Table 1.

Trials targeting both EGFR and MET using EGFR and MET TKIs.

EGFR TKI	MET TKI	Study (NCT ID, Name, Author, Year)	Population	Treatment	MET Alteration	N	Objective Response Rate (ORR)	Progression Free Survival (PFS)
Gefitinib	Capmatinib	NCT01610336, Wu et al., 2018 [41]	EGFR+ NSCLC acquired resistance to first- or second-generation EGFR TKI	Gefitinib 250 mg once daily + Capmatinib 400 mg twice daily	IHC 3+, IHC 2+ plus MET GCN $\ge$ 5, or MET GCN $\ge$ 4	100	29%	5.5 months
Osimertinib	Savolitinib	NCT02143466, TATTON, Sequist et al., 2020 [42]	EGFR+ NSCLC progressed after prior therapy	Osimertinib 80 mg once daily + Savolitinib 300 mg once daily	IHC 3+, MET GCN $\ge$ 5 or MET/CEP $\ge$ 2:1	138	33–67%	5.5–11.0 months
			EGFR+ T790M- NSCLC with no prior third-generation EGFR TKI			42	62%	9.0 months
Osimertinib	Savolitinib	NCT03944772, ORCHARD, Yu et al., 2021 [43]	EGFR+ advanced NSCLC with progression on first-line osimertinib	Osimertinib 80 mg once daily + Savolitinib 300 or 600 mg once daily	MET amplification or exon 14 skipping by NGS	20	41%	Not reported
Gefitinib	Savolitinib	NCT02374645, Yang et al., 2021 [44]	EGFR+ advanced NSCLC progressed on prior EGFR-TKI with MET amplification	Gefitinib 250 mg once daily + Savolitinib 600 mg once daily	MET amplification by FISH GCN $\ge$ 5 or MET/CEP $\ge$ 2:1)	51	31%	4.0 months
Erlotinib	Capmatinib	NCT01911507, McCoach et al., 2021 [45]	Advanced MET-positive NSCLC (Cohort A EGFR+)	Erlotinib 100–150 mg once daily + Capmatinib 100–600 mg twice daily	FISH GCN or MET/CEP outside of normal range, IHC 2-3+, +RT-PCR, or exon14 splice mutation	12	50%	Not reported
Gefitinib	Tepotinib	NCT01982955, INSIGHT 1, Liam et al., 2023 [46]	Advanced/metastatic EGFR+ NSCLC acquired resistance to first- or second-generation EGFR TKI T790M-, no prior MET therapy	Gefitinib 250 mg once daily + Tepotinib 500 mg once daily vs. Chemo- therapy	IHC 2+ or 3+, MET GCN $\ge$ 5, or MET/CEP $\ge$ 2:1	55	45% (vs. 33% with chemo- therapy)	4.9 months (vs. 4.4 months with chemotherapy)
					MET amplification by FISH GCN $\ge$5 or MET/CEP $\ge$2:1)	19	68% (vs. 43% with chemo- therapy)	16.6 months (vs. 4.2 months with chemo-therapy)
Osimertinib	Tepotinib	NCT03940703, INSIGHT 2, Mazieres et al., 2022 [47]	Advanced EGFR+ NSCLC with MET amplification after progression on first-line osimertinib	Osimertinib 80 mg once daily + Tepotinib 500 mg once daily	MET amplification by FISH GCN $\ge$ 5 or MET/CEP $\ge$ 2:1)	22	55%	Not reported

EGFR: Epidermal growth factor receptor; MET: Mesenchymal-epithelial transition; TKI: Tyrosine kinase inhibitor.