FDA grants Lorlatinib breakthrough therapy recognition for non small cell lung cancer

• by EVOMT
• 2017-06-05

　　Pfizer, a developer of a new generation of ALK/ROS1 tyrosine kinase inhibitors, said the FDA has granted Lorlatinib a breakthrough treatment for patients with ALK positive metastaticfile non small cell lung cancer who have previously received one or more ALK inhibitors

　　Dr. Mace Rothenberg, chief tumor researcher at Pfizer Global Product Development, said at a news conference, "This regulatory determination means that lorlatinib can provide an important treatment plan for patients with ALK positive non small cell lung cancer who develop disease progression after treatment. Pfizer's rapid development of lorlatinib also reflects Pfizer's commitment to developing biomarker driven treatment methods to meet the changing needs of patients."

　　The FDA has granted this breakthrough therapy designation to accelerate the development and review of potential new drugs for treating severe diseases, and preliminary clinical evidence suggests that the drug may have significant improvements compared to existing therapies

　　Many patients with ALK or ROS1 positive non small cell lung cancer develop resistance to tyrosine kinase inhibitors (TKIs) treatment, with the central nervous system (CNS) being the common site of relapse. Lorlatinib is a selective brain osmotic ALK/ROS1 tyrosine kinase inhibitor that can effectively inhibit most known mutations in drug resistance

　　Pfizer has submitted the results of the ongoing phase I/II clinical trial to FDA under study number NCT01970865 (54 cases in total) The study was also reported at the 17th World Lung Cancer Congress in 2016. As of January 2016, the study recruited 41 ALK positive patients, 12 ROS1 positive patients, and 1 patient had an unrecorded mutation status

　　Before joining the study, 27 patients had received at least 2 tyrosine kinase inhibitors, 20 patients had received one tyrosine kinase inhibitor, and the remaining 7 patients had not received tyrosine kinase inhibitors

　　The dosage used by patients receiving lorlatinib treatment is divided into 10 levels, ranging from 10 mg to 200 mg per day

　　The results showed that the overall response rate (ORR) of the drug was 47%, with complete response (CR) in 3 patients and partial response (PR) in 22 patients

　　The overall response rate of ALK positive patients who had received treatment with a tyrosine kinase inhibitor was 57%. Of the 14 patients in the group, 1 had complete response (7%), and 7 had partial response (50%)

　　The overall response rate of ALK positive patients who had received treatment with two or more tyrosine kinase inhibitors was 42%. Of the 26 patients in the group, 2 had complete response (8%), and 9 had partial response (34%)

　　For 39 patients with targeted and non targeted metastaticfile lesions, the overall intracranial remission rate was 36%. There were 10 patients with complete remission (26%), and 1 patient with suspected complete remission; There were also 4 cases of partial remission (10%) and 2 cases of suspected partial remission

　　For 23 patients with targeted metastaticfile lesions, the overall intracranial response rate was 47%. Among them, 7 cases had complete response (30%), 4 cases had partial response (17%), and 2 cases were suspected of partial response

　　The median duration of remission in ALK positive patients was 10.5 months, and the median duration of remission in ALK positive/ROS1 positive patients was 12.4 months

　　The most common treatment related adverse events (AEs) were hypercholesterolemia (69%) and peripheral edema (37%) Hypercholesterolemia is also the most common level 3/4 treatment related adverse event (11%) and the most common cause of dose delay or reduction. No patient has stopped taking medication due to treatment related adverse events. The researchers pointed out that the maximum acceptable dose is 100mg once a day

　　Researchers are expected to provide the latest data results at the upcoming ASCO 2017 annual meeting