Table 3. MET Inhibitors Activity in NSCLC: published trials with Selective TKIs.
| Drug | Trial | Phase | Treatment | Met-alteration | No. of pts | Efficacy outcome |
|---|---|---|---|---|---|---|
| Capmatinib | NCT01610336 | II | Gefitinib 250 mg daily + Capmatinib 400 mg bid | MET-amplified | 100 | ORR: 29%; DOR: 5.6 months; PFS: 5.5 months (in pts with GCN ≥5 and IHC 3+) |
| NCT01324479 | I | Capmatinib | MET-amplified and MET exon 14 skipping (4 pts) | 55 | ORR: 22% (for pts with MET GCN ≥6 ORR: 47%; for pts with MET exon 14 skipping ORR: 75%) | |
| NCT02414139 (GEOMETRY mono-1) | II | Capmatinib 400 mg bid | MET exon 14 skipping (in pts EGFR wt and ALK-neg) | 28 (1st line) | ORR: 68%; PFS: 9.7 months; DOR: 16.6 months | |
| 69 (2nd/3rd line) | ORR: 41%; PFS: 5.4 months; DOR: 9.7 months | |||||
| Tepotinib | NCT02864992 (VISION Cohort A) | II | Tepotinib 500 mg once daily | MET exon 14 skipping | 99 | ORR: 46%; PFS: 8.5 months; DOR: 11.1 months; OS: 17.1 months |
| NCT01982955 (INSIGHT) | Ib/II | Tepotinib 300 mg or 500 mg + gefitinib 250 mg once daily | MET overexpression/amplification having acquired resistance to EGFR inhibition | 18 (Ib); 31 (II) | Phase II: ORR: 45.2%; PFS 16.6 months | |
| Tivantinib (ARQ 197) | NCT01395758 | II | Erlotinib 150 mg daily + tivantinib 360 mg bid (ET) vs. pemetrexed or gemcitabine or docetaxel (C) | None | 51 (ET) vs. 45 (C) | ORR: 0% (ET) vs. 8.9% (C); PFS: 1.7 months (ET) vs. 4.3 months (C) |
| NCT01244191 (MARQUEE study) | III | Erlotinib 150 mg daily plus oral tivantinib 360 mg twice daily (E T) or erlotinib plus placebo (E P) | MET-amplified | 526 vs. 522 | ORR: 10.3% vs. 6.5%; OS: 8.5 vs. 7.8 months; PFS: 3.6 vs. 1.9 months. MET+: OS: 9.3 vs. 5.9 months; PFS: 3.7 vs. 1.9 months (longer OS in patients with GCN >4) | |
| NCT01580735 | II | Tivantinib 360 OR 240 mg twice daily/erlotinib 150 mg four times a day | MET-amplified | 45 | ORR 6.7%; PFS 2.7 months; OS 18.0 months (c-Met high vs. low: mPFS 4.1 vs. 1.4 months; mOS 20.7 vs. 13.9 months) | |
| NCT00777309 | II | Erlotinib 150 mg daily + tivantinib 360 mg daily vs. erlotinib + placebo | MET-amplified | 84 vs. 83 | ORR 10% vs. 7%; PFS: 3.8 vs. 2.3 months; OS 8.5 vs. 6.9 months | |
| NCT01377376 (ATTENTION) | III | Tivantinib 360 OR 240 mg twice daily/erlotinib 150 mg | MET-amplified | 154 vs. 153 | ITT: ORR 5.8% vs. 4.4%; PFS 2.9 vs. 2.0; OS 12.6 vs. 3.8 vs. 12.7 months | |
| Savolitinib | NCT02897479 | II | Savolitinib 600 mg for ≥50 kg or 400 mg <50 kg | MET exon 14 skipping | 61 | ORR was 49.2%; DCR 93.4%; PSF 6.9 months |
| NCT02143466 | Ib | Osimertinib 80 mg plus savolitinib 600 mg or 300 mg | MET-amplified + EGFR mutation | 138 | ORR 48%; PFS 7.6 months; DOR 9.5 months | |
| Osimertinib 80 mg plus savolitinib 300 mg; no previous third-generation EGFR TKI, T790M negative | 36 | ORR 64%; PFS 9.1 month; DOR 8.0 months |
ORR, overall response rate; bid, twice daily; PFS, progression free survival; OS, overall survival; TKIs, tyrosine kinase inhibitors; DOR, duration of response; GCN, gene copy number.