Summary of pharmacodynamic parameter estimates for target modulation and antitumor efficacy by PF06463922 and PF06471402 in athymic mice implanted with H3122 non–small cell lung carcinomas expressing EML4-ALKL1196M
PF06463922 and PF06471402 were administered to animals orally twice daily, 7 hours apart (studies 1 and 3) or continuously via subcutaneous infusion with ALZET osmotic pumps (studies 2 and 4).
| ALK Inhibitor | Study | Target Modulation | Antitumor Efficacy | ||
|---|---|---|---|---|---|
| EC50,in vitro | EC50,in vivo | EC60,in vivo | Tsc | ||
| nM free | |||||
| PF06463922 | 1a | 15 | 36 | 52 | 51 |
| 2 | 100 | 119 | 116 | ||
| PF06471402 | 3 | 5.6 | 20 | 32 | 27 |
| 4 | 69 | 96 | 70 | ||
EC50, drug concentration causing 50% of maximum effect; EC60, drug concentration causing 60% of maximum effect; Tsc, tumor stasis concentration.
↵a Values are cited from the previous report (Yamazaki et al., 2014).