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.
|Number of pages||16|
|Publication status||Published - 2023 Jan 1|
Bibliographical noteFunding Information:
The authors thank all the patients and their families. The study (NCT02143466) was funded by AstraZeneca, the manufacturer of the drugs savolitinib and osimertinib. The authors acknowledge Bernadette Tynan, MSc, of Ashfield MedComms, an Inizio Company, for medical writing support that was funded by Astra-Zeneca in accordance with Good Publications Practice (GPP3) guidelines (http://www.ismpp.org/gpp3).
© 2022 The Authors; Published by the American Association for Cancer Research.
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