Study: NCT04382066

Adverse event: Anaphylactic reaction
Serious: yes
Organ System: Immune system disorders
Notes: Anaphylactic reaction Grade 3 in Arm A (1.5 mg plitidepsin) attributed to plitidepsin.
Frequency: 1 affected / 15 at risk

Adverse event: Acute respiratory distress syndrome
Serious: yes
Organ System: Respiratory, thoracic and mediastinal disorders
Notes: 1 Acute respiratory distress syndrome grade 3 and 1 grade 4 and 1 grade 5 in the same patient in Arm A (1.5 mg plitidepsin), 1 grade 4 in Arm B (2 mg plitidepsin) and 1 grade 4 in Arm C (2.5 mg plitidepsin).
Frequency: 2 affected / 15 at risk

Adverse event: Condition aggravated
Serious: yes
Organ System: General disorders
Notes: Condition aggravated grade 3 in Arm A (1.5 mg plitidepsin)
Frequency: 1 affected / 15 at risk

Adverse event: Pyelonephritis
Serious: yes
Organ System: Infections and infestations
Frequency: 1 affected / 15 at risk

Adverse event: COVID-19 pneumonia
Serious: yes
Organ System: Infections and infestations
Notes: 1 COVID-19 pneumonia grade 3 in Arm A (1.5 mg ) and 1 grade 3 and 1 grade 5 in the same patient in Arm C (2.5 mg plitidepsin).
Frequency: 1 affected / 15 at risk

Adverse event: Lymphopenia
Serious: no
Organ System: Blood and lymphatic system disorders
Frequency: 1 affected / 15 at risk

Adverse event: Abdominal pain
Serious: no
Organ System: Gastrointestinal disorders
Frequency: 2 affected / 15 at risk

Adverse event: Constipation
Serious: no
Organ System: Gastrointestinal disorders
Frequency: 4 affected / 15 at risk

Adverse event: Diarrhoea
Serious: no
Organ System: Gastrointestinal disorders
Notes: 1 diarrhoea grade 3 in Arm A (1.5 mg plitidepsin) was attributed to plitidepsin.
Frequency: 1 affected / 15 at risk

Adverse event: Dyspepsia
Serious: no
Organ System: Gastrointestinal disorders
Frequency: 2 affected / 15 at risk

Adverse event: Nausea
Serious: no
Organ System: Gastrointestinal disorders
Frequency: 6 affected / 15 at risk

Adverse event: COVID-19 pneumonia
Serious: no
Organ System: Infections and infestations
Frequency: 2 affected / 15 at risk

Adverse event: Pneumonia
Serious: no
Organ System: Infections and infestations
Notes: 1 Pneumonia grade 3 in Arm A (1.5 mg plitidepsin).
Frequency: 1 affected / 15 at risk

Adverse event: Skin candida
Serious: no
Organ System: Infections and infestations
Frequency: 1 affected / 15 at risk

Adverse event: Blood alkaline phosphatase increased
Serious: no
Organ System: Investigations
Frequency: 1 affected / 15 at risk

Adverse event: Alanine aminotransferase increased
Serious: no
Organ System: Investigations
Notes: 1 ALT increased grade 3 in Arm B (2 mg plitidepsin).
Frequency: 2 affected / 15 at risk

Adverse event: Aspartate aminotransferase increased
Serious: no
Organ System: Investigations
Frequency: 1 affected / 15 at risk

Adverse event: C-reactive protein increased
Serious: no
Organ System: Investigations
Notes: 1 C-reactive protein increased grade 3 in Arm A (1.5 mg plitidepsin).
Frequency: 4 affected / 15 at risk

Adverse event: Serum ferritin increased
Serious: no
Organ System: Investigations
Notes: 1 Ferritin increased grade 3 in Arm A (1.5 mg plitidepsin).
Frequency: 5 affected / 15 at risk

Adverse event: Gamma-glutamyltransferase increased
Serious: no
Organ System: Investigations
Notes: 1 GGT increased grade 3 in Arm A (1.5 mg plitidepsin) and 2 grade 3 in Arm B (2 mg plitidepsin)
Frequency: 3 affected / 15 at risk

Adverse event: Blood lactate dehydrogenase increased
Serious: no
Organ System: Investigations
Frequency: 1 affected / 15 at risk

Adverse event: Low density lipoprotein increased
Serious: no
Organ System: Investigations
Frequency: 1 affected / 15 at risk

Adverse event: Oxygen saturation decreased
Serious: no
Organ System: Investigations
Frequency: 1 affected / 15 at risk

Adverse event: Transaminases increased
Serious: no
Organ System: Investigations
Frequency: 1 affected / 15 at risk

Adverse event: Triglycerides increased
Serious: no
Organ System: Investigations
Frequency: 1 affected / 15 at risk

Adverse event: Fibrin D dimer increased
Serious: no
Organ System: Investigations
Frequency: 3 affected / 15 at risk

Adverse event: Decreased appetite
Serious: no
Organ System: Metabolism and nutrition disorders
Frequency: 1 affected / 15 at risk

Adverse event: Dehydration
Serious: no
Organ System: Metabolism and nutrition disorders
Frequency: 1 affected / 15 at risk

