Table 3.
Study treatment exposure and summary of treatment-emergent adverse events in phase I patients with solid tumors or phase II patients with osteosarcoma (safety analysis set)
| Parameter | Phase I lenvatinib dose-finding cohorta |
Phase II expansion cohortb |
||
|---|---|---|---|---|
| 11 mg/m2 (n = 5) | 14 mg/m2 (n = 11) | 17 mg/m2 (n = 7) | 14 mg/m2 (N = 31) | |
| Median number of cycles received (range)c | 6 (2-23) | 2 (1-12) | 2 (2-7) | 3 (1-20) |
| Median duration of treatment, weeks (range)d | 20.1 (11.0-89.4) | 7.9 (2.0-47.7) | 8.0 (6.1-28.0) | 11.7 (0.7-76.0) |
| Median percentage of intended dose (range)e | 82.9 (58.5-100.0) | 87.0 (63.3-100.0) | 95.5 (76.4-100.0) | 96.3 (45.4-102.1) |
| Number of patients with dose reduction, n (%) | 2 (40.0) | 5 (45.5) | 3 (42.9) | 9 (29.0) |
| Cycle of first dose reduction, n (%) | ||||
| Cycle 1 | 0 | 2 (18.2) | 0 | 1 (3.2) |
| Cycle 2 | 0 | 1 (9.1) | 1 (14.3) | 6 (19.4) |
| Cycle 3 | 0 | 0 | 0 | 0 |
| Cycle 4 | 0 | 0 | 0 | 0 |
| Cycle 5 | 1 (20.0) | 0 | 1 (14.3) | 1 (3.2) |
| Cycle ≥6 | 1 (20.0) | 2 (18.2) | 1 (14.3) | 1 (3.2) |
| Number of patients with dose interruption, n (%) | 2 (40.0) | 5 (45.5) | 3 (42.9) | 13 (41.9) |
| Cycle of first dose interruption, n (%) | ||||
| 1 | 1 (20.0) | 2 (18.2) | 0 | 7 (22.6) |
| 2 | 0 | 1 (9.1) | 1 (14.3) | 2 (6.5) |
| 3 | 0 | 1 (9.1) | 0 | 0 |
| 4 | 0 | 0 | 0 | 1 (3.2) |
| 5 | 0 | 0 | 1 (14.3) | 2 (6.5) |
| ≥6 | 1 (20.0) | 1 (9.1) | 0 | 1 (3.2) |
| Median treatment interruption, days (range) | 14 (10-18) | 7 (2-18) | 1 (1-4) | 9 (1-36) |
| TEAEs, n (%) | 5 (100.0) | 11 (100.0) | 7 (100.0) | 29 (93.5) |
| Treatment-relatedf | 5 (100.0) | 8 (72.7) | 7 (100.0) | 28 (90.3) |
| Grade ≥3 TEAEs, n (%) | 4 (80.0) | 10 (90.9) | 6 (85.7) | 20 (64.5) |
| Treatment-related | 2 (40.0) | 6 (54.5) | 6 (85.7) | 7 (22.6) |
| Serious TEAEs, n (%) | 2 (40.0) | 7 (63.6) | 5 (71.4) | 21 (67.7) |
| Treatment-related | 0 | 3 (27.3) | 3 (42.9) | 9 (29.0) |
| Deathsg, n (%) | 1 (20.0) | 3 (27.3) | 1 (14.3) | 4 (12.9) |
| Treatment-related | 0 | 0 | 0 | 0 |
| TEAEs leading to drug interruption, n (%) | 3 (60.0) | 9 (81.8) | 5 (71.4) | 18 (58.1) |
| TEAEs leading to dose reduction, n (%) | 2 (40.0) | 4 (36.4) | 3 (42.9) | 9 (29.0) |
| Treatment-related | 2 (40.0) | 4 (36.4) | 3 (42.9) | 9 (29.0) |
| TEAEs leading to drug discontinuation, n (%) | 0 | 3 (27.3) | 1 (14.3) | 4 (12.9) |
| Treatment-related | 0 | 1 (9.1)h | 0 | 1 (3.2)i |
Clinical cut-off dates: 31 March 2017 (phase I) and 02 August 2018 (phase II).
Percentages are based on total number of patients within the relevant treatment group for the safety analysis set.
For each TEAE row category, a patient with two or more adverse events in that category is counted only once.
Adverse events coded using Medical Dictionary for Regulatory Activities version 21.1 and grade using Common Terminology Criteria for Adverse Events version 4.03.
TEAE, treatment-emergent adverse event.
Due to dose capping, four patients in cohort 1 received a lower dose than the planned dose level; two were assigned to the lenvatinib 11 mg/m2 group and two were assigned to the lenvatinib 14 mg/m2 group. One additional patient was assigned to the lenvatinib 14 mg/m2 group due to a dose calculation error.
Due to dose capping, eight patients received a lower dose than the planned dose of lenvatinib 14 mg/m2.
Patients who received at least one dose of lenvatinib in a cycle were counted in that cycle. Patients were counted in each applicable category.
Duration of treatment (days) defined as date of last dose of study drug minus date of first dose of study drug + 1.
Percentage of intended dose defined as dose intensity/planned dose level × 100.
Treatment-related TEAEs include adverse events that were considered by the investigator to be possibly or probably related to study drug or that had a missing causality on the case report form.
Fatal TEAEs for any cause. Fatal serious adverse events were also reported in total serious adverse events.
Grade 4 hypertension led to lenvatinib discontinuation.
Grade 3 thrombosis led to lenvatinib discontinuation.