Table 2.
Treatment-related adverse events reported in at least 2 patients (any arm) and treatment-related serious adverse eventsa
| Treatment-Related Adverse Events |
NIVO3
(n = 10) |
NIVO1+IPI3
(n = 10) |
NIVO3+IPI1
(n = 20) |
|||
|---|---|---|---|---|---|---|
| Any Grade | Grade 3/4 | Any Grade | Grade 3/4 | Any Grade | Grade 3/4 | |
| Any TRAE, n (%) | 9 (90) | 0 | 10 (100) | 9 (90) | 20 (100) | 6 (30) |
| TRAEs reported in ≥2 patients in any arm, n (%) | ||||||
| Neurological disorders | ||||||
| Headache | 2 (20) | 0 | 3 (30) | 0 | 4 (20) | 0 |
| Dizziness | 1 (10) | 0 | 0 | 0 | 3 (15) | 1 (5) |
| Gastrointestinal disorders | ||||||
| Diarrhea | 1 (10) | 0 | 7 (70) | 3 (30) | 6 (30) | 1 (5) |
| Nausea | 3 (30) | 0 | 3 (30) | 0 | 3 (15) | 0 |
| Vomiting | 1 (10) | 0 | 4 (40) | 0 | 3 (15) | 0 |
| Colitis | 0 | 0 | 2 (20) | 2 (20) | 1 (5) | 1 (5) |
| General disorders and administration-site conditions | ||||||
| Fatigue | 3 (30) | 0 | 8 (80) | 1 (10) | 11 (55) | 3 (15) |
| Asthenia | 0 | 0 | 0 | 0 | 3 (15) | 0 |
| Gait disturbance | 2 (20) | 0 | 0 | 0 | 1 (5) | 0 |
| Pyrexia | 0 | 0 | 1 (10) | 0 | 2 (10) | 0 |
| Investigations | ||||||
| Lipase increased | 2 (20) | 0 | 5 (50) | 5 (50) | 2 (10) | 0 |
| ALT increased | 0 | 0 | 4 (40) | 2 (20) | 4 (20) | 2 (10) |
| AST increased | 0 | 0 | 5 (50) | 1 (10) | 3 (15) | 2 (10) |
| Amylase increased | 1 (10) | 0 | 3 (30) | 1 (10) | 1 (5) | 0 |
| Platelet count decreased | 0 | 0 | 0 | 0 | 3 (15) | 0 |
| Lymphocyte count decreased | 0 | 0 | 0 | 0 | 2 (10) | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| Rash | 2 (20) | 0 | 1 (10) | 0 | 5 (25) | 0 |
| Pruritus | 2 (20) | 0 | 0 | 0 | 5 (25) | 0 |
| Maculopapular rash | 0 | 0 | 4 (40) | 0 | 0 | 0 |
| Endocrine disorders | ||||||
| Hyperthyroidism | 1 (10) | 0 | 3 (30) | 0 | 1 (5) | 0 |
| Hypothyroidism | 2 (20) | 0 | 1 (10) | 0 | 1 (5) | 0 |
| Blood and lymphatic system disorders | ||||||
| Anemia | 0 | 0 | 0 | 0 | 2 (10) | 0 |
| Eye disorders | ||||||
| Optic nerve disorder | 2 (20) | 0 | 0 | 0 | 0 | 0 |
| Metabolism and nutrition disorders | ||||||
| Appetite decreased | 0 | 0 | 2 (20) | 1 (10) | 1 (5) | 0 |
| Psychiatric disorders | ||||||
| Confusional state | 1 (10) | 0 | 2 (20) | 1 (10) | 2 (10) | 0 |
| Respiratory, thoracic, and mediastinal disorders | ||||||
| Cough | 0 | 0 | 1 (10) | 0 | 2 (10) | 0 |
| Any TRSAE, n (%) | 2 (20) | 0 | 7 (70) | 7 (70) | 5 (25) | 2 (10) |
| Neurological disorders | ||||||
| Headache | 0 | 0 | 0 | 0 | 1 (5) | 0 |
| Gastrointestinal disorders | ||||||
| Colitis | 0 | 0 | 2 (20) | 2 (20) | 1 (5) | 1 (5) |
| Diarrhea | 0 | 0 | 2 (20) | 2 (20) | 1 (5) | 1 (5) |
| Pancreatitis | 0 | 0 | 1 (10) | 1 (10) | 0 | 0 |
| Vomiting | 0 | 0 | 0 | 0 | 1 (5) | 0 |
| Investigations | ||||||
| ALT increased | 0 | 0 | 2 (20) | 2 (20) | 1 (5) | 1 (5) |
| AST increased | 0 | 0 | 1 (10) | 1 (10) | 1 (5) | 1 (5) |
| Lipase increased | 0 | 0 | 1 (10) | 1 (10) | 0 | 0 |
| Bilirubin increased | 0 | 0 | 1 (10) | 0 | 0 | 0 |
| Metabolism and nutrition disorders | ||||||
| Appetite decreased | 0 | 0 | 1 (10) | 1 (10) | 0 | 0 |
| Diabetic ketoacidosis | 0 | 0 | 1 (10) | 1 (10) | 0 | 0 |
| Hyperglycemia | 0 | 0 | 1 (10) | 1 (10) | 0 | 0 |
| Hypocalcemia | 0 | 0 | 1 (10) | 1 (10) | 0 | 0 |
| Hypomagnesemia | 0 | 0 | 1 (10) | 0 | 0 | 0 |
| Endocrine disorders | ||||||
| Hypothyroidism | 1 (10) | 0 | 1 (10) | 0 | 0 | 0 |
| Autoimmune thyroiditis | 0 | 0 | 0 | 0 | 1 (5) | 0 |
| Hyperthyroidism | 0 | 0 | 1 (10) | 0 | 0 | 0 |
| General disorders and administration-site conditions | ||||||
| Chest pain | 1 (10) | 0 | 0 | 0 | 0 | 0 |
| Hepatobiliary disorders | ||||||
| Cholecystitis | 0 | 0 | 1 (10) | 1 (10) | 0 | 0 |
| Infections and infestations | ||||||
| Sepsis | 0 | 0 | 1 (10) | 1 (10) | 0 | 0 |
| Psychiatric disorders | ||||||
| Confusional state | 0 | 0 | 1 (10) | 1 (10) | 0 | 0 |
| Renal and urinary disorders | ||||||
| Acute kidney injury | 0 | 0 | 1 (10) | 1 (10) | 0 | 0 |
| Respiratory, thoracic, and mediastinal disorders | ||||||
| Pneumonitis | 1 (10) | 0 | 0 | 0 | 1 (5) | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| Dermatitis bullous | 0 | 0 | 1 (10) | 0 | 0 | 0 |
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; NIVO3, nivolumab 3 mg/kg; NIVO1+IPI3, nivolumab 1 mg/kg + ipilimumab 3 mg/kg; NIVO3+IPI1, nivolumab 3 mg/kg + ipilimumab 1 mg/kg; TRAE; treatment-related adverse event; TRSAE, treatment-related serious adverse event. aAdverse events were reported during treatment and for ≥100 days following study drug discontinuation and were evaluated according to the CommonTerminology Criteria for Adverse Events v4.0. Adverse events were sorted based on the Medical Dictionary for Regulatory Activities (MedDRA) groupings.