Table 2 Overview of TEAEs and TEAEs occurring in >15% of patients by preferred term (combination safety set).

From: Phase 1 study of the ATR inhibitor berzosertib (formerly M6620, VX-970) combined with gemcitabine ± cisplatin in patients with advanced solid tumours

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)

  1. AE adverse event, ALT alanine aminotransferase, AST aspartate aminotransferase, DLT dose-limiting toxicity, TEAE treatment-emergent adverse event.
  2. aNo grade 5 AEs were observed.
  3. bPatient had a reported serious AE of progression of non-small-cell lung cancer as the cause of death.
  4. 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.
  5. dOccurring in ≥10% of patients in the berzosertib + gemcitabine cohorts or in more than one patient in the berzosertib +  gemcitabine + cisplatin cohorts.
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