Table 2.
Selected ALK inhibitors currently in the clinic or under clinical development
| Drugs | Current phase | Toxicity | Response
|
CNS response
|
||
|---|---|---|---|---|---|---|
| Crizotinib-naïve | Crizotinib-resistant | Crizotinib-naïve | Crizotinib-resistant | |||
| Crizotinib (PF-02341066) | III | Visual disturbances, nausea, vomiting, constipation, edema | – | – | Untreated: Intracranial DCR – 56% (95% CI, 46–66) Intracranial TTP: 6.7–16.4 mo85 Treated with radiotherapy: Intracranial DCR – 62% (95% CI, 54–70) mTTP: 13.2 mo (95% CI, 9.9–NR)85 |
|
| Ceritinib (LDK378) | II/III | Diarrhea, elevated transaminases | ORR – 41/59 (66%)41 mPFS: not reached41 |
ORR – 67/121 (54.6%)41 mPFS: 6.9 mo41 |
ORR 75% (95% CI, 19.4–99.4)41 | ORR 40% (95% CI, 12.2–73.8)41 |
| Alectinib (CH542802/RO542802) | II/III | Nausea, fatigue, myalgias, neutropenia, elevated CPK | Phase I/II: ORR – 43/46 (93.5%)46 | Phase I/II: ORR – 24/44 (55%), SD – 16/44 (36%)47 | Phase I/II: ORR – 11/21 (52%)47 | |
| AP26113 | I/II | Nausea, fatigue, diarrhea | – | ORR – 24/38 (63%)86 mPFS: 47 wk86 |
– | ORR – 6/10, SD – 2/10, PD – 2/1086 |
| ASP-3026 | IB | Nausea, vomiting, constipation, abdominal pain | – | PR: 7/15 (49%), SD: 8/15 (50%)87 mPFS: 5.9 mo (95% CI 3.8–9.4)87 |
– | – |
| X-396 | I/II | N/A | 13 ALK+: 3 crizotinib-naive and 10 crizotinib-resistant – among 6 ALK + patients: SD 17% and PR 83% (unsure of crizotinib-naive or -resistant)78 | |||
Abbreviations: TTP, time to progression; CI, confidence interval; ORR, overall response rate; SD, standard deviation; PFS, progression-free survival; mPFS, median progression-free survival; ALK, anaplastic lymphoma kinase; CNS, central nervous system; CPK, creatine phosphokinase; wk, weeks; mo, months; DCR, disease control rate; NR, not reached; mTTP, median time to progression; N/A, not available; PD, progressive disease.