As of August 30, 2016 Arriad had files its new drug application with the FDA for brigatinib. As of Oct 31, 2016 the FDA granted ARIAD’s request for Priority Review and has set an action date of April 29, 2017.
As of January 9, 2017 Ariad agreed to be bought by Takeda Pharmaceutical Company Limited, a Japanese company. The merger is expected to close by the end of February 2017.
Abstract e20610 is from Canada and covers 97 patients. Post Crizotinib treatment 43% received Ceritinib, 20% received chemo and 37% received no additional treatment. Median overall survival was:
0.9 months for those who received no additional treatment,
7.6 months for those who received chemo, and
20.4 months for those received Ceritinib.
Abstract 9059 basically flung that administrating an HSP90 inhibitor at the same time as Crizotinib did not delay the development of resistance to Crizotinib.
Abstract 9061 pooled data from two clinical trials. 129 patients had biopsies done after Crizotinib but before Alectinib. Plasma samples were available for all 272 patients at baseline and for about 50% at progression.
At baseline 13 functional ALK mutations were identified (5 previously unreported). At progression 3 new mutations were seen. At least 7 baseline mutations had median PFS greater than 3 months suggesting Alectinib was active against them. Mutations I1171S/N ans G1202R may occur during treatment.
As for liquid biopsy, “Tumor DNA in plasma may be a non-invasive way to monitor resistance mutations”.
Abstract 11509 covers 107 pediatric patients and their tumors. ALK alterations were found in 18 of them (not all are fusion mutations). The ages ranged from 3-16 years. 7 patients were still being treated at the data cut off. At least 4 types of cancer were treated. To quote the abstract “Crz was well tolerated” and “children can benefit from crz therapy.” I am not a doctor so I can not compare these patients side effect profile with other similar studies. Among the 8 evaluable patients there was one complete response, 3 partial responses, and 1 stable disease (for a DCR of 5/8 (62.5%)).
Abstract 9064 covers 85 patients but only 8 patients has ALK mutations and baseline biopsies collected within 14 days of progression . L1196M was most common. The study indicated that Ceritinib was potent against several known ALK mutations.