Adverse event: Hyponatraemia
Serious: no
Organ System: Metabolism and nutrition disorders
Frequency: 1 affected / 15 at risk

Adverse event: Hyperglycaemia
Serious: no
Organ System: Metabolism and nutrition disorders
Frequency: 3 affected / 15 at risk

Adverse event: Arthralgia
Serious: no
Organ System: Musculoskeletal and connective tissue disorders
Frequency: 1 affected / 15 at risk

Adverse event: Muscular weakness
Serious: no
Organ System: Musculoskeletal and connective tissue disorders
Frequency: 1 affected / 15 at risk

Adverse event: Dizziness
Serious: no
Organ System: Nervous system disorders
Frequency: 1 affected / 15 at risk

Adverse event: Headache
Serious: no
Organ System: Nervous system disorders
Frequency: 4 affected / 15 at risk

Adverse event: Insomnia
Serious: no
Organ System: Nervous system disorders
Frequency: 2 affected / 15 at risk

Adverse event: Paraesthesia
Serious: no
Organ System: Nervous system disorders
Frequency: 1 affected / 15 at risk

Adverse event: Presyncope
Serious: no
Organ System: Nervous system disorders
Frequency: 3 affected / 15 at risk

Adverse event: Anxiety
Serious: no
Organ System: Psychiatric disorders
Frequency: 1 affected / 15 at risk

Adverse event: Pollakiuria
Serious: no
Organ System: Renal and urinary disorders
Frequency: 1 affected / 15 at risk

Adverse event: Prerenal failure
Serious: no
Organ System: Renal and urinary disorders
Frequency: 1 affected / 15 at risk

Adverse event: Respiratory failure
Serious: no
Organ System: Respiratory, thoracic and mediastinal disorders
Frequency: 1 affected / 15 at risk

Adverse event: Cough
Serious: no
Organ System: Respiratory, thoracic and mediastinal disorders
Frequency: 4 affected / 15 at risk

Adverse event: Dyspnoea
Serious: no
Organ System: Respiratory, thoracic and mediastinal disorders
Frequency: 3 affected / 15 at risk

Adverse event: Tachypnoea
Serious: no
Organ System: Respiratory, thoracic and mediastinal disorders
Frequency: 1 affected / 15 at risk

Adverse event: Phlebitis
Serious: no
Organ System: Vascular disorders
Frequency: 3 affected / 15 at risk

Adverse event: Thrombophlebitis
Serious: no
Organ System: Vascular disorders
Frequency: 1 affected / 15 at risk

Adverse event: Asthenia
Serious: no
Organ System: General disorders
Frequency: 3 affected / 15 at risk

Adverse event: Pyrexia
Serious: no
Organ System: General disorders
Frequency: 8 affected / 15 at risk

Adverse event: Malaise
Serious: no
Organ System: General disorders
Frequency: 1 affected / 15 at risk

Adverse event: Interstitial lung disease
Serious: no
Organ System: Respiratory, thoracic and mediastinal disorders
Frequency: 1 affected / 15 at risk

Adverse event: Pleuritic pain
Serious: no
Organ System: Respiratory, thoracic and mediastinal disorders
Frequency: 1 affected / 15 at risk

Adverse event: Pneumothorax spontaneous
Serious: no
Organ System: Respiratory, thoracic and mediastinal disorders
Frequency: 1 affected / 15 at risk

Adverse event: Tenosynovitis
Serious: no
Organ System: Musculoskeletal and connective tissue disorders
Frequency: 1 affected / 15 at risk

Adverse event: Acute respiratory distress syndrome
Serious: yes
Organ System: Respiratory, thoracic and mediastinal disorders
Notes: 1 Acute respiratory distress syndrome grade 3 and 1 grade 4 and 1 grade 5 in the same patient in Arm A (1.5 mg plitidepsin), 1 grade 4 in Arm B (2 mg plitidepsin) and 1 grade 4 in Arm C (2.5 mg plitidepsin).
Frequency: 1 affected / 15 at risk

Adverse event: Lymphopenia
Serious: no
Organ System: Blood and lymphatic system disorders
Frequency: 1 affected / 15 at risk

Adverse event: Vertigo
Serious: no
Organ System: Ear and labyrinth disorders
Frequency: 1 affected / 15 at risk

Adverse event: Constipation
Serious: no
Organ System: Gastrointestinal disorders
Frequency: 2 affected / 15 at risk

Adverse event: Diarrhoea
Serious: no
Organ System: Gastrointestinal disorders
Notes: 1 diarrhoea grade 3 in Arm A (1.5 mg plitidepsin) was attributed to plitidepsin.
Frequency: 4 affected / 15 at risk

Adverse event: Dyspepsia
Serious: no
Organ System: Gastrointestinal disorders
Frequency: 1 affected / 15 at risk

Adverse event: Nausea
Serious: no
Organ System: Gastrointestinal disorders
Frequency: 6 affected / 15 at risk

Adverse event: Vomiting
Serious: no
Organ System: Gastrointestinal disorders
Frequency: 4 affected / 15 at risk

