Table 2.
Summary of AZD8186 exposure (safety analysis set).
| Study arm | AZD8186 dosing regimen | N | Relative dose intensity (mean %; SD) | Treatment cycles received (median; IQR) | Total treatment duration (days; median; range) | |
|---|---|---|---|---|---|---|
| AZD8186 monotherapy dose finding | 30 mg BID (5:2) | 7 | 96.5 (6.1) | 1.0 (1.0–2.0) | 26.0 (8–82) | 47.0 (5–597)a |
| 60 mg BID (5:2) | 6 | 98.5 (2.6) | 3.0 (2.0–4.0) | 75.0 (26–113) | ||
| 120 mg BID (5:2) | 13 | 89.1 (18.7) | 2.0 (1.0–3.0) | 40.0 (12–194) | ||
| 240 mg BID (5:2) | 6 | 99.2 (1.4) | 1.5 (1.0–2.0) | 26.0 (5–166) | ||
| 360 mg BID (5:2) | 6 | 84.7 (25.9) | 2.0 (1.0–2.0) | 40.0 (10–83) | ||
| 300 mg BID (5:2) | 2 | 37.8 (2.2) | 1.0 (1.0–1.0) | 20.5 (19–22) | ||
| 180 mg BID (5:2) | 4 | 75.2 (15.9) | 2.0 (1.5–2.5) | 41.5 (19–69) | ||
| 30 mg BID (continuous) | 4 | 89.1 (10.9) | 5.0 (4.5–6.0) | 136.5 (105–184) | ||
| 60 mg BID (continuous) | 3 | 96.2 (6.1) | 2.0 (2.0–3.0) | 37.0 (33–85) | ||
| 120 mg BID (continuous) | 5 | 83.1 (18.5) | 2.0 (2.0–3.0) | 61.0 (56–70) | ||
| 120 mg BID (2:5) | 3 | 86.6 (7.6) | 4.0 (2.0–21.0) | 104.0 (36–597) | ||
| 240 mg BID (2:5) | 4 | 94.6 (14.2) | 4.5 (2.5–9.5) | 119.0 (44–359) | ||
| AZD8186 monotherapy dose expansion | 60 mg BID (5:2) | 12 | 97.8 (3.8) | 2.0 (1.0–3.5) | 42.0 (8–145) | 59.0 (8–364)a |
| 120 mg BID (continuous) | 8 | 96.6 (9.1) | 3.0 (2.0–9.0) | 72.0 (28–364) | ||
| AZD8186 + AAP | Dose finding: 60 mg BID (5:2) | 5 | 96.9 (5.1) | 7.0 (4.0–9.0) | 186.0 (82–278) | 99.5 (5–534)a |
| Dose finding: 120 mg BID (5:2) | 11 | 86.7 (22.7) | 3.0 (2.0–6.0) | 79.0 (15–534) | ||
| Dose expansion: 120 mg BID (5:2) | 18 | 86.8 (17.7) | 4.5 (3.0–8.0) | 112.0 (5–337) | ||
| AZD8186 + vistusertib | 30 mg BID (5:2) + 100 mg vistusertib | 7 | 90.5 (8.5) | 2.0 (1.0–3.0) | 40.0 (7–390) | 42.5 (3–390)a |
| 60 mg BID (5:2) + 100 mg vistusertib | 4 | 78.4 (17.5) | 3.0 (2.5–3.5) | 78.5 (41–105) | ||
| 60 mg BID (5:2) + 125 mg vistusertib | 4 | 79.8 (14.2) | 2.0 (1.0–3.5) | 59.0 (3–110) | ||
| 120 mg BID (5:2) + 125 mg vistusertib | 10 | 77.9 (38.8) | 2.5 (1.0–4.0) | 71.5 (12–208) | ||
| 120 mg BID (5:2) + 100 mg vistusertib | 5 | 96.6 (4.5) | 2.0 (1.0–2.0) | 35.0 (16–44) | ||
Note: Dosing of AZD8186 was 5 days on, 2 days off (5:2); 2 days on, 5 days off (2:5), or continuous.
Abbreviations: AAP, abiraterone acetate plus prednisone; BID, twice daily; IQR, interquartile range; SD, standard deviation.
aOverall treatment duration.