Background: In the INSIGHT trial primary analysis (NCT01982955; median follow‐up: 21.8 months), tepotinib (a potent, highly selective, once daily [QD] MET inhibitor) + gefitinib improved efficacy vs chemotherapy (CT) in patients (pts) with EGFR‐mutant (m) NSCLC and resistance to anti‐EGFR therapy due to METamp (Wu et al, Lancet Respir Med 2020). Here we report final analyses from INSIGHT (data cut‐off: Sept 3, 2021; median follow‐up: 57.5 months). Methods: Pts with EGFR‐m (T790M‐negative) NSCLC and anti‐EGFR resistance, with MET gene copy number (GCN) ≥5 and/or MET:CEP7 ≥2 by FISH (METamp), and/or MET IHC 2+/3+ (MET overexpression), were randomized to tepotinib 500 mg (450 mg active moiety) + gefitinib 250 mg QD or CT. Primary endpoint was progression‐free survival (PFS) per investigator. Preplanned analyses evaluated pts with METamp. Result: In 19/55 randomized pts (34.5%) with METamp (GCN ≥5, n=18; MET:CEP7 ≥2, n=13; MET IHC 3+, n=17), median age was 60.4 years, 68.4% were never‐smokers, and prior EGFR inhibitors were gefitinib (57.9%), afatinib (21.1%), erlotinib (10.5%), and icotinib (10.5%). Median duration of tepotinib + gefitinib was 11.3 months (range: 1.1‐56.5), with treatment duration >1 year in 6 pts (31.6%) and >4 years in 3 pts (15.8%). Two pts continued treatment outside the study. Tepotinib + gefitinib (n=12) improved outcomes vs CT (n=7). Respectively, median PFS was 16.6 vs 4.2 months (HR=0.13; 90% CI: 0.04, 0.43), median overall survival (OS) was 37.3 vs 13.1 months (HR=0.10; 0.02, 0.36), objective response rate was 67% vs 43% (odds ratio=2.67; 0.37, 19.56), and median duration of response was 19.9 (7.0, not estimable [ne]) vs 2.8 months (2.8, ne). Treatment‐related Grade ≥3 AEs occurred in 7 pts (58.3%) with tepotinib + gefitinib and 5 (71.4%) with CT. In pts with MET IHC 3+ (n=34; including 17 pts with METamp), tepotinib + gefitinib also improved PFS (HR 0.35; 90% CI: 0.17, 0.74) and OS (HR 0.44; 0.23, 0.84) vs CT. Conclusion: Tepotinib + gefitinib improved PFS and OS vs CT in pts with EGFR‐m NSCLC with METamp. INSIGHT 2 is evaluating tepotinib + osimertinib in this setting.