Table 2.
Ongoing trials with MET TKIs in NSCLC.
| Drug | Trial | Phase | Treatment | Drug Combined | Primary Endpoint (s) | Secondary Endpoint (s) |
|---|---|---|---|---|---|---|
| Crizotinib | Matrix (NCT02664935) |
II | Crizotinib 250 mg BD continuous dosing, 21-day cycle | - | OR, PFS, DCB | TTP, OS, Safety |
| MATCH (NCT02465060) |
II | Crizotinib 250 mg BD on days 1–28 | - | ORR | OS, PFS | |
| NCT04084717 | II | Crizotinib 250 mg BD every day of each 28-day cycle | - | ORR, PFS, OS | - | |
| Cabozantinib | NCT01639508 | II | Cabozantinib 60 mg every day of each 28-day cycle | - | ORR | PFS, OS, Safety |
| LUNG-IST-127 (NCT05613413) | II | Cabozantinib 40 mg once daily Days 1–21 + pembrolizumab 200 mg iv Q3W as maintenance therapy following 4 cycles of induction therapy with disease control | Pembrolizumab | PFS | OS, ORR, Safety | |
| NCT04310007 | II | Arm A: cabozantinib S-malate QD 21-day cycle Arm B: cabozantinib S-malate QD 21-day cycle and nivolumab Q3W Arm C: ramucirumab IV and docetaxel IV Q3W |
Nivolumab | PFS | OS, BOR, safety | |
| CABinMET (NCT03911193) |
II | Cabozantinib 60 mg daily (each 28 days) | - | ORR | PFS, OS, DCR, exploratory biomarkers | |
| Merestinib | NCT02920996 | II | Merestinib 120 mg daily (each 28 days) | - | ORR | PFS, OS, DOR, Safety |
| Glesatinib | NCT02544633 | II | Glesatinib 750 mg BD | - | ORR | PFS, OS, DOR |
| NCT02954991 | II | Glesatinib 750 mg BD + Nivolumab 240 mg IV every 2 weeks or 480 mg IV every 4 weeks |
Nivolumab | ORR | OS, PFS, Safety | |
| Capmatinb | NCT03693339 | II | Capmatinib 400 mg BD continuously dosing | - | ORR | PFS, OS, DOR |
| NCT04677595 | II | Capmatinib 400 mg BD continuously dosing | - | ORR | DOR, TTR, PFS, OS, IDCR | |
| NCT05567055 | II | Capmatinib 400 mg BD continuously dosing | - | CNS Overall response rate | DOR, PFS, OS, CNS DOR, CNS PFS | |
| Geometry-N (NCT04926831) |
II | Capmatinib 400 mg BD (neoadjuvant/adjuvant setting) | - | MPR | PCR, ORR, DFS, Safety | |
| NCT04427072 | II | Capmatinib 400 mg BD | - | PFS | ORR, DOR, DCR, IDCR, OS | |
| Tepotinib | NCT04739358 | I/II | Tepotinib daily in cycles of 21-day duration | Other TKIs | Intracranial ORR, Overall and extracranial ORR | Overall, intracranial and extracranial ORR, PFS, DOR and DCR, safety |
| NCT03940703 | II | Tepotinib 500 mg once daily and osimertinib 80 mg once daily each 21 day | Osimertinib | ORR, Safety | PFS, OS | |
| POTENT NCT05782361 | I | Tepotinib 500 mg or 250 mg once daily and pembrolizumab 200 mg Q3W | Pembrolizumab | Antitumor activity | Safety, tolerability | |
| Savolitinib | NCT04923945 | III | Savolitinib 600 mg once daily continuously in patients with BW ≥ 50 kg and Savolitinib 400 mg once daily in patients with BW < 50 kg | - | ORR | PFS, Safety |
| NCT05777278 | I/II | Savolitinib 300 mg or 200 mg BD and Docetaxel 60 mg/m2 iv Q3W | Docetaxel | ORR | PFS, OS, DCR, DOR | |
| NCT05374603 | II | Savolitinib 600 mg for BW ≥ 50 kg, 400 mg for BW < 50 kg once daily and Durvalumab 1500 mg iv Q4W | Durvalumab | PFS | ORR, DOR, DCR, OS | |
| SAVANNAH NCT03778229 |
II | Savolitinib 300 mg once daily or 300 mg BD or 600 mg once daily and osimertinib 80 mg oral once daily | Osimertinib | ORR | PFS, OS, DOR | |
| SAFFRON NCT05261399 | III | Arm A: Pemetrexed (500 mg/m2) with either cisplatin (75 mg/m2) or carboplatin (AUC5) Q3W for 4 cycles, followed by pemetrexed maintenance (500 mg/m2) Q3W Arm B: Savolitinib 300 mg BD + osimertinib 80 mg once daily |
Osimertinib | PFS | OS, ORR, DCR, DOR | |
| ORCHARD NCT03944772 | II | Savolitinib 300 mg or 600 mg once daily + Osimertinib 80 mg once daily | Osimertinib | ORR | PFS, DOR, OS | |
| SACHI NCT05015608 |
III | Savolitinib once daily + Osimertinib once daily (every 3 weeks) | Osimertinib | PFS | ORR, OS, DOR, DCR, TTR, Safety | |
| FLOWERS NCT05163249 | II | Savolitinib 300 mg BD+, Osimertinib 80 mg once daily | Osimertinib | ORR | PFS, DOR, DCR, OS | |
| SANOVO NCT05009836 | III | Savolitinib 600 mg or 400 mg once daily + Osimertinib 80 once daily (every 3 weeks) | Osimertinib | PFS | ORR, OS, DOR, DCR, TTR, Safety | |
| APL-101 | SPARTA NCT03175224 |
I/II | APL-101 28-day cycles at four planned dose levels (100 mg, 200 mg, 300 mg and 400 mg) |
- | Safety, ORR | ORR, DOR, PFS, TTP |
| Elzovantinib or TPX-0022 | SHIELD-1 NCT03993873 |
I/II | Elzovantinib | - | Safety, tolerability | PFS, OS, ORR, DOR, TTR |
| GluMETinib or SCC244 | GLORY, NCT04270591 | I/II | Glumetinib 300 mg once daily | - | ORR | DOR, OS |
Abbreviations: ORR, objective response rate; OS, overall survival; PFS, progression-free survival; DOR, duration of response; DCR, disease control rate; DCB, durable clinical benefit; TTP, time to progression; CNS, central nervous system; BOR, best objective response; TTR, time to response; IDCR, intracranial disease control rate.