Abstract CT146: Sunitinib (S) in patients (Pts) with metastatic colorectal cancer (mCRC) with FLT-3 alterations: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study
Authors: Alvarez Ricardo H. , Garrett-Mayer Elizabeth , Halabi Susan , Mangat Pam K. , Baghdadi Tareq Al , Ahn Eugene R. , Chai Seungjean , Rygiel Andrew L. , Antonelli Kaitlyn R. , Islam Samiha , Bruinooge Suanna S. , Schilsky Richard L. 
Published: August 2019

Abstract
Background: TAPUR is a phase II multi-basket study evaluating the anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations known to be drug targets. S is an oral multi-kinase inhibitor that inhibits Fms-like tyrosine kinase-3 (FLT-3) in biochemical and cellular assays. Results from mCRC pts each with FLT-3 amplification treated with S are reported.
Methods: Simon’s optimal two stage design was used to test the null hypothesis of 15% response rate versus the alternative of 35%. Power and alpha were set at 85% and 10%, respectively. Response was assessed per RECIST v1.1. This design requires 10 pts in stage 1 and if &lt;2 pts have objective response (OR) or stable disease (SD) at 16 wks, the cohort is closed. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Genomic testing was performed using commercially available tests selected by sites. Treatment was determined according to protocol matching rules based on genomic inclusion criteria.
Results: Ten pts were enrolled from November 2016 to April 2018. Pts received S at a dose of 50 mg orally once daily for four weeks followed by two weeks off. All pts had mCRC with FLT-3 amplification. All pts are included in the data analysis for demographics, safety, PFS and OS (Table 1). No ORs were observed and despite observation of 2 pts with SD at 16 wks, the cohort was closed after further examination revealed both pts with SD died due to disease progression shortly after the 16 wk evaluation. Grades 3-4 AEs at least possibly related to drug are required to be reported. A single grade 3 diarrhea was reported as possibly related to S.
Conclusions: Monotherapy with S does not have sufficient clinical activity in mCRC pts with FLT-3 amplification for continued evaluation in this pt population. Other treatments should be considered for these pts, including treatments offered in clinical trials.
Table 1:Baseline demographics, clinical characteristics and outcomes by cohortSunitinib targeting FLT-3Tumor TypemCRC (N=10)Median age, yrs (range)56 (41, 71)Male, %80ECOG Performance Status, %01230700Median PFS, wks (90% CI)10.1 (7.4, 15.9)Median OS, wks (90% CI)29.5 (15.7, 39.9)Drug-related AEs, grades 3-4 (% of pts)10
Citation Format: Ricardo H. Alvarez, Elizabeth Garrett-Mayer, Susan Halabi, Pam K. Mangat, Tareq Al Baghdadi, Eugene R. Ahn, Seungjean Chai, Andrew L. Rygiel, Kaitlyn R. Antonelli, Samiha Islam, Suanna S. Bruinooge, Richard L. Schilsky. Sunitinib (S) in patients (Pts) with metastatic colorectal cancer (mCRC) with FLT-3 alterations: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT146.