Grades 3 to 5 treatment-emergent adverse events occurring with CLAG-M/sorafenib during the first treatment cycle in phase 1 and at the RP2D
Adverse events based on the organ system class, n (% cycles) . | Phase 1 cohort (n = 46) . | RP2D cohort∗ (n = 41) . |
---|---|---|
Blood and lymphatic system disorders† | ||
Febrile neutropenia | 52 | 40 |
Infections and infestations | ||
Bacteremia | 1 | 1 |
Clostridium difficile | 1 | — |
Enterocolitis/typhlitis | — | 2 |
Lung infection | — | 2 |
Oral infection | 1 | — |
Sepsis | 2† | — |
Sinusitis | 1 | 2‡ |
Skin/soft-tissue infection | 3 | 2 |
Upper respiratory tract infection | 1 | |
Cardiac disorders | ||
Cardiac arrest | — | 1‡ |
Cardiac troponin increase | 1 | |
Cardiomyopathy | — | 2 |
Hypertension | 2 | 2 |
Hypotension | 1 | — |
Pericarditis | 1 | — |
Myocardial infarction | 1 | — |
Ventricular fibrillation | — | 1‡ |
Gastrointestinal disorders | ||
Abdominal pain | — | 1 |
Colon adenocarcinoma | 1 | — |
Dental caries/tooth pain | 1 | 1 |
Diarrhea | 1 | 1 |
Fistula/fissure, anorectal | 1 | 2 |
Rectal pain | — | 1 |
Investigations | ||
aPTT prolonged | 1 | — |
Alanine aminotransferase increased | — | 1 |
Aspartate aminotransferase increased | — | 1 |
Blood bilirubin increased | 1 | 1 |
Metabolism and nutrition disorders | ||
Hyperglycemia | — | 3 |
Hypokalemia | 1 | 2 |
Hyponatremia | 2 | — |
Tumor lysis | 3 | 1 |
Psychiatric disorders | ||
Delirium | 1 | — |
Nervous system disorders | ||
Depressed level of consciousness | 1† | — |
Headache | 1 | — |
Intracranial hemorrhage | 1† | — |
Paresthesia | — | 1 |
Seizure | — | 1 |
Syncope | 1 | 2 |
Renal and urinary disorders | ||
Acute kidney injury | — | 1 |
Hematuria | 1 | — |
Respiratory, thoracic, and mediastinal disorders | ||
Hypoxia | — | 1† |
Pulmonary edema/effusion | — | 2† |
Pulmonary embolism | 2 | |
Skin and subcutaneous tissue disorders | ||
Rash maculo-papular | 17 | 13 |
Pruritis | — | 1 |
Other | ||
Eye disorders: blurred vision | 1 | — |
Ear and labyrinth disorders: Bell palsy | 1 | — |
Infusion reaction, blood product | — | 2 |
Musculoskeletal: joint or extremity pain | 2 | — |
Vascular: catheter-associated thrombosis | 4 | 3 |
Adverse events based on the organ system class, n (% cycles) . | Phase 1 cohort (n = 46) . | RP2D cohort∗ (n = 41) . |
---|---|---|
Blood and lymphatic system disorders† | ||
Febrile neutropenia | 52 | 40 |
Infections and infestations | ||
Bacteremia | 1 | 1 |
Clostridium difficile | 1 | — |
Enterocolitis/typhlitis | — | 2 |
Lung infection | — | 2 |
Oral infection | 1 | — |
Sepsis | 2† | — |
Sinusitis | 1 | 2‡ |
Skin/soft-tissue infection | 3 | 2 |
Upper respiratory tract infection | 1 | |
Cardiac disorders | ||
Cardiac arrest | — | 1‡ |
Cardiac troponin increase | 1 | |
Cardiomyopathy | — | 2 |
Hypertension | 2 | 2 |
Hypotension | 1 | — |
Pericarditis | 1 | — |
Myocardial infarction | 1 | — |
Ventricular fibrillation | — | 1‡ |
Gastrointestinal disorders | ||
Abdominal pain | — | 1 |
Colon adenocarcinoma | 1 | — |
Dental caries/tooth pain | 1 | 1 |
Diarrhea | 1 | 1 |
Fistula/fissure, anorectal | 1 | 2 |
Rectal pain | — | 1 |
Investigations | ||
aPTT prolonged | 1 | — |
Alanine aminotransferase increased | — | 1 |
Aspartate aminotransferase increased | — | 1 |
Blood bilirubin increased | 1 | 1 |
Metabolism and nutrition disorders | ||
Hyperglycemia | — | 3 |
Hypokalemia | 1 | 2 |
Hyponatremia | 2 | — |
Tumor lysis | 3 | 1 |
Psychiatric disorders | ||
Delirium | 1 | — |
Nervous system disorders | ||
Depressed level of consciousness | 1† | — |
Headache | 1 | — |
Intracranial hemorrhage | 1† | — |
Paresthesia | — | 1 |
Seizure | — | 1 |
Syncope | 1 | 2 |
Renal and urinary disorders | ||
Acute kidney injury | — | 1 |
Hematuria | 1 | — |
Respiratory, thoracic, and mediastinal disorders | ||
Hypoxia | — | 1† |
Pulmonary edema/effusion | — | 2† |
Pulmonary embolism | 2 | |
Skin and subcutaneous tissue disorders | ||
Rash maculo-papular | 17 | 13 |
Pruritis | — | 1 |
Other | ||
Eye disorders: blurred vision | 1 | — |
Ear and labyrinth disorders: Bell palsy | 1 | — |
Infusion reaction, blood product | — | 2 |
Musculoskeletal: joint or extremity pain | 2 | — |
Vascular: catheter-associated thrombosis | 4 | 3 |
Hematologic treatment-emergent adverse events were not collected, except for febrile neutropenia and bleeding events ≥grade 3.
Six patients are represented in both the phase 1 and RP2D cohorts.
One of the events is a grade 4 event.
One of the events is a grade 5 event: 1 each for the adverse events marked.