Table 1.
Clinical trials with anaplastic lymphoma kinase inhibitors.
| Drug | Clinical trials | Line of therapy | Control arm | ORR | IC-ORR | PFS(m) | OS(m) |
|---|---|---|---|---|---|---|---|
| Crizotinib | PROFILE 1005 (3) | ≥2 | – | 54% | – | 8.1 | – |
| PROFILE 1007 (4) | Second line | chemotherapy | – | – | 7.7 vs 3.0 | – | |
| PROFILE 1014 (5) | First line | Platinum doublet | 74% vs 45% | NA | 10.9 vs 7.0 | 59.8 vs 19.2 | |
| PROFILE 1029 (6) | First line | Platinum doublet | 87.5% vs 45.6% | NA | 11.1 vs 6.8 | – | |
| Alectinib | Phase I/II (7) | ≥2 crizotinib-resistant | – | 22% | 52% | – | – |
| AF-001JP (8) | ≥1 ALK-TKI-naive | – | 93% | – | – | – | |
| Phase II (9) | ≥2 crizotinib-resistant | – | 50% | 57% | 8.9 | – | |
| Phase II (10) | ≥2 crizotinib-resistant | – | 48% | 52% | 8.1 | – | |
| ALUR (11) | Second line | Standard chemo | 50.6% vs 2.5% | 66.7% vs 0% | 10.9 vs 1.4 | – | |
| ALEX (12) | First line | Crizotinib | 82.9% vs 75.5% | 81% vs 50% | 34.8 vs 10.4 | NR | |
| J-ALEX (13) | First line | Crizotinib | 92% vs 79% | NA | 34.1 vs 10.2 | 68.6 vs 68 | |
| Ceritinib | ASCEND-4 (14) | First line | Platinum doublet | 73% vs 2-7% | 72.7% vs 27.3% | 16.6 vs 8.1 | NR |
| ASCEND-5 (15) | Second line | Standard chemo | 39% vs 6.9% | 35% vs 5% | 5.4 vs 1.6 | 18.1 vs 20.1 | |
| ASCEND-8 (16) | a. First line b. Prior chemotherapy and/or crizotinib |
450mg or 600mg with food vs 750 mg fasted | 78.1% vs 75.7% | – | – | – | |
| Brigatinib | ALTA (17) | Second line | 90 mg once daily vs 180 mg once daily with a 7-day lead-in at 90 mg | 46% vs 56% | 50% vs 67% | 19.6 vs 24.3 | 29.5 vs 34.1 |
| ATLA-1L (18) | First line | Crizotinib | 74% vs 62% | 78% vs 26% | 24.0 vs 11.0 | NR | |
| Ensartinib | phase 1/2 trial (19) | first-line or subsequent therapy | 225 mg once daily | 69% | 64% | 9.0 | – |
| eXalt (20) | First line | Crizotinib | 75% vs 67% | 54% vs 19% | 25.8 vs 12.7 | NR | |
| Lorlatinib | phase 2 study (21) | first-line or subsequent therapy | treatment naive (EXP1) | 90% | 75% | – | – |
| Previous crizotinib only(EXP2) | 69% | 68% | – | – | |||
| Previous crizotinib with previous chemotherapy (EXP3A) | – | – | |||||
| previous non-crizotinib ALKi, with or without chemotherapy (EXP3B) | 33% | 42% | – | – | |||
| two previous ALKi with or without chemotherapy (EXP4) | 39% | 48% | – | – | |||
| three previous ALKi with or without chemotherapy (EXP5) | – | – | |||||
| CROWN (22) | First line | Crizotinib | 76% vs 58% | 82% vs 23% | 12-months:78% vs 39% | NR |