Table 4.
Drug‐relateda AEs reported at any grade in ≥15% of the total population and/or at grade 3 in ≥5% of the total population (no drug‐related grade 4 AEs were reported)
| AE, n (%) | Phase 1, n = 14 | Phase 2, n = 50 | mITT, n = 57 | Patients who received maintenance,b n = 18 | Total, N = 64 | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| All‐grade | Grade 3 | All‐grade | Grade 3 | All‐grade | Grade 3 | All‐grade | Grade 3 | All‐grade | Grade 3 | |
| PN NECc | 10 (71) | 2 (14) | 28 (56) | 3 (6) | 33 (58) | 4 (7) | 5 (28) | 1 (6) | 38 (59) | 5 (8) |
| Fatigue | 9 (64) | 1 (7) | 22 (44) | 1 (2) | 27 (47) | 2 (4) | 2 (11) | 0 | 31 (48) | 2 (3) |
| Rashes, eruptions and exanthems NECd | 7 (50) | 3 (21) | 23 (46) | 5 (10) | 25 (44) | 6 (11) | 3 (17) | 1 (6) | 30 (47) | 8 (13) |
| Nausea | 5 (36) | 0 | 17 (34) | 1 (2) | 19 (33) | 1 (2) | 6 (33) | 1 (6) | 22 (34) | 1 (2) |
| Diarrhoea | 5 (36) | 0 | 15 (30) | 1 (2) | 18 (32) | 1 (2) | 5 (28) | 1 (6) | 20 (31) | 1 (2) |
| Peripheral oedema | 7 (50) | 1 (7) | 13 (26) | 1 (2) | 17 (30) | 2 (4) | 2 (11) | 0 | 20 (31) | 2 (3) |
| Dysgeusia | 3 (21) | 0 | 17 (34) | 0 | 18 (32) | 0 | 0 | 0 | 20 (31) | 0 |
| Insomnia | 6 (43) | 1 (7) | 13 (26) | 0 | 15 (26) | 0 | 0 | 0 | 19 (30) | 1 (2) |
| Constipation | 4 (29) | 0 | 14 (28) | 0 | 15 (26) | 0 | 0 | 0 | 18 (28) | 0 |
| Dizziness | 2 (14) | 0 | 12 (24) | 2 (4) | 14 (25) | 2 (4) | 1 (6) | 0 | 14 (22) | 2 (3) |
| Vomiting | 3 (21) | 0 | 8 (16) | 1 (2) | 9 (16) | 1 (2) | 3 (17) | 1 (6) | 11 (17) | 1 (2) |
| Anxiety | 3 (21) | 0 | 9 (18) | 1 (2) | 11 (19) | 1 (2) | 0 | 0 | 12 (19) | 1 (2) |
| Muscle spasms | 3 (21) | 0 | 9 (18) | 0 | 11 (19) | 0 | 0 | 0 | 12 (19) | 0 |
| Muscular weakness | 3 (21) | 0 | 7 (14) | 1 (2) | 9 (16) | 1 (2) | 2 (11) | 1 (6) | 10 (16) | 1 (2) |
| Hyperglycaemia | 4 (29) | 3 (21) | 4 (8) | 2 (4) | 8 (14) | 5 (9) | 2 (11) | 0 | 8 (13) | 5 (8) |
| Hyponatraemia | 1 (7) | 1 (7) | 3 (6) | 3 (6) | 3 (5) | 3 (5) | 0 | 0 | 4 (6) | 4 (6) |
| ALT increased | 2 (14) | 2 (14) | 4 (8) | 1 (2) | 4 (7) | 1 (2) | 1 (6) | 0 | 6 (9) | 3 (5) |
| Pneumonia | 1 (7) | 1 (7) | 4 (8) | 3 (6) | 5 (9) | 4 (7) | 0 | 0 | 5 (8) | 4 (6) |
| Neutrophil count decreased | 0 | 0 | 3 (6) | 3 (6) | 3 (5) | 3 (5) | 1 (6) | 1 (6) | 3 (5) | 3 (5) |
| Neutropenia | 1 (7) | 1 (7) | 4 (8) | 2 (4) | 5 (9) | 3 (5) | 0 | 0 | 5 (8) | 3 (5) |
| Thrombocytopenia | 2 (14) | 2 (14) | 2 (4) | 1 (2) | 3 (5) | 2 (4) | 0 | 0 | 4 (6) | 3 (5) |
AE, adverse event; ALT, alanine aminotransferase; mITT, modified intent to treat; NEC, not elsewhere classified; PN, peripheral neuropathy.
a
Drug‐related defined as related to any drug in the combination.
b
New‐onset AEs during cycle ≥17.
c
High‐level term, includes PN and peripheral sensory neuropathy.
d
High‐level term, includes rash, macular rash, papular rash and maculo‐papular rash.