted for Priority Review the supplemental New Drug Application (sNDA) for lorlatinib (Lorbrena®; Pfizer) as a first-line treatment for patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC).

The sNDA submission is supported by data from the randomized, open-label phase 3 CROWN study, which compared lorlatinib to crizotinib in 296 adults with previously untreated advanced ALK-positive NSCLC. Patients were randomized to receive lorlatinib (n=149) or crizotinib (Xalkori; Pfizer) monotherapy (n=147). The primary end point was progression-free survival (PFS); key secondary end points included objective response and intracranial response.

Results showed a greater percentage of patients treated with lorlatinib were alive without disease progression at 12 months compared with crizotinib, 78% (95% CI, 70-84) vs 39% (95% CI, 30-48), respectively (hazard ratio for disease progression or death, 0.28; 95% CI, 0.19-0.41; P <.001). Additionally, an objective response was observed in 76% of lorlatinib-treated patients (95% CI, 68-83) vs 58% (95% CI, 49-66) of crizotinib-treated patients.

Among patients with measurable brain metastases, 82% (95% CI, 57-96) of patients treated with lorlatinib achieved intracranial response compared with 23% (95% CI, 5-54) for crizotinib; 71% of lorlatinib-treated patients had an intracranial complete response.

Lorlatinib, a tyrosine kinase inhibitor, is marketed under the brand name Lorbrena and is currently approved for the treatment of ALK-positive metastatic NSCLC in patients whose disease has progressed on crizotinib and at least 1 other ALK inhibitor for metastatic disease; or alectinib as the first ALK inhibitor therapy metastatic disease; or ceritinib as the first ALK inhibitor therapy for metastatic disease.

A Prescription Drug User Fee Act (PDUFA) target date of April 2021 has been set for review of the first-line treatment indication.

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1.    Lorbrena® (lorlatinib) sNDA in previously untreated ALK-positive lung cancer accepted for Priority Review by U.S. FDA. [press release]. New York, NY: Pfizer, Inc.; December 28, 2020. 

2.    Shaw AT, Bauer TM, de Marinis F, et al. First-Line Lorlatinib or Crizotinib in Advanced ALK-Positive Lung CancerN Engl J Med. [Published online November 19, 2020]. doi: 10.1056/NEJMoa2027187.