Any-grade and grade 3 AEs occurring in more than 10% of patients overall
| Any-grade AE . | Dose-escalation cohort, n = 11 (%) . | Dose-expansion cohort, n = 16 (%) . | RP2/3D cohort, N = 22 (%) . | Total, N = 27 (%) . |
|---|---|---|---|---|
| All-cause | ||||
| Nausea | 8 (73) | 7 (44) | 11 (50) | 15 (56) |
| Skin and subcutaneous tissue disorders* | 6 (55) | 9 (56) | 13 (59) | 15 (56) |
| Diarrhea | 6 (55) | 8 (50) | 11 (50) | 14 (52) |
| Fatigue | 5 (45) | 9 (56) | 11 (50) | 14 (52) |
| Constipation | 4 (36) | 4 (25) | 5 (23) | 8 (30) |
| Decreased appetite | 4 (36) | 4 (25) | 6 (27) | 8 (30) |
| Hypotension | 2 (18) | 5 (31) | 6 (27) | 7 (26) |
| Peripheral edema | 3 (27) | 4 (25) | 7 (32) | 7 (26) |
| Pyrexia | 2 (18) | 5 (31) | 6 (27) | 7 (26) |
| Pain in extremity | 4 (36) | 3 (19) | 7 (32) | 7 (26) |
| Asthenia | 1 (1) | 5 (31) | 5 (23) | 6 (22) |
| Dyspnea | 3 (27) | 3 (19) | 4 (18) | 6 (22) |
| Thrombocytopenia | 2 (18) | 4 (25) | 6 (27) | 6 (22) |
| Upper respiratory tract infection | 2 (18) | 4 (25) | 6 (27) | 6 (22) |
| Contusion | 1 (1) | 4 (25) | 5 (23) | 5 (19) |
| Headache | 1 (1) | 4 (25) | 5 (23) | 5 (19) |
| Insomnia | 2 (18) | 3 (19) | 4 (18) | 5 (19) |
| Vomiting | 3 (27) | 2 (13) | 3 (14) | 5 (19) |
| Abdominal pain | 3 (27) | 1 (6) | 2 (9) | 4 (15) |
| Anemia | 2 (18) | 2 (13) | 4 (18) | 4 (15) |
| Back pain | 0 | 4 (25) | 4 (18) | 4 (15) |
| Cough | 1 (1) | 3 (19) | 4 (18) | 4 (15) |
| Dizziness | 1 (1) | 3 (19) | 4 (18) | 4 (15) |
| Dysgeusia | 1 (1) | 3 (19) | 4 (18) | 4 (15) |
| Muscular weakness | 0 | 4 (25) | 4 (18) | 4 (15) |
| Peripheral neuropathies not elsewhere classified† | 2 (18) | 2 (13) | 4 (18) | 4 (15) |
| Arthralgia | 0 | 3 (19) | 3 (14) | 3 (11) |
| Cardiac failure | 1 (1) | 2 (13) | 3 (14) | 3 (11) |
| Congestive cardiac failure | 1 (1) | 2 (13) | 3 (14) | 3 (11) |
| Dehydration | 2 (18) | 1 (6) | 2 (9) | 3 (11) |
| Dry skin | 1 (1) | 2 (13) | 3 (14) | 3 (11) |
| Fall | 0 | 3 (19) | 3 (14) | 3 (11) |
| Fluid retention | 1 (1) | 2 (13) | 2 (9) | 3 (11) |
| Hyponatremia | 1 (1) | 2 (13) | 3 (14) | 3 (11) |
| Increased blood creatinine | 1 (1) | 2 (13) | 3 (14) | 3 (11) |
| Nasal congestion | 1 (1) | 2 (13) | 3 (14) | 3 (11) |
| Drug-related | ||||
| Nausea | 5 (45) | 5 (31) | 7 (32) | 10 (37) |
| Diarrhea | 4 (36) | 5 (31) | 7 (32) | 9 (33) |
| Fatigue | 3 (27) | 4 (25) | 6 (27) | 7 (26) |
| Skin and subcutaneous tissue disorders* | 3 (27) | 4 (25) | 6 (27) | 7 (26) |