Adverse event: Bacteraemia
Serious: no
Organ System: Infections and infestations
Notes: 1 Bacteremia grade 3 in Arm C (2.5 mg plitidepsin).
Frequency: 1 affected / 15 at risk

Adverse event: Pneumonia
Serious: no
Organ System: Infections and infestations
Notes: 1 Pneumonia grade 3 in Arm A (1.5 mg plitidepsin).
Frequency: 1 affected / 15 at risk

Adverse event: Viral infection
Serious: no
Organ System: Infections and infestations
Frequency: 1 affected / 15 at risk

Adverse event: Fall
Serious: no
Organ System: Injury, poisoning and procedural complications
Frequency: 1 affected / 15 at risk

Adverse event: Blood alkaline phosphatase increased
Serious: no
Organ System: Investigations
Frequency: 1 affected / 15 at risk

Adverse event: Alanine aminotransferase increased
Serious: no
Organ System: Investigations
Notes: 1 ALT increased grade 3 in Arm B (2 mg plitidepsin).
Frequency: 1 affected / 15 at risk

Adverse event: Aspartate aminotransferase increased
Serious: no
Organ System: Investigations
Frequency: 1 affected / 15 at risk

Adverse event: Blood cholesterol increased
Serious: no
Organ System: Investigations
Frequency: 1 affected / 15 at risk

Adverse event: Blood creatinine increased
Serious: no
Organ System: Investigations
Frequency: 1 affected / 15 at risk

Adverse event: Blood glucose increased
Serious: no
Organ System: Investigations
Frequency: 1 affected / 15 at risk

Adverse event: Blood creatine phosphokinase increased
Serious: no
Organ System: Investigations
Frequency: 2 affected / 15 at risk

Adverse event: C-reactive protein increased
Serious: no
Organ System: Investigations
Notes: 1 C-reactive protein increased grade 3 in Arm A (1.5 mg plitidepsin).
Frequency: 4 affected / 15 at risk

Adverse event: Serum ferritin increased
Serious: no
Organ System: Investigations
Notes: 1 Ferritin increased grade 3 in Arm A (1.5 mg plitidepsin).
Frequency: 4 affected / 15 at risk

Adverse event: Gamma-glutamyltransferase increased
Serious: no
Organ System: Investigations
Notes: 1 GGT increased grade 3 in Arm A (1.5 mg plitidepsin) and 2 grade 3 in Arm B (2 mg plitidepsin)
Frequency: 2 affected / 15 at risk

Adverse event: Blood lactate dehydrogenase increased
Serious: no
Organ System: Investigations
Frequency: 1 affected / 15 at risk

Adverse event: Triglycerides increased
Serious: no
Organ System: Investigations
Frequency: 1 affected / 15 at risk

Adverse event: Fibrin D dimer increased
Serious: no
Organ System: Investigations
Frequency: 2 affected / 15 at risk

Adverse event: Decreased appetite
Serious: no
Organ System: Metabolism and nutrition disorders
Frequency: 1 affected / 15 at risk

Adverse event: Hyperglycaemia
Serious: no
Organ System: Metabolism and nutrition disorders
Frequency: 2 affected / 15 at risk

Adverse event: Back pain
Serious: no
Organ System: Musculoskeletal and connective tissue disorders
Frequency: 1 affected / 15 at risk

Adverse event: Myalgia
Serious: no
Organ System: Musculoskeletal and connective tissue disorders
Frequency: 1 affected / 15 at risk

Adverse event: Headache
Serious: no
Organ System: Nervous system disorders
Frequency: 2 affected / 15 at risk

Adverse event: Insomnia
Serious: no
Organ System: Nervous system disorders
Frequency: 2 affected / 15 at risk

Adverse event: Migraine
Serious: no
Organ System: Nervous system disorders
Frequency: 1 affected / 15 at risk

Adverse event: Presyncope
Serious: no
Organ System: Nervous system disorders
Frequency: 1 affected / 15 at risk

Adverse event: Somnolence
Serious: no
Organ System: Nervous system disorders
Frequency: 1 affected / 15 at risk

Adverse event: Agitation
Serious: no
Organ System: Psychiatric disorders
Frequency: 1 affected / 15 at risk

Adverse event: Delirium
Serious: no
Organ System: Psychiatric disorders
Frequency: 1 affected / 15 at risk

Adverse event: Breast engorgement
Serious: no
Organ System: Reproductive system and breast disorders
Frequency: 1 affected / 15 at risk

Adverse event: Cough
Serious: no
Organ System: Respiratory, thoracic and mediastinal disorders
Frequency: 3 affected / 15 at risk

Adverse event: Dyspnoea
Serious: no
Organ System: Respiratory, thoracic and mediastinal disorders
Frequency: 2 affected / 15 at risk

Adverse event: Hypoxia
Serious: no
Organ System: Respiratory, thoracic and mediastinal disorders
Frequency: 1 affected / 15 at risk

Adverse event: Tachypnoea
Serious: no
Organ System: Respiratory, thoracic and mediastinal disorders
Frequency: 1 affected / 15 at risk

Adverse event: Skin ulcer
Serious: no
Organ System: Skin and subcutaneous tissue disorders
Frequency: 1 affected / 15 at risk

