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Sym004 in Subjects With Stage IV Non-small Cell Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02083679
Recruitment Status : Terminated (Sponsor the return rights of the compound to the collaboration partner for further clinical development)
First Posted : March 11, 2014
Results First Posted : October 25, 2016
Last Update Posted : October 25, 2016
Sponsor:
Information provided by (Responsible Party):
EMD Serono

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Carcinoma, Non-Small-Cell Lung
Interventions Drug: Part 1: Sym004 6 mg/kg + Cisplatin/Gemcitabine
Drug: Part 1: Sym004 6 mg/kg + Cisplatin/Pemetrexed
Drug: Part 1: Sym004 6 mg/kg + Carboplatin/Paclitaxel
Drug: Part 1: Sym004 6/12 mg/kg + Carboplatin/Paclitaxel
Enrollment 15
Recruitment Details The trial was conducted at 5 clinical trial sites within France and the United States. First subject first visit: 03 July 2014 and last subject last visit: 31 August 2015. Clinical data cut-off date: 16 September 2015
Pre-assignment Details This study was planned to be conducted in 2 parts; Part 1 was the dose escalation part and Part 2 was the expansion cohort. However, due to premature termination of the trial by the Sponsor, the Expansion Cohort (Part 2) was not conducted.
Arm/Group Title Part 1: Sym004 6 mg/kg + Cisplatin/Gemcitabine Part 1: Sym004 6 mg/kg + Cisplatin/Pemetrexed Part 1: Sym004 6 mg/kg + Carboplatin/Paclitaxel Part 1: Sym004 6/12 mg/kg + Carboplatin/Paclitaxel
Hide Arm/Group Description Sym004 administered as an intravenous infusion at a dose of 6 milligram per kilogram (mg/kg) weekly until unacceptable toxicity, progressive disease, withdrawal of consent, or until the subject met any of the criteria for subject withdrawal, or withdrawal from the investigational medicinal product (IMP) in combination with platinum-doublet chemotherapy regimen of cisplatin/gemcitabine (cisplatin 75 milligram per meter square (mg/m^2) on Day 1 plus gemcitabine 1250 mg/m^2 on Days 1 and 8 of every 3-Week cycle intravenously for a maximum of 6 treatment cycles). Sym004 administered as an intravenous infusion at a dose 6 mg/kg weekly until unacceptable toxicity, progressive disease, withdrawal of consent, or until the subject met any of the criteria for subject withdrawal, or withdrawal from the IMP in combination with platinum-doublet chemotherapy regimen of cisplatin/pemetrexed (cisplatin 75 mg/m^2 plus pemetrexed 500 mg/m^2 on Day 1 of every 3-Week cycle intravenously for a maximum of 6 treatment cycles). Sym004 administered as an intravenous infusion at a dose 6 mg/kg weekly until unacceptable toxicity, progressive disease, withdrawal of consent, or until the subject met any of the criteria for subject withdrawal, or withdrawal from the IMP in combination with platinum-doublet chemotherapy regimen of carboplatin/paclitaxel (carboplatin area under the concentration-time curve (AUC) = 6 milligram per millilitre per minute [mg/mL/min] plus paclitaxel 225 mg/m^2 on Day 1 of 3-Week cycle intravenously for a maximum of 6 treatment cycles). Sym004 administered as an intravenous infusion at a dose 6 mg/kg on Day 1 and 12 mg/kg on Day 8 of a 3-Week cycle until unacceptable toxicity, progressive disease, withdrawal of consent, or until the subject met any of the criteria for subject withdrawal, or withdrawal from the IMP in combination with platinum-doublet chemotherapy regimen of carboplatin/paclitaxel (carboplatin AUC = 6 mg/mL/min plus paclitaxel 225 mg/m^2 on Day 1 of every 3-Week cycle intravenously for a maximum of 6 treatment cycles).
