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

MET-inhibitor and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) combination therapy could overcome acquired MET-mediated osimertinib resistance. We present the final PhIb TATTON (NCT02143466) analysis (Part B, n=138/Part D, n=42) assessing oral savolitinib 600 mg/300 mg once daily (QD) + osimertinib 80 mg QD 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 33-67% and 62%, and median progression-free survival (PFS) was 5.5-11.1 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.