Table 2.
Overview of TEAEs and TEAEs occurring in >15% of patients by preferred term (combination safety set).
| Patients, n (%) | Berzosertib + gemcitabine (all doses), n = 50 | Berzosertib + gemcitabine + cisplatin (all doses), n = 8 | ||
|---|---|---|---|---|
| Any grade | Grades 3–4a | Any grade | Grades 3–4a | |
| TEAEs | ||||
| AEs | 49 (98.0) | 38 (76.0) | 8 (100.0) | 8 (100.0) |
| Serious AEs | 24 (48.0) | 13 (26.0) | 5 (62.5) | 5 (62.5) |
| Treatment-related AEs | ||||
| AEs | 48 (96.0) | 26 (52.0) | 8 (100.0) | 8 (100.0) |
| Serious AEs | 14 (28.0) | 4 (8.0) | 4 (50.0) | 4 (50.0) |
| AEs leading to study drug discontinuation | 9 (18.0) | 5 (10.0) | 1 (12.5) | 1 (12.5) |
| AEs leading to death | 1 (2.0)b | 0 | ||
| DLTsc | 4 (8.0) | 3 (37.5) | ||
| TEAEs occurring in ≥15% of patients in either group | Any grade | Any grade | ||
| Fatigue | 32 (64.0) | 8 (100.0) | ||
| Nausea | 31 (62.0) | 7 (87.5) | ||
| Anaemia | 26 (52.0) | 3 (37.5) | ||
| ALT increased | 25 (50.0) | 3 (37.5) | ||
| Vomiting | 22 (44.0) | 3 (37.5) | ||
| AST increased | 19 (38.0) | 3 (37.5) | ||
| Pyrexia | 18 (36.0) | 3 (37.5) | ||
| Constipation | 16 (32.0) | 3 (37.5) | ||
| Decreased appetite | 16 (32.0) | 2 (25.0) | ||
| Diarrhoea | 15 (30.0) | 3 (37.5) | ||
| Cough | 15 (30.0) | 1 (12.5) | ||
| Neutropenia | 14 (28.0) | 5 (62.5) | ||
| Headache | 13 (26.0) | 1 (12.5) | ||
| Influenza-like illness | 13 (26.0) | 0 | ||
| Lower respiratory tract infection | 13 (26.0) | 0 | ||
| Lethargy | 12 (24.0) | 3 (37.5) | ||
| Thrombocytopenia | 12 (24.0) | 3 (37.5) | ||
| Blood alkaline phosphatase increased | 11 (22.0) | 2 (25.0) | ||
| Dyspnoea | 11 (22.0) | 1 (12.5) | ||
| Back pain | 10 (20.0) | 0 | ||
| Abdominal pain upper | 7 (14.0) | 2 (25.0) | ||
| Dizziness | 6 (12.0) | 3 (37.5) | ||
| Urinary tract infection | 6 (12.0) | 3 (37.5) | ||
| Oedema peripheral | 6 (12.0) | 2 (25.0) | ||
| Leukopenia | 6 (12.0) | 2 (25.0) | ||
| Stomatitis | 6 (12.0) | 2 (25.0) | ||
| Gamma-glutamyl transferase increased | 4 (8.0) | 2 (25.0) | ||
| Myalgia | 4 (8.0) | 2 (25.0) | ||
| Abdominal discomfort | 2 (4.0) | 2 (25.0) | ||
| Grade ≥3 TEAEsd | Grade ≥3 | Grade ≥3 | ||
| Neutropenia | 8 (16.0) | 5 (62.5) | ||
| ALT increased | 8 (16.0) | 1 (12.5) | ||
| Fatigue | 8 (16.0) | 1 (12.5) | ||
| Thrombocytopenia | 5 (10.0) | 3 (37.5) | ||
| Anaemia | 5 (10.0) | 1 (12.5) | ||
AE adverse event, ALT alanine aminotransferase, AST aspartate aminotransferase, DLT dose-limiting toxicity, TEAE treatment-emergent adverse event.
aNo grade 5 AEs were observed.
bPatient had a reported serious AE of progression of non-small-cell lung cancer as the cause of death.
cIn berzosertib + gemcitabine cohorts, the following DLTs were observed: increased grade 3 ALT and grade 3 fatigue (one patient; berzosertib 72 mg/m2 + gemcitabine 875 mg/m2), increased grade 3 AST (one patient; berzosertib 90 mg/m2 + gemcitabine 500 mg/m2), increased grade 3 ALT, grade 2 AST, and grade 2 blood alkaline. phosphatase (one patient; berzosertib 140 mg/m2 + gemcitabine 500 mg/m2) and grade 4 thrombocytopenia (one patient; berzosertib 72 mg/m2 + gemcitabine 875 mg/m2). In berzosertib + gemcitabine + cisplatin cohorts, two patients in the berzosertib 120 mg/m2 cohort had DLTs (grade 4 febrile neutropenia and neutropenia); a third patient (berzosertib 90 mg/m2) had a DLT of thrombocytopenia (grade 4). All these patients also received gemcitabine 875 mg/m2 and cisplatin 60 mg/m2.
dOccurring in ≥10% of patients in the berzosertib + gemcitabine cohorts or in more than one patient in the berzosertib + gemcitabine + cisplatin cohorts.