Lorlatinib Achieves Success in Phase III Clinical Trial as First-Line Therapy for Lung Cancer

Pfizer recently announced that the Phase III CROWN study, which evaluates Lorbrena (lorlatinib) as a first-line treatment for patients with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), has met its primary endpoint.

The Independent Data Monitoring Committee (DMC) reviewed the results in a planned interim analysis. Data demonstrated that Lorbrena significantly improved progression-free survival (PFS) compared with Xalkori (crizotinib). In this study, the safety profiles of Lorbrena and Xalkori were consistent with those observed in previous clinical trials. Results from the CROWN study will be presented at an upcoming medical conference.

Xalkori, the world’s first ALK-targeted therapy launched by Pfizer, is a first-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI). Since its approval in 2011, it has dramatically transformed the clinical management of patients with advanced ALK-positive NSCLC.

Lorbrena is a third-generation ALK-TKI. It was approved by the U.S. Food and Drug Administration (FDA) in November 2018 for the treatment of patients with ALK-positive metastatic NSCLC, specifically indicated for: (1) patients whose disease has progressed after treatment with the first-generation ALK inhibitor Xalkori and at least one other ALK inhibitor for metastatic disease; (2) patients whose disease has progressed after first-line treatment with the second-generation ALK inhibitors alectinib (brand name: Alecensa, Novartis Pharmaceuticals) or ceritinib (brand name: Zykadia, Roche Pharmaceuticals) for metastatic disease.

Lorbrena received accelerated approval from the FDA for the aforementioned indications based on tumor response rate and duration of response. The CROWN study is a confirmatory Phase III trial designed to convert this accelerated approval to full approval.

Based on the positive results from the CROWN study, Pfizer plans to share the findings with the U.S. FDA and other regulatory authorities to support full approval, and also intends to submit an application for expanding Lorbrena’s indication to include first-line treatment for treatment-naive patients with ALK-positive metastatic NSCLC.

Dr. Chris Boshoff, Chief Development Officer, Oncology, Pfizer Global Product Development, stated: “Approximately 10 years ago, we pioneered the first biomarker-driven therapy for ALK-positive NSCLC—Xalkori—which revolutionized the treatment paradigm for this disease. These top-line results from the CROWN study reinforce the significant benefits of Lorbrena demonstrated in prior research. We are pleased to soon share these data with physicians and other healthcare providers, and engage with regulatory authorities worldwide to bring this third-generation ALK inhibitor to treatment-naive patients with ALK-positive NSCLC.”