Osimertinib + Savolitinib to Overcome Acquired MET-Mediated Resistance in Epidermal Growth Factor Receptor–Mutated, MET-Amplified Non–Small Cell Lung Cancer: TATTON

Ryan J. Hartmaier, Aleksandra A. Markovets, Myung Ju Ahn, Lecia V. Sequist, Ji Youn Han, Byoung Chul Cho, Helena A. Yu, Sang We Kim, James Chih Hsin Yang, Jong Seok Lee, Wu Chou Su, Dariusz M. Kowalski, Sergey Orlov, Song Ren, Paul Frewer, Xiaoling Ou, Darren A.E. Cross, Nisha Kurian, Mireille Cantarini, Pasi A. Jänne

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)98-113
Number of pages16
JournalCancer Discovery
Volume13
Issue number1
DOIs
Publication statusPublished - 2023 Jan 1

Bibliographical note

Publisher Copyright:
© 2022 The Authors; Published by the American Association for Cancer Research.

All Science Journal Classification (ASJC) codes

  • Oncology

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