| Thrombocytopenia | 2 (18) | 4 (25) | 6 (27) | 6 (22) |
| Pyrexia | 1 (9) | 3 (19) | 4 (18) | 4 (15) |
| Peripheral neuropathies not elsewhere classified† | 2 (18) | 2 (13) | 4 (18) | 4 (15) |
| Vomiting | 2 (18) | 2 (13) | 3 (14) | 4 (15) |
| Decreased appetite | 2 (18) | 2 (13) | 3 (14) | 4 (15) |
| Abdominal pain | 3 (27) | 1 (6) | 2 (9) | 4 (15) |
| Asthenia | 1 (9) | 2 (13) | 2 (9) | 3 (11) |
| Headache | 1 (9) | 2 (13) | 3 (14) | 3 (11) |
| Anemia | 2 (18) | 1 (6) | 3 (14) | 3 (11) |
| Constipation | 2 (18) | 1 (6) | 2 (9) | 3 (11) |
| Any-grade AE . | Dose-escalation cohort, n = 11 (%) . | Dose-expansion cohort, n = 16 (%) . | RP2/3D cohort, N = 22 (%) . | Total, N = 27 (%) . |
|---|---|---|---|---|
| All-cause | ||||
| Nausea | 8 (73) | 7 (44) | 11 (50) | 15 (56) |
| Skin and subcutaneous tissue disorders* | 6 (55) | 9 (56) | 13 (59) | 15 (56) |
| Diarrhea | 6 (55) | 8 (50) | 11 (50) | 14 (52) |
| Fatigue | 5 (45) | 9 (56) | 11 (50) | 14 (52) |
| Constipation | 4 (36) | 4 (25) | 5 (23) | 8 (30) |
| Decreased appetite | 4 (36) | 4 (25) | 6 (27) | 8 (30) |
| Hypotension | 2 (18) | 5 (31) | 6 (27) | 7 (26) |
| Peripheral edema | 3 (27) | 4 (25) | 7 (32) | 7 (26) |
| Pyrexia | 2 (18) | 5 (31) | 6 (27) | 7 (26) |
| Pain in extremity | 4 (36) | 3 (19) | 7 (32) | 7 (26) |
| Asthenia | 1 (1) | 5 (31) | 5 (23) | 6 (22) |
| Dyspnea | 3 (27) | 3 (19) | 4 (18) | 6 (22) |
| Thrombocytopenia | 2 (18) | 4 (25) | 6 (27) | 6 (22) |
| Upper respiratory tract infection | 2 (18) | 4 (25) | 6 (27) | 6 (22) |
| Contusion | 1 (1) | 4 (25) | 5 (23) | 5 (19) |
| Headache | 1 (1) | 4 (25) | 5 (23) | 5 (19) |
| Insomnia | 2 (18) | 3 (19) | 4 (18) | 5 (19) |
| Vomiting | 3 (27) | 2 (13) | 3 (14) | 5 (19) |
| Abdominal pain | 3 (27) | 1 (6) | 2 (9) | 4 (15) |
| Anemia | 2 (18) | 2 (13) | 4 (18) | 4 (15) |
| Back pain | 0 | 4 (25) | 4 (18) | 4 (15) |
| Cough | 1 (1) | 3 (19) | 4 (18) | 4 (15) |
| Dizziness | 1 (1) | 3 (19) | 4 (18) | 4 (15) |
| Dysgeusia | 1 (1) | 3 (19) | 4 (18) | 4 (15) |
| Muscular weakness | 0 | 4 (25) | 4 (18) | 4 (15) |
| Peripheral neuropathies not elsewhere classified† | 2 (18) | 2 (13) | 4 (18) | 4 (15) |
| Arthralgia | 0 | 3 (19) | 3 (14) | 3 (11) |
| Cardiac failure | 1 (1) | 2 (13) | 3 (14) | 3 (11) |
| Congestive cardiac failure | 1 (1) | 2 (13) | 3 (14) | 3 (11) |
| Dehydration | 2 (18) | 1 (6) | 2 (9) | 3 (11) |
| Dry skin | 1 (1) | 2 (13) | 3 (14) | 3 (11) |
| Fall | 0 | 3 (19) | 3 (14) | 3 (11) |
