Table 3.
Safety Summary
| Patient, n (%) | 25 mg BID (n = 8) | 50 mg BID Cont’ (n = 18) | 50 mg BID Int’ (n = 9) | 75 mg Total Daily (n = 7) | 100 mg BIDa (n = 1) | 300 mg BIDa (n = 7) | Total (N = 50) |
|---|---|---|---|---|---|---|---|
| A. Treatment-Emergent Adverse Events | |||||||
| Any grade (≥10% of total patients) | |||||||
| Fatigue | 6 (75.0) | 13 (72.2) | 5 (55.6) | 4 (57.1) | 0 | 4 (57.1) | 32 (64.0) |
| Rashb | 4 (50.0) | 10 (55.6) | 1 (11.1) | 6 (85.7) | 0 | 5 (71.4) | 26 (52.0) |
| Constipation | 1 (12.5) | 8 (44.4) | 2 (22.2) | 3 (42.9) | 0 | 6 (85.7) | 20 (40.0) |
| Pruritusc | 1 (12.5) | 6 (33.3) | 5 (55.6) | 3 (42.9) | 0 | 4 (57.1) | 19 (38.0) |
| Diarrhea | 3 (37.5) | 6 (33.3) | 3 (33.3) | 3 (42.9) | 0 | 2 (28.6) | 17 (34.0) |
| Nausea | 4 (50.0) | 4 (22.2) | 4 (44.4) | 1 (14.3) | 0 | 3 (42.9) | 16 (32.0) |
| ALT elevation | 2 (25.0) | 3 (16.7) | 2 (22.2) | 2 (28.6) | 0 | 5 (71.4) | 14 (28.0) |
| Decreased appetite | 0 | 5 (27.8) | 4 (44.4) | 2 (28.6) | 0 | 2 (28.6) | 13 (26.0) |
| Headache | 5 (62.5) | 6 (33.3) | 0 | 1 (14.3) | 0 | 1 (14.3) | 13 (26.0) |
| AST elevation | 2 (25.0) | 3 (16.7) | 1 (11.1) | 1 (14.3) | 0 | 5 (71.4) | 12 (24.0) |
| Vomiting | 1 (12.5) | 5 (27.8) | 3 (33.3) | 2 (28.6) | 0 | 1 (14.3) | 12 (24.0) |
| Cough | 4 (50.0) | 3 (16.7) | 2 (22.2) | 0 | 0 | 2 (28.6) | 11 (22.0) |
| Arthralgia | 3 (37.5) | 1 (5.6) | 3 (33.3) | 1 (14.3) | 0 | 2 (28.6) | 10 (20.0) |
| Pyrexia | 2 (25.0) | 3 (16.7) | 2 (22.2) | 1 (14.3) | 0 | 1 (14.3) | 9 (18.0) |
| Abdominal pain | 2 (25.0) | 3 (16.7) | 1 (11.1) | 1 (14.3) | 0 | 1 (14.3) | 8 (16.0) |
| Insomnia | 1 (12.5) | 4 (22.2) | 0 | 2 (28.6) | 0 | 1 (14.3) | 8 (16.0) |
| Chills | 3 (37.5) | 1 (5.6) | 1 (11.1) | 1 (14.3) | 0 | 1 (14.3) | 7 (14.0) |
| Dizziness | 1 (12.5) | 3 (16.7) | 1 (11.1) | 1 (14.3) | 0 | 1 (14.3) | 7 (14.0) |
| Anemia | 1 (12.5) | 1 (5.6) | 1 (11.1) | 1 (14.3) | 0 | 2 (28.6) | 6 (12.0) |
| Myalgia | 2 (25.0) | 2 (11.1) | 0 | 0 | 0 | 2 (28.6) | 6 (12.0) |
| Hypothyroidism | 2 (25.0) | 3 (16.7) | 0 | 0 | 0 | 0 | 5 (10.0) |
| Upper respiratory tract infection | 0 | 2 (11.1) | 0 | 3 (42.9) | 0 | 0 | 5 (10.0) |
| Grade 3/4 (> 1 patient total) | |||||||
| ALT elevation | 0 | 2 (11.1) | 0 | 1 (14.3) | 0 | 5 (71.4) | 8 (16.0) |
