Osimertinib + Savolitinib to Overcome Acquired MET-Mediated Resistance in Epidermal Growth Factor Receptor-Mutated, MET-Amplified Non-Small Cell Lung Cancer: TATTON
Journal
Cancer discovery
Journal Volume
13
Journal Issue
1
Pages
98
Date Issued
2023-01-09
Author(s)
Hartmaier, Ryan J
Markovets, Aleksandra A
Ahn, Myung Ju
Sequist, Lecia V
Han, Ji-Youn
Cho, Byoung Chul
Yu, Helena A
Kim, Sang-We
Lee, Jong-Seok
Su, Wu-Chou
Kowalski, Dariusz M
Orlov, Sergey
Ren, Song
Frewer, Paul
Ou, Xiaoling
Cross, Darren A E
Kurian, Nisha
Cantarini, Mireille
Jänne, Pasi A
Abstract
MET-inhibitor and EGFR tyrosine kinase inhibitor (EGFR-TKI) combination therapy could overcome acquired MET-mediated osimertinib resistance. We present the final phase Ib TATTON (NCT02143466) analysis (Part B, n = 138/Part D, n = 42) assessing oral savolitinib 600 mg/300 mg once daily (q.d.) + osimertinib 80 mg q.d. in patients with MET-amplified, EGFR-mutated (EGFRm) advanced non-small cell lung cancer (NSCLC) and progression on prior EGFR-TKI. An acceptable safety profile was observed. In Parts B and D, respectively, objective response rates were 33% to 67% and 62%, and median progression-free survival (PFS) was 5.5 to 11.1 months and 9.0 months. Increased antitumor activity may occur with MET copy number ≥10. EGFRm circulating tumor DNA clearance on treatment predicted longer PFS in patients with detectable baseline ctDNA, while acquired resistance mechanisms to osimertinib + savolitinib were mediated by MET, EGFR, or KRAS alterations.
Subjects
TYROSINE KINASE INHIBITORS; PHASE-II PLATFORM; PATIENT; NSCLC; CRIZOTINIB; VOLITINIB; THERAPY; DISEASE; AZD9291; POTENT
SDGs
Publisher
AMER ASSOC CANCER RESEARCH
Type
journal article