Table 3.
Summary of PK parameters by dose level during schedule 2 and at the selected dose of 10 mg bid in the melanoma expansion cohort. Data are presented as mean (SD) values, except when noted otherwise.
| Schedule 2 (Continuous Daily Dosing) | Melanoma Expansion Cohort | |||||||
|---|---|---|---|---|---|---|---|---|
| Cycle 1 Day 1 | Cycle 2 Day 1 | Cycle 1 Day 1 | Cycle 2 Day 1 | |||||
| Dose (Daily Dose)a | 3.2 mg | 5 mg | 8 mg | 12 mg | 8 mg | 16 mg | 10 mg | 10 mg |
| n | 3 | 7 | 10 | 4 | 6 | 6 | 25 | 16 |
| tmax, hrb | 2.00 (2.00−2.50) | 2.50 (2.00−24.50) | 1.50 (1.00−4.00) | 1.50 (1.00−1.50) | 2.50 (1.50−4.00) | 2.03 (1.00−4.00) | 2.00 (1.00−4.00) | 3.00 (0.00−6.00) |
| CL/F, L/hr | ND | ND | ND | ND | 8.05 (3.89) | 6.09 (1.18) (n=4) | ND | 7.77 (3.02) (n=14) |
| Vss/F, L | ND | ND | ND | ND | 86.8 (35.7) (n=5) | 68.5 (19.0) (n=3) | ND | 75.4 (24.6) (n=10) |
| Cmax, ng/mL | 51.4 (30.5) | 62.6 (25.5) | 177 (60.6) | 232 (60.0) | 168 (73.4) | 341(176) | 167(68.8) | 209 (107) |
| AUC0-6, ng·hr/mL | 180 (68.6) | 245(115) | 613 (229) | 913 (250) | 678 (262) | 1510(677) | 608 (241) | 815(320) |
| AUC0-24, ng·hr/mL | 407.38 (120.797) | 649.70 (256.151) | 1302.75 (441.924) | 1812.17 (649.112) | 1819.57 (735.252) | 3557.51 (688.828) | 1365.39 (647.136) | 1984.94 (971.427) |
| fe, % | 0.37 (0.102) | 1.47 (0.685) | 0.83a (0.351) | 0.68 (0.283) | 1.26 (1.168) | 1.35 (0.593) | 0.45 (0.282) | 0.95 (0.987) |
a
During schedule 2, on PK days cycle 1 day 1 and cycle 2 day 1, only 1 dose of lenvatinib bid was administered.
b
Reported as median, (range)
Abbreviation: ND, not determined.