Adverse event: Phlebitis
Serious: no
Organ System: Vascular disorders
Frequency: 3 affected / 15 at risk

Adverse event: Asthenia
Serious: no
Organ System: General disorders
Frequency: 1 affected / 15 at risk

Adverse event: Chest discomfort
Serious: no
Organ System: General disorders
Frequency: 1 affected / 15 at risk

Adverse event: Pyrexia
Serious: no
Organ System: General disorders
Frequency: 5 affected / 15 at risk

Adverse event: Fatigue
Serious: no
Organ System: General disorders
Frequency: 1 affected / 15 at risk

Adverse event: Platelet count decreased
Serious: no
Organ System: Investigations
Frequency: 1 affected / 15 at risk

Adverse event: Acute respiratory distress syndrome
Serious: yes
Organ System: Respiratory, thoracic and mediastinal disorders
Notes: 1 Acute respiratory distress syndrome grade 3 and 1 grade 4 and 1 grade 5 in the same patient in Arm A (1.5 mg plitidepsin), 1 grade 4 in Arm B (2 mg plitidepsin) and 1 grade 4 in Arm C (2.5 mg plitidepsin).
Frequency: 1 affected / 15 at risk

Adverse event: Respiratory failure
Serious: yes
Organ System: Respiratory, thoracic and mediastinal disorders
Notes: Acute respiratory failure grade 5 in Arm C (2.5 mg plitidepsin)
Frequency: 1 affected / 15 at risk

Adverse event: Status epilepticus
Serious: yes
Organ System: Nervous system disorders
Notes: Status epilepticus grade 3 in Arm C (2.5 mg plitidepsin)
Frequency: 1 affected / 15 at risk

Adverse event: Pneumomediastinum
Serious: yes
Organ System: Respiratory, thoracic and mediastinal disorders
Frequency: 1 affected / 15 at risk

Adverse event: COVID-19 pneumonia
Serious: yes
Organ System: Infections and infestations
Notes: 1 COVID-19 pneumonia grade 3 in Arm A (1.5 mg ) and 1 grade 3 and 1 grade 5 in the same patient in Arm C (2.5 mg plitidepsin).
Frequency: 1 affected / 15 at risk

Adverse event: Superinfection bacterial
Serious: yes
Organ System: Infections and infestations
Frequency: 1 affected / 15 at risk

Adverse event: Anaemia
Serious: no
Organ System: Blood and lymphatic system disorders
Frequency: 1 affected / 15 at risk

Adverse event: Leukocytosis
Serious: no
Organ System: Blood and lymphatic system disorders
Notes: 1 Leukocytosis grade 3 in Arm C (2.5 mg plitidepsin).
Frequency: 3 affected / 15 at risk

Adverse event: Lymphopenia
Serious: no
Organ System: Blood and lymphatic system disorders
Frequency: 1 affected / 15 at risk

Adverse event: Neutrophilia
Serious: no
Organ System: Blood and lymphatic system disorders
Frequency: 1 affected / 15 at risk

Adverse event: Atrial fibrillation
Serious: no
Organ System: Cardiac disorders
Frequency: 1 affected / 15 at risk

Adverse event: Tachycardia
Serious: no
Organ System: Cardiac disorders
Frequency: 1 affected / 15 at risk

Adverse event: Abdominal pain
Serious: no
Organ System: Gastrointestinal disorders
Frequency: 2 affected / 15 at risk

Adverse event: Constipation
Serious: no
Organ System: Gastrointestinal disorders
Frequency: 2 affected / 15 at risk

Adverse event: Diarrhoea
Serious: no
Organ System: Gastrointestinal disorders
Notes: 1 diarrhoea grade 3 in Arm A (1.5 mg plitidepsin) was attributed to plitidepsin.
Frequency: 3 affected / 15 at risk

Adverse event: Dyspepsia
Serious: no
Organ System: Gastrointestinal disorders
Frequency: 1 affected / 15 at risk

Adverse event: Nausea
Serious: no
Organ System: Gastrointestinal disorders
Frequency: 7 affected / 15 at risk

Adverse event: Rectal haemorrhage
Serious: no
Organ System: Gastrointestinal disorders
Frequency: 1 affected / 15 at risk

Adverse event: Vomiting
Serious: no
Organ System: Gastrointestinal disorders
Frequency: 4 affected / 15 at risk

Adverse event: Hypoalbuminaemia
Serious: no
Organ System: Hepatobiliary disorders
Frequency: 1 affected / 15 at risk

Adverse event: Bacteraemia
Serious: no
Organ System: Infections and infestations
Notes: 1 Bacteremia grade 3 in Arm C (2.5 mg plitidepsin).
Frequency: 1 affected / 15 at risk

Adverse event: Urinary tract infection
Serious: no
Organ System: Infections and infestations
Notes: 1 Urinary tract infection grade 3 in Arm C (2.5 mg plitidepsin).
Frequency: 2 affected / 15 at risk

Adverse event: Alanine aminotransferase increased
Serious: no
Organ System: Investigations
Notes: 1 ALT increased grade 3 in Arm B (2 mg plitidepsin).
Frequency: 2 affected / 15 at risk

Adverse event: Amylase increased
Serious: no
Organ System: Investigations
Frequency: 1 affected / 15 at risk

