Table 2.

Patients with the most common all-causality AEs (≥20% across all patient groups) and dose-limiting toxicities by preferred term: safety analysis set

Adverse eventAZD6244 twice daily dose, number (%) of patients
Part APart BPart A+BTotal no. of patients (n = 56)
25 mg (n = 6)50 mg (n = 7)75 mg (n = 7)100 mg (n = 8)75 mg (n = 28)75 mg (n = 35)
Grade 1-2Grade 3-4Grade 1-2Grade 3-4Grade 1-2Grade 3-4Grade 1-2Grade 3-4Grade 1-2Grade 3-4Grade 1-2Grade 3-4
Fatigue2 (33.3)1 (16.7)4 (57.1)03 (42.9)2 (28.6)*7 (87.5)1 (12.5)14 (50.0)4 (14.3)17 (48.6)6 (17.1)38 (67.9)
Acneiform dermatitis2 (33.3)06 (85.7)02 (28.6)1 (14.3)5 (62.5)1 (12.5)17 (60.7)1 (3.6)19 (54.3)2 (5.7)35 (62.5)
Nausea4 (66.7)03 (42.9)1 (14.3)6 (85.7)04 (50.0)1 (12.5)11 (39.3)017 (48.6)030 (53.6)
Diarrhea2 (33.3)02 (28.6)06 (85.7)04 (50.0)013 (46.4)019 (54.3)027 (48.2)
Peripheral edema1 (16.7)02 (28.6)05 (71.4)04 (50.0)011 (39.3)1 (3.6)16 (45.7)1 (2.9)24 (42.8)
Cough3 (50.0)01 (14.3)04 (57.1)00011 (39.3)015 (42.9)019 (33.9)
Dry skin001 (14.3)03 (42.9)03 (37.5)012 (42.9)015 (42.9)019 (33.9)
Exertional dyspnea2 (33.3)03 (42.9)02 (28.6)0008 (28.6)1 (3.6)10 (28.6)1 (2.9)16 (28.6)
Anorexia2 (33.3)01 (14.3)0002 (25.0)010 (35.7)010 (28.6)015 (26.8)
Constipation1 (16.7)04 (57.1)02 (28.6)01 (12.5)07 (25.0)09 (25.7)015 (26.8)
Vomiting3 (50.0)01 (14.3)1 (14.3)2 (28.6)02 (25.0)04 (14.3)2 (7.1)6 (17.1)2 (5.7)15 (26.8)
Abdominal pain003 (42.9)03 (42.9)01 (12.5)05 (17.9)08 (22.9)012 (21.4)
Pruritus1 (16.7)04 (57.1)03 (42.9)01 (12.5)04 (14.3)07 (20.0)013 (23.2)
Pleural effusion00000001 (12.5)00001 (1.8)

NOTE: Part B includes 75 mg Hyd-Sulfate capsule and 100 mg free-base suspension dosing at days 1 or 8.

  • *One DLT of grade 3 fatigue was reported at 75 mg twice daily in the first 22 days of dosing.

  • One DLT of grade 3 acneiform dermatitis was reported at 100 mg twice daily in the first 22 days of dosing.

  • One DLT of grade 3 pleural effusion was reported at 100 mg twice daily in the first 22 days of dosing.