Table 1.
Published trials with MET TKIs in NSCLC.
| Drug | Trial | Phase | Treatment | Population | N. of Patients |
Results |
|---|---|---|---|---|---|---|
| Crizotinib | PROFILE-1001 (NCT00585195) |
I | Crizotinib 250 mg BID | Advanced NSCLC with MET exon 14 skipping or MET amplification: Low (≥1.8–≤2.2 copies) Medium (≥2.2–≤4 copies) High (> 4 copies) |
65 3 14 21 |
ORR 32% PFS 7.3 months DOR 9.1 months |
| METROS (NCT02499614) |
II | Crizotinib 250 mg BID | Advanced NSCLC with MET exon 14 skipping or MET amplification (MET/CEP7 ratio >2.2) |
26 | ORR 27% PFS 4.4 months DOR 3.7 months |
|
| AcSé (NCT02034981) |
II | Crizotinib 250 mg BID | Advanced NSCLC with c-MET ≥ 6 copies or all c-MET-mutations |
25 28 |
ORR 16%; PFS 3.2 months ORR 10.7%; PFS 2.2 months |
|
| Cabozantinib | NCT01866410 | II | Cabozantinib 40 mg daily + erlotinib 150 mg daily | Advanced NSCLC with EGFR mutation and progressive disease on EGFR TKI (no MET mutations) |
37 | ORR: 10.8%; PFS: 3.6 months; OS: 13.1 months |
| NCT01708954 | II | Arm A: erlotinib 150 mg daily Arm B: cabozantinib 60 mg daily Arm C: erlotinib 150 mg + cabozantinib 40 mg |
Previously treated advanced NSCLC (MET mutations not evaluated) |
38 38 35 |
ORR: 3%; PFS: 1.8 months; OS: 5.1 months ORR: 11%; PFS: 4.3 months; OS: 9.2 months ORR: 3%; PFS: 4.7 months; OS: 13.3 months |
|
| Capmatinib | GEOMETRY mono-1 (NCT02414139) | II | Capmatinib 400 mg BID | NSCLC with: MET exon 14 skipping (1st line) |
28 | ORR: 68%; PFS: 12.4 months; DOR: 12.6 months |
|
MET exon 14 skipping (subsequent lines) |
69 | ORR: 41%; PFS: 5.4 months; DOR: 9.7 months | ||||
| MET amplification GCN ≥ 10 (1st line) | 69 | ORR: 29%; PFS: 4.1 months; DOR 8.3 months | ||||
| MET amplification GCN ≥ 10 (subsequent lines) | 15 | ORR: 40%; PFS: 4.2 months; DOR 7.5 months | ||||
| Tepotinib | VISION (NCT02864992) | II | Tepotinib 500 mg once daily | NSCLC with MET exon 14 skipping (cohort A) | 99 | ORR: 46%; PFS: 8.5 months; DOR: 11.1 months; |
| Savolitinib | NCT02897479 | II | Savolitinib 600 mg for BW ≥ 50 kg or 400 mg for BW < 50 kg |
Advanced NSCLC or pulmonary sarcomatoid carcinoma with MET exon 14 skipping |
61 | ORR 49.2%; PSF 6.9 months; DCR 93.4%; |
Abbreviations: ORR, objective response rate; OS, overall survival; PFS, progression-free survival; DOR, duration of response; DCR, disease control rate.