Table 2 Treatment-related adverse events in all treated patients
|  | Phase Ia (n = 99) | Phase Ib (n = 419) | Total (n = 518) | |||
|---|---|---|---|---|---|---|
Any grade | Grade ≥ 3 | Any grade | Grade ≥ 3 | Any grade | Grade ≥ 3 | |
TRAE | 79 (79.8) | 17 (17.2) | 309 (73.7) | 66 (15.8) | 388 (74.9) | 83 (16.0) |
Severe TRAE | 13 (13.1) | 12 (12.1) | 51 (12.2) | 32 (7.6) | 64 (12.4) | 44 (8.5) |
irAEs | 60 (60.6) | 9 (9.1) | 179 (42.7) | 33 (7.9) | 239 (46.1) | 42 (8.1) |
Severe irAEs | 10 (10.1) | 10 (10.1) | 37 (8.8) | 22 (5.3) | 47 (9.1) | 32 (6.2) |
TRAE leading to dose interruption | 7 (7.1) | 5 (5.1) | 68 (16.2) | 30 (7.2) | 75 (14.5) | 35 (6.8) |
TRAE leading to drop out | 10 (10.1) | 10 (10.1) | 20 (4.8) | 16 (3.8) | 30 (5.8) | 26 (5.0) |
TRAE leading to death | 0 | 0 | 4 (1.0) | 4 (1.0) | 4 (0.8) | 4 (0.8) |
TRAEs occurring in ≥ 5% patients | ||||||
 Rash | 34 (34.3) | 1 (1.0) | 68 (16.2) | 2 (0.5) | 102 (19.7) | 3 (0.6) |
 Hypothyroidism | 22 (22.2) | 0 | 48 (11.5) | 0 | 70 (13.5) | 0 |
 Pruritus | 33 (33.3) | 0 | 36 (8.6) | 0 | 69 (13.3) | 0 |
 AST increase | 15 (15.2) | 3 (3.0) | 42 (10.0) | 3 (0.7) | 57 (11.0) | 6 (1.2) |
 Fatigue | 15 (15.2) | 0 | 41 (9.8) | 2 (0.5) | 56 (10.8) | 2 (0.4) |
 Hyperthyroidism | 14 (14.1) | 0 | 40 (9.5) | 0 | 54 (10.4) | 0 |
 ALT increase | 11 (11.1) | 2 (2.0) | 39 (9.3) | 3 (0.7) | 50 (9.7) | 5 (1.0) |
 Pyrexia | 6 (6.1) | 0 | 40 (9.5) | 0 | 46 (8.9) | 0 |
 Anemia | 0 | 0 | 44 (10.5) | 8 (1.9) | 44 (8.5) | 8 (1.5) |
 Appetite decrease | 1 (1.0) | 0 | 33 (7.9) | 3 (0.7) | 34 (6.6) | 3 (0.6) |
 Lipase increase | 5 (5.1) | 1 (1.0) | 27 (6.4) | 3 (0.7) | 32 (6.2) | 4 (0.8) |
 Nausea | 4 (4.0) | 0 | 24 (5.7) | 0 | 28 (5.4) | 0 |
irAEs occurring in ≥ 5% patients | ||||||
 Rash | 34 (34.3) | 1 (1.0) | 49 (11.7) | 2 (0.5) | 83 (16.0) | 3 (0.6) |
 Hypothyroidism | 22 (22.2) | 0 | 37 (8.8) | 0 | 59 (11.4) | 0 |
 Pruritus | 33 (33.3) | 0 | 25 (6.0) | 0 | 58 (11.1) | 0 |
 Hyperthyroidism | 14 (14.1) | 0 | 33 (7.9) | 0 | 47 (9.1) | 0 |
Severe irAEs occurring in > 1 patient | ||||||
 Immune-mediated lung disease | 2 (2.0) | 2 (2.0) | 8 (1.9) | 5 (1.2) | 10 (1.9) | 7 (1.4) |
 Immune-mediated myocarditis | 1 (1.0) | 1 (1.0) | 4 (1.0) | 4 (1.0) | 5 (1.0) | 5 (1.0) |
 Infectious pneumonia | 0 | 0 | 3 (0.7) | 3 (0.7) | 3 (0.6) | 3 (0.6) |
 AST increase | 2 (2.0) | 2 (2.0) | 1 (0.2) | 0 | 3 (0.6) | 2 (0.4) |
 Hepatic function abnormal | 0 | 0 | 3 (0.7) | 0 | 3 (0.6) | 0 |
 ALT increase | 2 (2.0) | 2 (2.0) | 0 | 0 | 2 (0.4) | 2 (0.4) |
 Immune-mediated hepatic disorder | 0 | 0 | 2 (0.5) | 2 (0.5) | 2 (0.4) | 2 (0.4) |
 Lipase increase | 0 | 0 | 2 (0.5) | 2 (0.5) | 2 (0.4) | 2 (0.4) |
 Immune-mediated myositis | 0 | 0 | 2 (0.5) | 1 (0.2) | 2 (0.4) | 1 (0.2) |
 Adrenal insufficiency | 1 (1.0) | 1 (1.0) | 1 (0.2) | 0 | 2 (0.4) | 1 (0.2) |
 Platelet count decreased | 0 | 0 | 2 (0.5) | 1 (0.2) | 2 (0.4) | 1 (0.2) |
 Immune-mediated enterocolitis | 0 | 0 | 2 (0.5) | 0 | 2 (0.4) | 0 |