Table 2.
AEs with severity grade ≥ 3 and DLTs
| Treatment group | Adavosertib dose (schedule) |
Any grade ≥ 3 AE, n (%) | Any treatment-related grade ≥ 3 AE, n (%) | DLT evaluable patients,a n (%) |
Any DLT, n (%) |
DLTs:b AE preferred term (CTCAE grade, G) |
|---|---|---|---|---|---|---|
| bid 1 (n = 6) | 125 mg bid (5/9) c | 4 (66.7) | 1 (16.7) | 6 (100.0) | 0 | – |
| bid 2 (n = 6) | 150 mg bid (5/9)c | 5 (83.3) | 3 (50.0) | 6 (100.0) | 2 (33.3) |
Diarrhea (G3); nausea (G2); dehydration (G3) |
| qd 1.1 (n = 5) | 200 mg qd (5/9)c | 1 (20.0) | 1 (20.0) | 5 (100.0) | 0 | – |
| qd 1.2 (n = 6) | 200 mg qd (5/2)d | 3 (50.0) | 2 (33.3) | 5 (83.3) | 0 | – |
| qd 2.1 (n = 4) | 250 mg qd (5/9)c | 2 (50.0) | 0 | 4 (100.0) | 0 | – |
| qd 2.2 (n = 3) | 250 mg qd (5/2)d | 3 (100.0) | 3 (100.0) | 3 (100.0) | 0 | – |
| qd 2.3 (n = 10) | 250 mg qd (5/2 weekly)e | 5 (50.0) | 4 (40.0) | 9 (90.0) | 2 (22.2) | Thrombocytopenia (G3); neutropenia (G3); thrombocytopenia (G2) |
| qd 3.1 (n = 4) | 300 mg qd (5/9) c | 3 (75.0) | 1 (25.0) | 4 (100.0) | 0 | – |
| qd 3.2 (n = 16) | 300 mg qd (5/2) d | 12 (75.0) | 8 (50.0) | 15 (93.8) | 2 (13.3) | Nausea (G2); weight decreased (G1); pneumonia (G3) |
| qd 3.3 (n = 2) | 300 mg (5/2 weekly)e | 1 (50.0) | 1 (50.0) | 2 (100.0) | 2 (100.0) | Thrombocytopenia (G4); nausea (G2); vomiting (G2) |
| Total (N = 62) | 39 (62.9) | 24 (38.7) | 59 (95.2) | 8 (13.6) | 12 | |
The MTDs are indicated with italics and the RP2D indicated with bold. aPatients who received less than 80% of treatment during cycle 1 (5/2 schedule) or cycles 1 and 2 (28 days for the 5/9 schedule) were not considered evaluable, unless they experienced a DLT confirmed by the scientific research team; bSome patients experienced more than one DLT. Three patients discontinued prior to receiving adavosertib and were not included in the DLT analysis set; cCohorts bid 1, bid 2, qd 1.1, 2.1 and 3.1: 5/9 schedule with dosing on days 1–5 in a 14-day cycle; dCohorts qd 1.2, 2.2, and 3.2: 5/2 schedule with dosing on days 1–5 and 8–12 in a 21-day cycle; eCohorts qd 2.3 and 3.3: 5/2 weekly schedule with dosing on days 1–5, 8–12 and 15–19 in a 21-day cycle. AE, adverse event; CTCAE, Common Terminology Criteria for Adverse Events; DLT, dose-limiting toxicity