Detection Of Kit Mutants In Circulating Tumor Dna (Ctdna) And Their Association With Ponatinib Anti-Tumor Activity In Patients (Pts) With Advanced Gastrointestinal Stromal Tumors (Gist)

10517 Background: Ponatinib is a multi-targeted tyrosine kinase inhibitor with potent preclinical activity against a broad range of clinically relevant KIT mutants, including primary-activating (especially exon 11) and secondary-resistance (including exons 17/18) mutants. Ponatinib is being evaluated in a phase 2 trial (NCT01874665), in which TKI-resistant metastatic GIST pts are enrolled in 2 cohorts based on the presence (A) or absence (B) of KIT exon 11 mutations in tumor specimens. We used ctDNA to explore the association between KIT mutation status and anti-tumor activity of ponatinib. Methods: Plasma samples were collected at baseline (BL) and every 8 wks, and a subset analyzed for 7 primary (exons 9, 11, 13) and 20 secondary (exons 13, 14, 17, 18) mutations using BEAMing. The primary trial endpoint was clinical benefit rate (CBR = CR+PR+SD at 16 wks) using modified RECIST 1.1 in cohort A. Associations between changes in ctDNA levels and tumor burden (RECIST lesions) were assessed by calculating an ...