Iclusig ponatinib: Phase II data

Data from 22 evaluable GIST patients whose tumors have an activating mutation in exon 11 of stem cell factor ( SCF) receptor tyrosine kinase (c-Kit; KIT; CD117) in cohort A of an ongoing, open-label, U.S. Phase II trial showed that once-daily 45 mg oral Iclusig led to a CBR at week 16, the primary endpoint, of 50% at a median follow-up of 6 months. Median PFS was 7 months and the ORR was 9%, including 2 partial responses. Cohort B of the trial enrolled GIST patients whose tumors have activating mutations other than the c-Kit mutation in exon 11. In 11 evaluable patients in cohort B, Iclusig led to a CBR of 27%, median PFS of 4 months and an ORR of 0%. The 6-month OS rate was 80% in cohort A and 71% in cohort B. Median OS has not been reached. Additionally, there were 14 cases of stable disease in cohort A and 6 cases of stable disease in cohort B.

The most common serious adverse events reported were abdominal pain, fatigue, nausea and vomiting. The trial enrolled patients with refractory metastatic or unresectable GIST after prior failure of >=1 TKI. Data were presented at the American Society of Clinical Oncology meeting in Chicago. Primary c-Kit mutations occur in about 85% of patients with GIST and the most common mutation is on exon 11 (about 70%), according to Ariad. The company said the data form the basis for planning registration studies of ponatinib in patients with refractory GIST, but declined to disclose details or a time frame for then the trials will begin. Ariad also said that FDA lifted the partial clinical hold on all trials of Iclusig and new patient enrollment in the Phase II GIST trial is ongoing. ...