| Fluid retention | 1 (1) | 2 (13) | 2 (9) | 3 (11) |
| Hyponatremia | 1 (1) | 2 (13) | 3 (14) | 3 (11) |
| Increased blood creatinine | 1 (1) | 2 (13) | 3 (14) | 3 (11) |
| Nasal congestion | 1 (1) | 2 (13) | 3 (14) | 3 (11) |
| Drug-related | ||||
| Nausea | 5 (45) | 5 (31) | 7 (32) | 10 (37) |
| Diarrhea | 4 (36) | 5 (31) | 7 (32) | 9 (33) |
| Fatigue | 3 (27) | 4 (25) | 6 (27) | 7 (26) |
| Skin and subcutaneous tissue disorders* | 3 (27) | 4 (25) | 6 (27) | 7 (26) |
| Thrombocytopenia | 2 (18) | 4 (25) | 6 (27) | 6 (22) |
| Pyrexia | 1 (9) | 3 (19) | 4 (18) | 4 (15) |
| Peripheral neuropathies not elsewhere classified† | 2 (18) | 2 (13) | 4 (18) | 4 (15) |
| Vomiting | 2 (18) | 2 (13) | 3 (14) | 4 (15) |
| Decreased appetite | 2 (18) | 2 (13) | 3 (14) | 4 (15) |
| Abdominal pain | 3 (27) | 1 (6) | 2 (9) | 4 (15) |
| Asthenia | 1 (9) | 2 (13) | 2 (9) | 3 (11) |
| Headache | 1 (9) | 2 (13) | 3 (14) | 3 (11) |
| Anemia | 2 (18) | 1 (6) | 3 (14) | 3 (11) |
| Constipation | 2 (18) | 1 (6) | 2 (9) | 3 (11) |
| Grade 3 AE . | Dose escalation, n = 11 (%) . | Dose expansion, n = 16 (%) . | Total at 4.0 mg, N = 22 (%) . | Total, N = 27 (%) . |
|---|---|---|---|---|
| All-cause | ||||
| Dyspnea | 1 (9) | 1 (6) | 2 (9) | 4 (15) |
| Fatigue | 1 (9) | 3 (19) | 3 (14) | 4 (15) |
| Skin and subcutaneous tissue disorders* | 2 (18) | 2 (6) | 3 (14) | 4 (15) |
| Cardiac failure | 1 (9) | 2 (13) | 3 (14) | 3 (11) |
| Diarrhea | 1 (9) | 2 (13) | 2 (9) | 3 (11) |
| Thrombocytopenia | 2 (18) | 1 (6) | 3 (14) | 3 (11) |
| Drug-related | ||||
| Diarrhea | 1 (9) | 2 (13) | 2 (9) | 3 (11) |
| Skin and subcutaneous tissue disorders* | 2 (18) | 1 (6) | 2 (9) | 3 (11) |
| Thrombocytopenia | 2 (18) | 1 (6) | 3 (14) | 3 (11) |
| Grade 3 AE . | Dose escalation, n = 11 (%) . | Dose expansion, n = 16 (%) . | Total at 4.0 mg, N = 22 (%) . | Total, N = 27 (%) . |
|---|---|---|---|---|
| All-cause | ||||
| Dyspnea | 1 (9) | 1 (6) | 2 (9) | 4 (15) |
| Fatigue | 1 (9) | 3 (19) | 3 (14) | 4 (15) |
| Skin and subcutaneous tissue disorders* | 2 (18) | 2 (6) | 3 (14) | 4 (15) |
| Cardiac failure | 1 (9) | 2 (13) | 3 (14) | 3 (11) |
| Diarrhea | 1 (9) | 2 (13) | 2 (9) | 3 (11) |
| Thrombocytopenia | 2 (18) | 1 (6) | 3 (14) | 3 (11) |
| Drug-related | ||||
| Diarrhea | 1 (9) | 2 (13) | 2 (9) | 3 (11) |
| Skin and subcutaneous tissue disorders* | 2 (18) | 1 (6) | 2 (9) | 3 (11) |
| Thrombocytopenia | 2 (18) | 1 (6) | 3 (14) | 3 (11) |