Abstract
Lorlatinib is an oral small molecule inhibitor of anaplastic lymphoma kinase (ALK) and C-ros oncogene 1 (ROS1) kinase developed by Pfizer for the treatment of ALK-positive non-small cell lung cancer (NSCLC). Based on results from a phase I/II trial, lorlatinib received approval in Japan in September 2018 and in the USA in November 2018 for the treatment of ALK-positive NSCLC. This article summarizes the milestones in the development of lorlatinib leading to the first global approval for this indication.
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References
Zou HY, Li Q, Engstrom LD, et al. PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations. Proc Natl Acad Sci USA. 2015;112(11):3493–8.
Basit S, Ashraf Z, Lee K, et al. First macrocyclic 3rd-generation ALK inhibitor for treatment of ALK/ROS1 cancer: clinical and designing strategy update of lorlatinib. Eur J Med Chem. 2017;134:348–56.
Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 2007;448(7153):561–6.
Solomon B, Wilner KD, Shaw AT. Current status of targeted therapy for anaplastic lymphoma kinase-rearranged non-small cell lung cancer. Clin Pharmacol Ther. 2014;95(1):15–23.
Iams WT, Lovly CM. Anaplastic lymphoma kinase as a therapeutic target in non-small cell lung cancer. Cancer J. 2015;21(5):378–82.
Shaw AT, Friboulet L, Leshchiner I, et al. Resensitization to crizotinib by the lorlatinib ALK resistance mutation L1198F. N Engl J Med. 2016;374(1):54–61.
Pfizer. Lorlatinib (Lorbrena®): Japanese prescribing Information [English translation]. 2018. https://www.pmda.go.jp. Accessed 26 Nov 2018.
Pfizer. Lorbrena® (lorlatinib): US rescribing information 2018. https://www.fda.gov. Accessed 26 Nov 2018.
Pfizer. Pfizer's next-generation ALK/ROS1 inhibitor, lorlatinib, granted breakthrough therapy designation from FDA for ALK-positive metastatic non-small cell lung cancer [media release]. http://www.pfizer.com. Accessed 26 Nov 2018.
Pfizer. U.S., EU and Japan health authorities accept regulatory submissions for review of Pfizer’s third-generation ALK inhibitor lorlatinib [media release]. http://www.pfizer.com. Accessed 26 Nov 2018.
Government of Canada. Drug and health product submissions under review (SUR). 2018. https://www.canada.ca. Accessed 20 Nov 2018.
Zou HY, Friboulet L, Kodack DP, et al. PF-06463922, an ALK/ROS1 inhibitor, overcomes resistance to first and second generation ALK inhibitors in preclinical models. Cancer Cell. 2015;28(1):70–81.
Guan J, Tucker ER, Wan H, et al. The ALK inhibitor PF-06463922 is effective as a single agent in neuroblastoma driven by expression of ALK and MYCN. Dis Model Mech. 2016;9(9):941–52.
Infarinato NR, Park JH, Krytska K, et al. The ALK/ROS1 inhibitor PF-06463922 overcomes primary resistance to crizotinib in ALK-driven neuroblastoma. Cancer Discov. 2016;6(1):96–107.
Shaw AT, Felip E, Bauer TM, et al. Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial. Lancet Oncol. 2017;18(12):1590–9.
Solomon BJ, Besse B, Bauer TM, et al. Lorlatinib in patients with ALK-positive non-small-cell lung cancer: results from a global phase 2 study. Lancet Oncol. 2018;19(12):1654–67.
Ou S, Shaw A, Riely G, et al. Clinical activity of lorlatinib in patients with ROS1+ advanced non-small cell lung cancer: phase 2 study cohort EXP-6 [abstract no. OA02.03 ]. J Thorac Oncol. 2018;13(10 Suppl):S322–S3.
Shaw AT, Martini JF, Besse B, et al. Efficacy of lorlatinib in patients (pts) with advanced ALK-positive non-small cell lung cancer (NSCLC) and ALK kinase domain mutations [abstract no. CT044]. Cancer Res. 2018;78(13 Suppl).
Shaw A, Bauer T, Takahashi T, et al. First-line lorlatinib versus crizotinib for advanced anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer [abstract no. P1.13-06]. J Thorac Oncol. 2018;13(10 Suppl):S584.
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The preparation of this review was not supported by any external funding.
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During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the authors on the basis of scientific completeness and accuracy. Yahiya Y. Syed is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.
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Syed, Y.Y. Lorlatinib: First Global Approval. Drugs 79, 93–98 (2019). https://doi.org/10.1007/s40265-018-1041-0
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DOI: https://doi.org/10.1007/s40265-018-1041-0