Period Title: Overall Study
Started 3 6 3 3
Completed 3 6 3 3
Not Completed 0 0 0 0
Arm/Group Title Part 1: Sym004 6 mg/kg + Cisplatin/Gemcitabine Part 1: Sym004 6 mg/kg + Cisplatin/Pemetrexed Part 1: Sym004 6 mg/kg + Carboplatin/Paclitaxel Part 1: Sym004 6/12 mg/kg + Carboplatin/Paclitaxel Total
Hide Arm/Group Description Sym004 administered as an intravenous infusion at a dose of 6 milligram per kilogram (mg/kg) weekly until unacceptable toxicity, progressive disease, withdrawal of consent, or until the subject met any of the criteria for subject withdrawal, or withdrawal from the investigational medicinal product (IMP) in combination with platinum-doublet chemotherapy regimen of cisplatin/gemcitabine (cisplatin 75 milligram per meter square (mg/m^2) on Day 1 plus gemcitabine 1250 mg/m^2 on Days 1 and 8 of every 3-Week cycle intravenously for a maximum of 6 treatment cycles). Sym004 administered as an intravenous infusion at a dose 6 mg/kg weekly until unacceptable toxicity, progressive disease, withdrawal of consent, or until the subject met any of the criteria for subject withdrawal, or withdrawal from the IMP in combination with platinum-doublet chemotherapy regimen of cisplatin/pemetrexed (cisplatin 75 mg/m^2 plus pemetrexed 500 mg/m^2 on Day 1 of every 3-Week cycle intravenously for a maximum of 6 treatment cycles). Sym004 administered as an intravenous infusion at a dose 6 mg/kg weekly until unacceptable toxicity, progressive disease, withdrawal of consent, or until the subject met any of the criteria for subject withdrawal, or withdrawal from the IMP in combination with platinum-doublet chemotherapy regimen of carboplatin/paclitaxel (carboplatin area under the concentration-time curve (AUC) = 6 milligram per millilitre per minute [mg/mL/min] plus paclitaxel 225 mg/m^2 on Day 1 of 3-Week cycle intravenously for a maximum of 6 treatment cycles). Sym004 administered as an intravenous infusion at a dose 6 mg/kg on Day 1 and 12 mg/kg on Day 8 of a 3-Week cycle until unacceptable toxicity, progressive disease, withdrawal of consent, or until the subject met any of the criteria for subject withdrawal, or withdrawal from the IMP in combination with platinum-doublet chemotherapy regimen of carboplatin/paclitaxel (carboplatin AUC = 6 mg/mL/min plus paclitaxel 225 mg/m^2 on Day 1 of every 3-Week cycle intravenously for a maximum of 6 treatment cycles). Total of all reporting groups
Overall Number of Baseline Participants 3 6 3 3 15
Hide Baseline Analysis Population Description
The safety analysis set included all 15 subjects who were administered any dose of the trial medication.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 3 participants 6 participants 3 participants 3 participants 15 participants
61.8  (7.05) 59.1  (6.44) 58.9  (11.09) 44.8  (10.86) 56.7  (9.78)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 6 participants 3 participants 3 participants 15 participants
Female
0
   0.0%
2
  33.3%
1
  33.3%
0
   0.0%
3
  20.0%
Male
3
 100.0%
4
  66.7%
2
  66.7%
3
 100.0%
12
  80.0%
1.Primary Outcome
Title Number of Subjects With Dose Limiting Toxicities (DLTs)
Hide Description DLT: any National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03 Grade 4 hematologic or Grade 3/4 non-hematologic toxicities that occurred during DLT observation period and were considered by Investigator to be at least possibly related to trial treatment, and were confirmed by Safety Monitoring Committee (SMC), with exception of Grade 4 neutropenia for not >5 days; Grade 4 lymphocytopenia/ thrombocytopenia for not >5 days; fatigue/headache lasting < 7 days; nausea/vomiting/diarrhoea lasting not >3 days; asymptomatic Grade 3 increase in liver function tests that resolve to baseline within 7 days; Mucositis >= Grade 3 lasting < 7 days; Grade 3 hyperglycemia that resolves in < 7 days; any laboratory values >Grade 3 without any clinical correlate (resolve within 5 days); Grade 3 skin toxicities that resolve to Grade 2 within 7 days; Grade 3/4 hypomagnesemia that resolves within 5 days. Subjects with DLTs presented based on investigator and SMC decision.
Time Frame Day 1 to Day 21 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
The dose limiting toxicity set included all 15 subjects in the safety analysis set (SAF) who received all planned trial medication doses during the first 21 days following the first dose of Sym004.
Arm/Group Title Part 1: Sym004 6 mg/kg + Cisplatin/Gemcitabine Part 1: Sym004 6 mg/kg + Cisplatin/Pemetrexed Part 1: Sym004 6 mg/kg + Carboplatin/Paclitaxel Part 1: Sym004 6/12 mg/kg + Carboplatin/Paclitaxel
Hide Arm/Group Description:
Sym004 administered as an intravenous infusion at a dose of 6 milligram per kilogram (mg/kg) weekly until unacceptable toxicity, progressive disease, withdrawal of consent, or until the subject met any of the criteria for subject withdrawal, or withdrawal from the investigational medicinal product (IMP) in combination with platinum-doublet chemotherapy regimen of cisplatin/gemcitabine (cisplatin 75 milligram per meter square (mg/m^2) on Day 1 plus gemcitabine 1250 mg/m^2 on Days 1 and 8 of every 3-Week cycle intravenously for a maximum of 6 treatment cycles).