| AST elevation | 1 (12.5) | 2 (11.1) | 0 | 1 (14.3) | 0 | 4 (57.1) | 8 (16.0) |
| Colitis | 2 (25.0) | 1 (5.6) | 1 (11.1) | 0 | 0 | 0 | 4 (8.0) |
| Fatigue | 0 | 2 (11.1) | 1 (11.1) | 0 | 0 | 0 | 3 (6.0) |
| Anemia | 0 | 0 | 1 (11.1) | 0 | 0 | 1 (14.3) | 2 (4.0) |
| Confusional state | 0 | 2 (11.1) | 0 | 0 | 0 | 0 | 2 (4.0) |
| Hyperglycemia | 0 | 1 (5.6) | 0 | 1 (14.3) | 0 | 0 | 2 (4.0) |
| Hypernatremia | 0 | 1 (5.6) | 0 | 1 (14.3) | 0 | 0 | 2 (4.0) |
| Hypotension | 0 | 2 (11.1) | 0 | 0 | 0 | 0 | 2 (4.0) |
| Pruritusc | 0 | 1 (5.6) | 0 | 0 | 0 | 1 (14.3) | 2 (4.0) |
| Urinary tract infection | 1 (12.5) | 0 | 1 (11.1) | 0 | 0 | 0 | 2 (4.0) |
| B. Immune-Related Adverse Events | |||||||
| Any grade (≥10% of total patients) | |||||||
| Rashb | 4 (50.0) | 10 (55.6) | 1 (11.1) | 5 (71.4) | 0 | 5 (71.4) | 25 (50.0) |
| ALT elevation | 2 (25.0) | 3 (16.7) | 2 (22.2) | 2 (28.6) | 0 | 5 (71.4) | 14 (28.0) |
| Pruritusc | 1 (12.5) | 5 (27.8) | 3 (33.3) | 1 (14.3) | 0 | 4 (57.1) | 14 (28.0) |
| AST elevation | 2 (25.0) | 3 (16.7) | 1 (11.1) | 1 (14.3) | 0 | 5 (71.4) | 12 (24.0) |
| Hypothyroidism | 2 (25.0) | 3 (16.7) | 0 | 0 | 0 | 0 | 5 (10.0) |
| Grade 3/4 (> 1 patient total) | |||||||
| ALT elevation | 0 | 2 (11.1) | 0 | 1 (14.3) | 0 | 5 (71.4) | 8 (16.0) |
| AST elevation | 1 (12.5) | 2 (11.1) | 0 | 1 (14.3) | 0 | 4 (57.1) | 8 (16.0) |
| Colitis | 2 (25.0) | 1 (5.6) | 1 (11.1) | 0 | 0 | 0 | 4 (8.0) |
| Pruritusc | 0 | 1 (5.6) | 0 | 0 | 0 | 1 (14.3) | 2 (4.0) |
ALT alanine aminotransferase, AST aspartate aminotransferase, BID twice daily, cont’ continuous, int’ intermittent, MedDRA Medical Dictionary for Regulatory Activities
a Epacadostat 100-mg BID and 300-mg BID dose cohorts were not re-explored in this study after protocol amendment to evaluate lower doses of epacadostat
b Rash included the following MedDRA preferred terms: rash, rash maculopapular, rash pruritic, rash generalized, and rash macular; patients were counted only once (a patient with multiple terms for rash was counted only once for the term “rash”)
c Pruritus included the following MedDRA preferred terms: pruritus and pruritus generalized; patients were counted only once (a patient with multiple terms for pruritus was counted only once for the term “pruritus”)