Adverse event: Aspartate aminotransferase increased
Serious: no
Organ System: Investigations
Frequency: 1 affected / 15 at risk

Adverse event: Blood fibrinogen increased
Serious: no
Organ System: Investigations
Frequency: 1 affected / 15 at risk

Adverse event: C-reactive protein increased
Serious: no
Organ System: Investigations
Notes: 1 C-reactive protein increased grade 3 in Arm A (1.5 mg plitidepsin).
Frequency: 3 affected / 15 at risk

Adverse event: Serum ferritin increased
Serious: no
Organ System: Investigations
Notes: 1 Ferritin increased grade 3 in Arm A (1.5 mg plitidepsin).
Frequency: 5 affected / 15 at risk

Adverse event: Gamma-glutamyltransferase increased
Serious: no
Organ System: Investigations
Notes: 1 GGT increased grade 3 in Arm A (1.5 mg plitidepsin) and 2 grade 3 in Arm B (2 mg plitidepsin)
Frequency: 1 affected / 15 at risk

Adverse event: Blood lactate dehydrogenase increased
Serious: no
Organ System: Investigations
Frequency: 2 affected / 15 at risk

Adverse event: Fibrin D dimer increased
Serious: no
Organ System: Investigations
Frequency: 3 affected / 15 at risk

Adverse event: Hyperglycaemia
Serious: no
Organ System: Metabolism and nutrition disorders
Frequency: 3 affected / 15 at risk

Adverse event: Hyperkalaemia
Serious: no
Organ System: Metabolism and nutrition disorders
Frequency: 1 affected / 15 at risk

Adverse event: Malnutrition
Serious: no
Organ System: Metabolism and nutrition disorders
Frequency: 1 affected / 15 at risk

Adverse event: Back pain
Serious: no
Organ System: Musculoskeletal and connective tissue disorders
Frequency: 1 affected / 15 at risk

Adverse event: Dizziness
Serious: no
Organ System: Nervous system disorders
Frequency: 2 affected / 15 at risk

Adverse event: Dysgeusia
Serious: no
Organ System: Nervous system disorders
Frequency: 2 affected / 15 at risk

Adverse event: Somnolence
Serious: no
Organ System: Nervous system disorders
Frequency: 1 affected / 15 at risk

Adverse event: Delirium
Serious: no
Organ System: Psychiatric disorders
Frequency: 1 affected / 15 at risk

Adverse event: Prerenal failure
Serious: no
Organ System: Renal and urinary disorders
Frequency: 1 affected / 15 at risk

Adverse event: Renal impairment
Serious: no
Organ System: Renal and urinary disorders
Notes: 1 Renal impairment grade 3 in Arm A (1.5 mg plitidepsin).
Frequency: 2 affected / 15 at risk

Adverse event: Respiratory failure
Serious: no
Organ System: Respiratory, thoracic and mediastinal disorders
Frequency: 1 affected / 15 at risk

Adverse event: Chest discomfort
Serious: no
Organ System: Respiratory, thoracic and mediastinal disorders
Frequency: 1 affected / 15 at risk

Adverse event: Cough
Serious: no
Organ System: Respiratory, thoracic and mediastinal disorders
Frequency: 4 affected / 15 at risk

Adverse event: Dyspnoea
Serious: no
Organ System: Respiratory, thoracic and mediastinal disorders
Frequency: 2 affected / 15 at risk

Adverse event: Hypoxia
Serious: no
Organ System: Respiratory, thoracic and mediastinal disorders
Frequency: 1 affected / 15 at risk

Adverse event: Productive cough
Serious: no
Organ System: Respiratory, thoracic and mediastinal disorders
Frequency: 1 affected / 15 at risk

Adverse event: Respiratory distress
Serious: no
Organ System: Respiratory, thoracic and mediastinal disorders
Frequency: 1 affected / 15 at risk

Adverse event: Hypertension
Serious: no
Organ System: Vascular disorders
Frequency: 2 affected / 15 at risk

Adverse event: Hypotension
Serious: no
Organ System: Vascular disorders
Frequency: 1 affected / 15 at risk

Adverse event: Phlebitis
Serious: no
Organ System: Vascular disorders
Frequency: 2 affected / 15 at risk

Adverse event: Asthenia
Serious: no
Organ System: General disorders
Frequency: 2 affected / 15 at risk

Adverse event: Pyrexia
Serious: no
Organ System: General disorders
Frequency: 7 affected / 15 at risk

Adverse event: Temperature regulation disorder
Serious: no
Organ System: General disorders
Frequency: 1 affected / 15 at risk

Adverse event: Neutrophil count increased
Serious: no
Organ System: Investigations
Frequency: 1 affected / 15 at risk

Adverse event: Interleukin level increased
Serious: no
Organ System: Investigations
Frequency: 1 affected / 15 at risk

Adverse event: Lipase increased
Serious: no
Organ System: Investigations
Frequency: 1 affected / 15 at risk

Adverse event: Anaphylactic reaction
Serious: yes
Organ System: Immune system disorders
Notes: Anaphylactic reaction Grade 3 in Arm A (1.5 mg plitidepsin) attributed to plitidepsin.
Frequency: 1 affected / 45 at risk

