Table 2.
Advances of ALK/ROS1-TKIs
| Drug | Brand name | Manufacturer | Targets | Applications of diseases | Approved years or current phases of clinical trials |
|---|---|---|---|---|---|
| Crizotinib | Xalkori | Pfizer Inc | ALK, ROS1, MET | Locally advanced or metastatic ALK + NSCLC | 2011 [50] |
| Metastatic ROS1 + NSCLC | 2016 [67] | ||||
| Advanced METex14 + or MET-amplified NSCLC | ongoing [134, 135] | ||||
| Alectinib | Alecensa | Genentech Inc | ALK | Unresectable, advanced or recurrent ALK + NSCLC | 2014§ |
| 2L metastatic ALK + NSCLC, 1L metastatic ALK + NSCLC | 2015, 2017 [55, 56] | ||||
| Ceritinib | Zykardia | Novartis | ALK, ROS1 | 2L metastatic ALK + NSCLC | 2014 |
| 1L metastatic ALK + NSCLC | 2017 [198] | ||||
| Advanced ROS1 + NSCLC | II [199] | ||||
| Brigatinib | Alunbrig | Takeda | ALK | 2L metastatic ALK + NSCLC | 2017 |
| 1L metastatic ALK + NSCLC | 2020 [58, 59] | ||||
| Combined with cetuximab for EGFR/T790M/cis-C797S NSCLC | [43] | ||||
| Ensartinib | - | Beta/Xcovery Holdings Inc | ALK | 2L metastatic ALK + NSCLC | 2019 a priority review by NMPA [52] |
| Entrectinib | Rozlytrek | Genentech Inc | ROS1, TRK, ALK | Metastatic ROS1 + NSCLC | 2019 [68] |
| TRK fusion + solid tumors | 2019 [200] | ||||
| Lorlatinib | Lorbrena | Pfizer Inc | ALK, ROS1 | 2-3L metastatic ALK + NSCLC | 2018§ [64] |
| Investigational drugs | |||||
| Repotrectinib | - | Turning Point | ROS1, TRK, ALK | Advanced ROS1 + NSCLC | I [70] |
| DS-6051b | - | Daiichi Sankyo | ROS1, TRK | ROS1 + NSCLC | I [72] |
| TRK + /ROS1 + solid tumors | I [201] | ||||
| WX-0593 | - | Qilun | ALK, ROS1 | ALK + or ROS1+ NSCLC | I [61] |
| CT-707 | - | Centaurus | ALK, FAK, Pyk2 | 2L advanced ALK + NSCLC | I [62] |
| CT-3505 | - | Shouyao Holdings | ALK | ALK + NSCLC | I (ChiCTR1900025619) |
In the last column of “Approved years or current phases of clinical trials”, if a drug has been approved, we provided data of the year of its approval by Food and Drug Administration (FDA), except alectinib and lorlatinib with a superscript “§” which means they were firstly approved by Ministry of Health, Labor and Welfare (MHLW); if a drug is under investigation, we provided current phases of its clinical trials
FAK focal adhesion kinase, Pyk2 proline-rich tyrosine kinase-2, EMA European Medicines Agency, NMPA National Medical Products Administration, ALK anaplastic lymphocyte kinase, ROS1 ROS proto-oncogene 1
Data source: www.fda.gov, www.drugs.com, and www.clinicaltrials.gov (cutoff date: 19 July 2020)