Abstract CT032: TATTON Phase Ib expansion cohort: Osimertinib plus savolitinib for patients (pts) with EGFR-mutant, MET-amplified NSCLC after progression on prior first/second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)
Authors: Yu Helena , Ahn Myung-Ju , Kim Sang-We , Cho Byoung Chul , Sequist Lecia , Orlov Sergey , Ottesen Lone H. , Verheijen Remy B. , Mellemgaard Anders , Wessen Jonathan , Han Ji-Youn 
Published: August 2019

Abstract
After EGFR T790M, the second most common driver of acquired resistance to EGFR-TKIs in pts with EGFR-mutant NSCLC is MET-amplification. MET-amplification is seen in 5-30% of pts with resistance across various case series’. Savolitinib (volitinib, HMPL-504, AZD6094) is an oral, potent and highly selective MET-TKI. Preliminary findings from the expansion phase of the open-label, multi-center, Phase I TATTON study (NCT02143466) demonstrated acceptable safety and preliminary anti-tumor activity with savolitinib plus osimertinib in pts with EGFR-mutant NSCLC. Here we report updated interim data from this expansion phase in pts with EGFR-mutant, T790M negative, MET-amplified NSCLC who had progressed on prior first/second-generation EGFR-TKI.
Pts included in this analysis were treated with osimertinib 80 mg QD plus savolitinib 600 mg QD and met the following inclusion criteria: ≥18 years; confirmed EGFR-mutant T790M negative, locally advanced or metastatic NSCLC; progressed on ≥1 prior first/second-generation EGFR-TKI (no prior third-generation EGFR-TKIs allowed); WHO performance status 0-1. Pts were initially enrolled based on local testing for MET-positive status (NGS, FISH [MET gene copy ≥5 or MET/CEP7 ratio ≥2], or immunohistochemistry [+3 in ≥50% of tumor cells]). Primary objective was safety and tolerability; secondary objectives included assessment of anti-tumor activity (RECIST v1.1).
At data cut-off (Feb 2018), 46 pts had received study treatment. Median age was 59 years (range 41-92), 31 (67%) pts were female, and 37 (80%) were Asian. The most common (≥20%) all-causality adverse events (AEs) were nausea (n=17, 37%), diarrhea (n=14, 30%), fatigue (n=13, 28%), decreased appetite (n=13, 28%), pyrexia (n=12, 26%), and vomiting (n=10, 22%). Serious AEs were reported in 17 (37%) pts. Treatment-related AEs were reported in 42 (91%) pts and were classified as CTCAE grade ≥3 in 20 (43%) pts. Sixteen (35%) pts had an AE leading to discontinuation of study treatment. Two (4%) pts died due to an AE (n=1 acute kidney injury considered possibly related to savolitinib; n=1 pneumonia considered unrelated to study treatment). Objective response rate was 52% (n=24 all partial responses, confirmed after 4 weeks). Median duration of response was 7.1 months.
Savolitinib plus osimertinib had an acceptable safety profile and demonstrated preliminary anti-tumor activity. These findings warrant further investigation of this combination in pts with EGFR-mutant, T790M negative, MET-amplified NSCLC who progressed on prior first/second-generation EGFR-TKI treatment.
Citation Format: Helena Yu, Myung-Ju Ahn, Sang-We Kim, Byoung Chul Cho, Lecia Sequist, Sergey Orlov, Lone H. Ottesen, Remy B. Verheijen, Anders Mellemgaard, Jonathan Wessen, Ji-Youn Han. TATTON Phase Ib expansion cohort: Osimertinib plus savolitinib for patients (pts) with EGFR-mutant, MET-amplified NSCLC after progression on prior first/second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) [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 CT032.