Adverse event: Acute respiratory distress syndrome
Serious: yes
Organ System: Respiratory, thoracic and mediastinal disorders
Notes: 1 Acute respiratory distress syndrome grade 3 and 1 grade 4 and 1 grade 5 in the same patient in Arm A (1.5 mg plitidepsin), 1 grade 4 in Arm B (2 mg plitidepsin) and 1 grade 4 in Arm C (2.5 mg plitidepsin).
Frequency: 4 affected / 45 at risk

Adverse event: Respiratory failure
Serious: yes
Organ System: Respiratory, thoracic and mediastinal disorders
Notes: Acute respiratory failure grade 5 in Arm C (2.5 mg plitidepsin)
Frequency: 1 affected / 45 at risk

Adverse event: Status epilepticus
Serious: yes
Organ System: Nervous system disorders
Notes: Status epilepticus grade 3 in Arm C (2.5 mg plitidepsin)
Frequency: 1 affected / 45 at risk

Adverse event: Pneumomediastinum
Serious: yes
Organ System: Respiratory, thoracic and mediastinal disorders
Frequency: 1 affected / 45 at risk

Adverse event: Condition aggravated
Serious: yes
Organ System: General disorders
Notes: Condition aggravated grade 3 in Arm A (1.5 mg plitidepsin)
Frequency: 1 affected / 45 at risk

Adverse event: Pyelonephritis
Serious: yes
Organ System: Infections and infestations
Frequency: 1 affected / 45 at risk

Adverse event: COVID-19 pneumonia
Serious: yes
Organ System: Infections and infestations
Notes: 1 COVID-19 pneumonia grade 3 in Arm A (1.5 mg ) and 1 grade 3 and 1 grade 5 in the same patient in Arm C (2.5 mg plitidepsin).
Frequency: 2 affected / 45 at risk

Adverse event: Superinfection bacterial
Serious: yes
Organ System: Infections and infestations
Frequency: 1 affected / 45 at risk

Adverse event: Anaemia
Serious: no
Organ System: Blood and lymphatic system disorders
Frequency: 1 affected / 45 at risk

Adverse event: Leukocytosis
Serious: no
Organ System: Blood and lymphatic system disorders
Notes: 1 Leukocytosis grade 3 in Arm C (2.5 mg plitidepsin).
Frequency: 3 affected / 45 at risk

Adverse event: Lymphopenia
Serious: no
Organ System: Blood and lymphatic system disorders
Frequency: 3 affected / 45 at risk

Adverse event: Neutrophilia
Serious: no
Organ System: Blood and lymphatic system disorders
Frequency: 1 affected / 45 at risk

Adverse event: Atrial fibrillation
Serious: no
Organ System: Cardiac disorders
Frequency: 1 affected / 45 at risk

Adverse event: Tachycardia
Serious: no
Organ System: Cardiac disorders
Frequency: 1 affected / 45 at risk

Adverse event: Vertigo
Serious: no
Organ System: Ear and labyrinth disorders
Frequency: 1 affected / 45 at risk

Adverse event: Abdominal pain
Serious: no
Organ System: Gastrointestinal disorders
Frequency: 4 affected / 45 at risk

Adverse event: Constipation
Serious: no
Organ System: Gastrointestinal disorders
Frequency: 8 affected / 45 at risk

Adverse event: Diarrhoea
Serious: no
Organ System: Gastrointestinal disorders
Notes: 1 diarrhoea grade 3 in Arm A (1.5 mg plitidepsin) was attributed to plitidepsin.
Frequency: 8 affected / 45 at risk

Adverse event: Dyspepsia
Serious: no
Organ System: Gastrointestinal disorders
Frequency: 4 affected / 45 at risk

Adverse event: Nausea
Serious: no
Organ System: Gastrointestinal disorders
Frequency: 19 affected / 45 at risk

Adverse event: Rectal haemorrhage
Serious: no
Organ System: Gastrointestinal disorders
Frequency: 1 affected / 45 at risk

Adverse event: Vomiting
Serious: no
Organ System: Gastrointestinal disorders
Frequency: 8 affected / 45 at risk

Adverse event: Hypoalbuminaemia
Serious: no
Organ System: Hepatobiliary disorders
Frequency: 1 affected / 45 at risk

Adverse event: Bacteraemia
Serious: no
Organ System: Infections and infestations
Notes: 1 Bacteremia grade 3 in Arm C (2.5 mg plitidepsin).
Frequency: 2 affected / 45 at risk

Adverse event: COVID-19 pneumonia
Serious: no
Organ System: Infections and infestations
Frequency: 2 affected / 45 at risk

Adverse event: Pneumonia
Serious: no
Organ System: Infections and infestations
Notes: 1 Pneumonia grade 3 in Arm A (1.5 mg plitidepsin).
Frequency: 2 affected / 45 at risk

Adverse event: Skin candida
Serious: no
Organ System: Infections and infestations
Frequency: 1 affected / 45 at risk

Adverse event: Urinary tract infection
Serious: no
Organ System: Infections and infestations
Notes: 1 Urinary tract infection grade 3 in Arm C (2.5 mg plitidepsin).
Frequency: 2 affected / 45 at risk

