CStone Pharmaceuticals announced that the investigational new drug ("IND") application of lorlatinib for the treatment of c-ros oncogene 1 ("ROS1")-positive advanced non-small cell lung cancer ("NSCLC") has been approved by the National Medical Products Administration ("NMPA") of China. This is the first pivotal study of lorlatinib for the treatment of ROS1-positive NSCLC in the world. Lorlatinib is a third-generation tyrosine kinase inhibitor ("TKI") which targets ROS1 and ALK.

With its clinical data from the CROWN study, lorlatinib has been approved by the U.S. Food and Drug Administration ("FDA"), expanded to include the first-line treatment for adults with metastatic NSCLC whose tumors are ALK-positive as detected by an FDA-approved test. This pivotal study is to evaluate the anti-tumor activity and safety of lorlatinib in patients with ROS1-postive advanced NSCLC. In a previous Phase I/II study, lorlatinib demonstrated deep and durable objective responses in patients with ROS1-positive advanced NSCLC who were TKI-naïve or failed initial treatment.

Lorlatinib is an oral macrocyclic adenosine triphosphate ("ATP") competitive small molecule inhibitor of ROS1 kinase and ALK. In preclinical studies, lorlatinib demonstrated potent and selective inhibitory activity against ROS1/ALK rearrangements, crizotinib-resistant ROS1 mutations, as well as acquired ALK mutations that are resistant to crizotinib, alectinib, ceritinib and brigatinib. Lorlatinib can also efficiently penetrate the blood-brain barrier.

Lorlatinib was approved in the United States as both first line and second line treatment for adults with metastatic NSCLC whose tumors are ALK-positive as detected by an FDA-approved test. In the European Union, lorlatinib is approved as a monotherapy for the treatment of adult patients with ALK-positive advanced NSCLC whose disease has progressed after alectinib or ceritinib as the first ALK TKI therapy, or crizotinib and at least one other ALK TKI. Previously, Pfizer conducted multiple clinical studies of lorlatinib in ALK -positive lung cancer in China and submitted an new drug application for the treatment of patients with ALK-positive advanced NSCLC in March 2021.

Lorlatinib has also demonstrated preliminary efficacy and well-tolerated safety in patients with ROS1-positive advanced NSCLC. In June 2021, CStone announced that it will work with Pfizer to jointly develop lorlatinib for ROS1- positive advanced NSCLC in Greater China region.