Table 5 Landmark clinical trials in the development of ALK inhibitors
From: Clinical development of targeted and immune based anti-cancer therapies
Drug Name | Clinical Trial ID | Trial Name | Population | Comparator | Year | Sponsor | Phase | N | Median OS (months) | Median PFS (months) |
|---|---|---|---|---|---|---|---|---|---|---|
ALK inhibitors | ||||||||||
 1st Generation ALK-inhibitors | ||||||||||
  Crizotinib (Xalkori®) | ||||||||||
  Crizotinib (50–2000 mg/d) | NCT00585195 | PROFILE 1001 | Advanced cancer | Rifampin, Itraconazole | 2006–2023 | Pfizer | I | 600 | NR | 9.7 |
  Crizotinib (250 mg BD) | NCT00932451 | PROFILE 1005 | NSCLC | None | 2010–2015 | Pfizer | II | 1069 | 21.8 | 8.1 |
  Crizotinib (250 mg BD) | NCT0093283 | PROFILE 1007 | NSCLC | Permetrexed or docetaxel | NR | Pfizer | III | 172 | 20.3 vs 22.8 | 7.7 vs 3.0 |
  Crizotinib (250 mg BD) | NCT01154140 | PROFILE 1014 | Non-squamous lung cancer | Platinum + permetrexed | 2011–2013 | Pfizer | III | 343 | NR | 10.9 vs 7.0 |
 Ceritinib (Zykadia®) | ||||||||||
  Ceritinib (750 mg/d) | NCT01283516 | ASCEND-1 | Tumors (ALK+) | None | 2011–2013 | Novartis | I | 304 | 16.7 | 7.0 |
  Ceritinib (750 mg/d) | NCT02336451 | ASCEND-2 | NSCLC | None | 2015–2018 | Novartis | II | 160 | NR | 5.7 |
  Ceritinib (750 mg/d) | NCT01685138 | ASCEND-3 | NSCLC | None | 2008–2018 | Novartis | II | 125 | NR | 10.8 |
  Ceritinib (750 mg/d) | NCT01828099 | ASCEND-4 | NSCLC | Chemotherapy | 2013–2016 | Novartis | III | 375 | NR | 16.6 vs 8.1 |
  Ceritinib (750 mg/d) | NCT01828112 | ASCEND-5 | NSCLC | Chemotherapy | 2013–2017 | Novartis | III | 232 | 20.1 vs 18.1 | 5.4 vs 1.6 |
  Ceritinib (750 mg/d) | NCT02299505 | ASCEND-8 | NSCLC | None | 2015–2016 | Novartis | I | 318 | NR | NR |
 Alectinib (Alcensa®) | ||||||||||
  Alectinib (600 mg BD) | NCT01871805 | NP28761 | NSCLC | None | 2013–2017 | Hoffmann-La Roche | I/II | 134 | 27.9 | 8.2 |
  Alectinib (600 mg BD) | NCT01801111 | NP28673 | NSCLC | None | 2013–2014 | Hoffmann-La Roche | I/II | 138 | 12.1 | 7.5 |
  Alectinib (600 mg BD) | NCT02075840 | ALEX | NSCLC | Crizotinib | 2014–2017 | Hoffmann-La Roche | III | 303 | NR | 25.7 vs 10.4 |
 Brigatinib (Alunbrig™) | ||||||||||
  Brigatinib (90 mg/d) | NCT01449461 |  | NSCLC | None | 2011–2015 | Ariad | I/II | 137 | NR | 16.3 |
  Brigatinib (90 mg/d) | NCT02094573 |  | NSCLC | None | 2014–2016 | Ariad | II | 222 | 46% | 9.2 |
  Brigatinib (90 mg/d) | NCT02737501 | ALTA-L1 | NSCLC | Crizotinib | 2016–2020 | Ariad | III | 275 | 85 vs 86% | 67 vs 43% |
Lorlatinib | ||||||||||
  Lorlatinib (10-200 mg/d) | NCT01970865 | CROWN | NSCLC | None | 2014–2017 | Pfizer | II | 367 | 22.3 | 5.3 |