Pfizer's Third-Generation ALK Inhibitor Lorbrena Receives FDA Approval for ALK-Positive Metastatic NSCLC

November 06, 2018 News /BioonBIOON/ -- Pharmaceutical GiantPfizer(Pfizer) recently announced that the U.S. Food and Drug Administration (FDA) has approved the third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) Lorbrena (lorlatinib) for the treatment of patients with ALK-positive metastatic non-small cell lung cancer (NSCLC), specifically: (1) patients whose disease has progressed after treatment with the first-generation ALK inhibitor Xalkori (crizotinib) and at least one other ALK inhibitor for metastatic disease; (2) patients who have received the second-generation ALK inhibitor alectinib (brand name: Alecensa,Novartispharmaceuticals) or certinib (brand name: Zykadia,Roche Pharmaceuticals) patients with disease progression after first-line treatment for metastatic disease.

This approval is an accelerated approval based on tumor response rate and duration of response. Further full approval for this indication will depend on the verification and description of clinical benefit in confirmatory studies. Notably, Lorbrena is also Pfizer’s second drug to receive approval within two months.FDAThe third approvedTumorThe study drug, with the other two drugs being: (1) the PARP inhibitor Talzenna (talazoparib), approved on October 16 for the treatment of patients with deleterious or suspected deleterious germline BRCA mutations (gBRCAm) who have HER2-negative locally advanced or metastaticBreast Cancerpatients; (2) the second-generation EGFR-targeted drug Vizimpro (dacomitinib), approved on September 27, for first-line treatment of NSCLC patients harboring EGFR exon 19 deletions or exon 21 L858R substitution mutations.

Xalkori, the world’s first ALK-targeted therapy launched by Pfizer, has significantly transformed the clinical management of patients with advanced ALK-positive non-small cell lung cancer (NSCLC) since its market approval in 2011. Nevertheless, lung cancer remains the leading cause of cancer-related mortality worldwide.

Although many patients with ALK-positive metastatic NSCLC respond to initial TKI therapy, disease progression typically occurs. Furthermore, therapeutic options are very limited for patients whose disease progresses after treatment with second-generation ALK-TKIs (such as alectinib, brigatinib, and ceritinib). The approval of Lorbrena will provide a new treatment option for this patient population.

This approval is based on data from the Phase I/II study B7461001, which evaluated the efficacy and safety of Lorbrena in patients with ALK-positive metastatic non-small cell lung cancer (NSCLC) who had experienced disease progression after treatment with one or more ALK tyrosine kinase inhibitors (ALK-TKIs). A total of 251 patients were enrolled in the study. The results showed an overall response rate (ORR) of 48% with Lorbrena treatment. Notably, in the subgroup of patients who had previously received two or more ALK-TKIs, the ORR increased to 57%. In this study, 69% of patients had brain metastases, among whom the intracranial response rate with Lorbrena was 60%.

Pfizer Global Product DevelopmentTumorPfizer’s Chief Development Officer, Mace Rothenberg, stated that since the initial approval in 2011 for ALK-positive NSCLCBiomarkerSince the advent of driver therapy, Pfizer scientists and clinicians have been committed to developing drugs that can further improve patient survival. The approval of Lorbrena represents a significant milestone for patients, demonstrating remarkable efficacy in a broad population with ALK-positive NSCLC, including those who have been heavily pretreated and have very limited treatment options after disease progression on first- and second-generation ALK-TKIs.

Currently, Lorbrena has also been approved in Japan for patients with ALK fusion gene-positive unresectable advanced and/or recurrent NSCLC who are resistant or intolerant to ALK-TKIs. (Bioon.com)

Original Source:U.S. FDA APPROVES LORBRENA® (LORLATINIB) FOR PREVIOUSLY-TREATED ALK-POSITIVE METASTATIC NSCLC