Sym004 administered as an intravenous infusion at a dose 6 mg/kg weekly until unacceptable toxicity, progressive disease, withdrawal of consent, or until the subject met any of the criteria for subject withdrawal, or withdrawal from the IMP in combination with platinum-doublet chemotherapy regimen of cisplatin/pemetrexed (cisplatin 75 mg/m^2 plus pemetrexed 500 mg/m^2 on Day 1 of every 3-Week cycle intravenously for a maximum of 6 treatment cycles).
Sym004 administered as an intravenous infusion at a dose 6 mg/kg weekly until unacceptable toxicity, progressive disease, withdrawal of consent, or until the subject met any of the criteria for subject withdrawal, or withdrawal from the IMP in combination with platinum-doublet chemotherapy regimen of carboplatin/paclitaxel (carboplatin area under the concentration-time curve (AUC) = 6 milligram per millilitre per minute [mg/mL/min] plus paclitaxel 225 mg/m^2 on Day 1 of 3-Week cycle intravenously for a maximum of 6 treatment cycles).
Sym004 administered as an intravenous infusion at a dose 6 mg/kg on Day 1 and 12 mg/kg on Day 8 of a 3-Week cycle until unacceptable toxicity, progressive disease, withdrawal of consent, or until the subject met any of the criteria for subject withdrawal, or withdrawal from the IMP in combination with platinum-doublet chemotherapy regimen of carboplatin/paclitaxel (carboplatin AUC = 6 mg/mL/min plus paclitaxel 225 mg/m^2 on Day 1 of every 3-Week cycle intravenously for a maximum of 6 treatment cycles).
Overall Number of Participants Analyzed 3 6 3 3
Measure Type: Number
Unit of Measure: Subjects
Investigator 2 1 1 0
SMC 2 1 0 0
2.Secondary Outcome
Title Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation and TEAEs Leading to Death
Hide Description An adverse event (AE) was defined as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. AEs were considered treatment emergent if they started on or after the day of first administration of the first trial treatment given (Sym004 or one of the individual Platinum-Doublet therapies) or if they worsened after receiving first dose of treatment.
Time Frame Day 1 up to 28 days after last dose of study drug (up to 53 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all 15 subjects who were administered any dose of the trial medication.
Arm/Group Title Part 1: Sym004 6 mg/kg + Cisplatin/Gemcitabine Part 1: Sym004 6 mg/kg + Cisplatin/Pemetrexed Part 1: Sym004 6 mg/kg + Carboplatin/Paclitaxel Part 1: Sym004 6/12 mg/kg + Carboplatin/Paclitaxel
Hide Arm/Group Description:
Sym004 administered as an intravenous infusion at a dose of 6 milligram per kilogram (mg/kg) weekly until unacceptable toxicity, progressive disease, withdrawal of consent, or until the subject met any of the criteria for subject withdrawal, or withdrawal from the investigational medicinal product (IMP) in combination with platinum-doublet chemotherapy regimen of cisplatin/gemcitabine (cisplatin 75 milligram per meter square (mg/m^2) on Day 1 plus gemcitabine 1250 mg/m^2 on Days 1 and 8 of every 3-Week cycle intravenously for a maximum of 6 treatment cycles).
Sym004 administered as an intravenous infusion at a dose 6 mg/kg weekly until unacceptable toxicity, progressive disease, withdrawal of consent, or until the subject met any of the criteria for subject withdrawal, or withdrawal from the IMP in combination with platinum-doublet chemotherapy regimen of cisplatin/pemetrexed (cisplatin 75 mg/m^2 plus pemetrexed 500 mg/m^2 on Day 1 of every 3-Week cycle intravenously for a maximum of 6 treatment cycles).
Sym004 administered as an intravenous infusion at a dose 6 mg/kg weekly until unacceptable toxicity, progressive disease, withdrawal of consent, or until the subject met any of the criteria for subject withdrawal, or withdrawal from the IMP in combination with platinum-doublet chemotherapy regimen of carboplatin/paclitaxel (carboplatin area under the concentration-time curve (AUC) = 6 milligram per millilitre per minute [mg/mL/min] plus paclitaxel 225 mg/m^2 on Day 1 of 3-Week cycle intravenously for a maximum of 6 treatment cycles).