Adverse event: Viral infection
Serious: no
Organ System: Infections and infestations
Frequency: 1 affected / 45 at risk

Adverse event: Fall
Serious: no
Organ System: Injury, poisoning and procedural complications
Frequency: 1 affected / 45 at risk

Adverse event: Blood alkaline phosphatase increased
Serious: no
Organ System: Investigations
Frequency: 2 affected / 45 at risk

Adverse event: Alanine aminotransferase increased
Serious: no
Organ System: Investigations
Notes: 1 ALT increased grade 3 in Arm B (2 mg plitidepsin).
Frequency: 5 affected / 45 at risk

Adverse event: Amylase increased
Serious: no
Organ System: Investigations
Frequency: 1 affected / 45 at risk

Adverse event: Aspartate aminotransferase increased
Serious: no
Organ System: Investigations
Frequency: 3 affected / 45 at risk

Adverse event: Blood cholesterol increased
Serious: no
Organ System: Investigations
Frequency: 1 affected / 45 at risk

Adverse event: Blood creatinine increased
Serious: no
Organ System: Investigations
Frequency: 1 affected / 45 at risk

Adverse event: Blood fibrinogen increased
Serious: no
Organ System: Investigations
Frequency: 1 affected / 45 at risk

Adverse event: Blood glucose increased
Serious: no
Organ System: Investigations
Frequency: 1 affected / 45 at risk

Adverse event: Blood creatine phosphokinase increased
Serious: no
Organ System: Investigations
Frequency: 2 affected / 45 at risk

Adverse event: C-reactive protein increased
Serious: no
Organ System: Investigations
Notes: 1 C-reactive protein increased grade 3 in Arm A (1.5 mg plitidepsin).
Frequency: 11 affected / 45 at risk

Adverse event: Serum ferritin increased
Serious: no
Organ System: Investigations
Notes: 1 Ferritin increased grade 3 in Arm A (1.5 mg plitidepsin).
Frequency: 14 affected / 45 at risk

Adverse event: Gamma-glutamyltransferase increased
Serious: no
Organ System: Investigations
Notes: 1 GGT increased grade 3 in Arm A (1.5 mg plitidepsin) and 2 grade 3 in Arm B (2 mg plitidepsin)
Frequency: 6 affected / 45 at risk

Adverse event: Blood lactate dehydrogenase increased
Serious: no
Organ System: Investigations
Frequency: 4 affected / 45 at risk

Adverse event: Low density lipoprotein increased
Serious: no
Organ System: Investigations
Frequency: 1 affected / 45 at risk

Adverse event: Oxygen saturation decreased
Serious: no
Organ System: Investigations
Frequency: 1 affected / 45 at risk

Adverse event: Transaminases increased
Serious: no
Organ System: Investigations
Frequency: 1 affected / 45 at risk

Adverse event: Triglycerides increased
Serious: no
Organ System: Investigations
Frequency: 2 affected / 45 at risk

Adverse event: Fibrin D dimer increased
Serious: no
Organ System: Investigations
Frequency: 8 affected / 45 at risk

Adverse event: Decreased appetite
Serious: no
Organ System: Metabolism and nutrition disorders
Frequency: 2 affected / 45 at risk

Adverse event: Dehydration
Serious: no
Organ System: Metabolism and nutrition disorders
Frequency: 1 affected / 45 at risk

Adverse event: Hyponatraemia
Serious: no
Organ System: Metabolism and nutrition disorders
Frequency: 1 affected / 45 at risk

Adverse event: Hyperglycaemia
Serious: no
Organ System: Metabolism and nutrition disorders
Frequency: 8 affected / 45 at risk

Adverse event: Hyperkalaemia
Serious: no
Organ System: Metabolism and nutrition disorders
Frequency: 1 affected / 45 at risk

Adverse event: Malnutrition
Serious: no
Organ System: Metabolism and nutrition disorders
Frequency: 1 affected / 45 at risk

Adverse event: Arthralgia
Serious: no
Organ System: Musculoskeletal and connective tissue disorders
Frequency: 1 affected / 45 at risk

Adverse event: Back pain
Serious: no
Organ System: Musculoskeletal and connective tissue disorders
Frequency: 2 affected / 45 at risk

Adverse event: Muscular weakness
Serious: no
Organ System: Musculoskeletal and connective tissue disorders
Frequency: 1 affected / 45 at risk

Adverse event: Myalgia
Serious: no
Organ System: Musculoskeletal and connective tissue disorders
Frequency: 1 affected / 45 at risk

Adverse event: Dizziness
Serious: no
Organ System: Nervous system disorders
Frequency: 3 affected / 45 at risk

Adverse event: Dysgeusia
Serious: no
Organ System: Nervous system disorders
Frequency: 2 affected / 45 at risk

Adverse event: Headache
Serious: no
Organ System: Nervous system disorders
Frequency: 6 affected / 45 at risk

Adverse event: Insomnia
Serious: no
Organ System: Nervous system disorders
Frequency: 4 affected / 45 at risk

Adverse event: Migraine
Serious: no
Organ System: Nervous system disorders
Frequency: 1 affected / 45 at risk

