Pfizer Inc. announced that the US Food and Drug Administration (FDA) has approved LORBRENA [lor-BREN-ah] (lorlatinib), a third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) for patients with ALK-positive metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on crizotinib and at least one other ALK inhibitor for metastatic disease; or whose disease has progressed on alectinib or ceritinib as the first ALK inhibitor therapy for metastatic disease.

Over the years, Pfizer has transformed research, management and treatment for patients with ALK-positive non-small cell lung cancer. Building on our extensive understanding of tumor complexity and treatment resistance, LORBRENA was discovered by Pfizer scientists and developed specifically to inhibit tumor mutations that may drive resistance to other ALK tyrosine kinase inhibitors, said Andy Schmeltz.

LORBRENA

We believe that LORBRENA will benefit patients with ALK-positive metastatic non-small cell lung cancer that have progressed on prior therapy and continue to deliver on our commitment to addressing unmet needs of cancer patients.

Since Pfizer introduced XALKORI (crizotinib) as the first TKI for the treatment of ALK-positive metastatic NSCLC in 2011, the availability of these medicines has created an opportunity to provide patients with treatment options other than chemotherapy. However, lung cancer remains the leading cause of cancer-related death around the world.

While many ALK-positive metastatic NSCLC patients respond to initial TKI therapy, they typically experience tumor progression. Additionally, options for patients who progress after treatment with second-generation ALK TKIs, alectinib, brigatinib and ceritinib, are limited. The approval of LORBRENA represents a new option for patients who have progressed on a second-generation ALK TKI, providing an opportunity to remain on oral therapy.

The last decade has witnessed dramatic improvements in the metastatic treatment ALK-positive non-small cell lung cancer due to previous generation ALK biomarker-driven therapies. Yet almost all patients still relapse due to drug resistance, with a large proportion of patients developing new or worsening brain metastases, said Alice T. Shaw.

ALK biomarker-driven therapies

In a clinical study which included patients with or without brain metastases, LORBRENA demonstrated clinical activity in patients with metastatic ALK-positive non-small cell lung cancer who had failed other ALK biomarker-driven therapies.

The approval was based on a non-randomized, dose-ranging and activity-estimating, multi-cohort, multicenter Phase 1/2 study, B7461001, evaluating LORBRENA for the treatment of patients with ALK-positive metastatic NSCLC, who were previously treated with one or more ALK TKIs. A total of 215 patients with ALK-positive metastatic NSCLC were enrolled across several subgroups based on prior treatment.

Since the beginning of the biomarker-driven treatment for ALK-positive non-small cell lung cancer in 2011, Pfizer scientists and clinicians have remained committed to research and developing medicines, said Mace Rothenberg.

LORBRENAs approval is an important milestone for patients, having demonstrated marked activity in a study that included a broad range of individuals with ALK-positive non-small cell lung cancer. This included patients who were heavily pretreated and facing limited options after receiving first- and second-generation ALK tyrosine kinase inhibitors.