Adverse event: Paraesthesia
Serious: no
Organ System: Nervous system disorders
Frequency: 1 affected / 45 at risk

Adverse event: Presyncope
Serious: no
Organ System: Nervous system disorders
Frequency: 4 affected / 45 at risk

Adverse event: Somnolence
Serious: no
Organ System: Nervous system disorders
Frequency: 2 affected / 45 at risk

Adverse event: Agitation
Serious: no
Organ System: Psychiatric disorders
Frequency: 1 affected / 45 at risk

Adverse event: Anxiety
Serious: no
Organ System: Psychiatric disorders
Frequency: 1 affected / 45 at risk

Adverse event: Delirium
Serious: no
Organ System: Psychiatric disorders
Frequency: 2 affected / 45 at risk

Adverse event: Pollakiuria
Serious: no
Organ System: Renal and urinary disorders
Frequency: 1 affected / 45 at risk

Adverse event: Prerenal failure
Serious: no
Organ System: Renal and urinary disorders
Frequency: 2 affected / 45 at risk

Adverse event: Renal impairment
Serious: no
Organ System: Renal and urinary disorders
Notes: 1 Renal impairment grade 3 in Arm A (1.5 mg plitidepsin).
Frequency: 2 affected / 45 at risk

Adverse event: Breast engorgement
Serious: no
Organ System: Reproductive system and breast disorders
Frequency: 1 affected / 45 at risk

Adverse event: Respiratory failure
Serious: no
Organ System: Respiratory, thoracic and mediastinal disorders
Frequency: 2 affected / 45 at risk

Adverse event: Chest discomfort
Serious: no
Organ System: Respiratory, thoracic and mediastinal disorders
Frequency: 1 affected / 45 at risk

Adverse event: Cough
Serious: no
Organ System: Respiratory, thoracic and mediastinal disorders
Frequency: 11 affected / 45 at risk

Adverse event: Dyspnoea
Serious: no
Organ System: Respiratory, thoracic and mediastinal disorders
Frequency: 7 affected / 45 at risk

Adverse event: Hypoxia
Serious: no
Organ System: Respiratory, thoracic and mediastinal disorders
Frequency: 2 affected / 45 at risk

Adverse event: Productive cough
Serious: no
Organ System: Respiratory, thoracic and mediastinal disorders
Frequency: 1 affected / 45 at risk

Adverse event: Respiratory distress
Serious: no
Organ System: Respiratory, thoracic and mediastinal disorders
Frequency: 1 affected / 45 at risk

Adverse event: Tachypnoea
Serious: no
Organ System: Respiratory, thoracic and mediastinal disorders
Frequency: 2 affected / 45 at risk

Adverse event: Skin ulcer
Serious: no
Organ System: Skin and subcutaneous tissue disorders
Frequency: 1 affected / 45 at risk

Adverse event: Hypertension
Serious: no
Organ System: Vascular disorders
Frequency: 2 affected / 45 at risk

Adverse event: Hypotension
Serious: no
Organ System: Vascular disorders
Frequency: 1 affected / 45 at risk

Adverse event: Phlebitis
Serious: no
Organ System: Vascular disorders
Frequency: 8 affected / 45 at risk

Adverse event: Thrombophlebitis
Serious: no
Organ System: Vascular disorders
Frequency: 1 affected / 45 at risk

Adverse event: Asthenia
Serious: no
Organ System: General disorders
Frequency: 6 affected / 45 at risk

Adverse event: Chest discomfort
Serious: no
Organ System: General disorders
Frequency: 1 affected / 45 at risk

Adverse event: Pyrexia
Serious: no
Organ System: General disorders
Frequency: 20 affected / 45 at risk

Adverse event: Malaise
Serious: no
Organ System: General disorders
Frequency: 1 affected / 45 at risk

Adverse event: Temperature regulation disorder
Serious: no
Organ System: General disorders
Frequency: 1 affected / 45 at risk

Adverse event: Fatigue
Serious: no
Organ System: General disorders
Frequency: 1 affected / 45 at risk

Adverse event: Platelet count decreased
Serious: no
Organ System: Investigations
Frequency: 1 affected / 45 at risk

Adverse event: Neutrophil count increased
Serious: no
Organ System: Investigations
Frequency: 1 affected / 45 at risk

Adverse event: Interleukin level increased
Serious: no
Organ System: Investigations
Frequency: 1 affected / 45 at risk

Adverse event: Lipase increased
Serious: no
Organ System: Investigations
Frequency: 1 affected / 45 at risk

Adverse event: Interstitial lung disease
Serious: no
Organ System: Respiratory, thoracic and mediastinal disorders
Frequency: 1 affected / 45 at risk

Adverse event: Pleuritic pain
Serious: no
Organ System: Respiratory, thoracic and mediastinal disorders
Frequency: 1 affected / 45 at risk

Adverse event: Pneumothorax spontaneous
Serious: no
Organ System: Respiratory, thoracic and mediastinal disorders
Frequency: 1 affected / 45 at risk

Adverse event: Tenosynovitis
Serious: no
Organ System: Musculoskeletal and connective tissue disorders
Frequency: 1 affected / 45 at risk