Sym004 administered as an intravenous infusion at a dose 6 mg/kg on Day 1 and 12 mg/kg on Day 8 of a 3-Week cycle until unacceptable toxicity, progressive disease, withdrawal of consent, or until the subject met any of the criteria for subject withdrawal, or withdrawal from the IMP in combination with platinum-doublet chemotherapy regimen of carboplatin/paclitaxel (carboplatin AUC = 6 mg/mL/min plus paclitaxel 225 mg/m^2 on Day 1 of every 3-Week cycle intravenously for a maximum of 6 treatment cycles).
Overall Number of Participants Analyzed 3 6 3 3
Measure Type: Number
Unit of Measure: subjects
TEAEs 3 6 3 3
Serious TEAEs 3 5 3 3
TEAE leading to Discontinuation 1 3 0 2
TEAEs Leading to Death 0 0 0 0
Time Frame Day 1 up to 28 days after last dose of study drug (up to 53 weeks)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Part 1: Sym004 6 mg/kg + Cisplatin/Gemcitabine Part 1: Sym004 6 mg/kg + Cisplatin/Pemetrexed Part 1: Sym004 6 mg/kg + Carboplatin/Paclitaxel Part 1: Sym004 6/12 mg/kg + Carboplatin/Paclitaxel
Hide Arm/Group Description Sym004 administered as an intravenous infusion at a dose of 6 milligram per kilogram (mg/kg) weekly until unacceptable toxicity, progressive disease, withdrawal of consent, or until the subject met any of the criteria for subject withdrawal, or withdrawal from the investigational medicinal product (IMP) in combination with platinum-doublet chemotherapy regimen of cisplatin/gemcitabine (cisplatin 75 milligram per meter square (mg/m^2) on Day 1 plus gemcitabine 1250 mg/m^2 on Days 1 and 8 of every 3-Week cycle intravenously for a maximum of 6 treatment cycles). Sym004 administered as an intravenous infusion at a dose 6 mg/kg weekly until unacceptable toxicity, progressive disease, withdrawal of consent, or until the subject met any of the criteria for subject withdrawal, or withdrawal from the IMP in combination with platinum-doublet chemotherapy regimen of cisplatin/pemetrexed (cisplatin 75 mg/m^2 plus pemetrexed 500 mg/m^2 on Day 1 of every 3-Week cycle intravenously for a maximum of 6 treatment cycles). Sym004 administered as an intravenous infusion at a dose 6 mg/kg weekly until unacceptable toxicity, progressive disease, withdrawal of consent, or until the subject met any of the criteria for subject withdrawal, or withdrawal from the IMP in combination with platinum-doublet chemotherapy regimen of carboplatin/paclitaxel (carboplatin area under the concentration-time curve (AUC) = 6 milligram per millilitre per minute [mg/mL/min] plus paclitaxel 225 mg/m^2 on Day 1 of 3-Week cycle intravenously for a maximum of 6 treatment cycles). Sym004 administered as an intravenous infusion at a dose 6 mg/kg on Day 1 and 12 mg/kg on Day 8 of a 3-Week cycle until unacceptable toxicity, progressive disease, withdrawal of consent, or until the subject met any of the criteria for subject withdrawal, or withdrawal from the IMP in combination with platinum-doublet chemotherapy regimen of carboplatin/paclitaxel (carboplatin AUC = 6 mg/mL/min plus paclitaxel 225 mg/m^2 on Day 1 of every 3-Week cycle intravenously for a maximum of 6 treatment cycles).
All-Cause Mortality
Part 1: Sym004 6 mg/kg + Cisplatin/Gemcitabine Part 1: Sym004 6 mg/kg + Cisplatin/Pemetrexed Part 1: Sym004 6 mg/kg + Carboplatin/Paclitaxel Part 1: Sym004 6/12 mg/kg + Carboplatin/Paclitaxel
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Part 1: Sym004 6 mg/kg + Cisplatin/Gemcitabine Part 1: Sym004 6 mg/kg + Cisplatin/Pemetrexed Part 1: Sym004 6 mg/kg + Carboplatin/Paclitaxel Part 1: Sym004 6/12 mg/kg + Carboplatin/Paclitaxel
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/3 (100.00%)   5/6 (83.33%)   3/3 (100.00%)   3/3 (100.00%) 
Blood and lymphatic system disorders         
Thrombocytopenia * 1  1/3 (33.33%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Cardiac disorders         
Atrial fibrillation * 1  0/3 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Ear and labyrinth disorders         
Hearing impaired * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Gastrointestinal disorders         
Abdominal pain * 1  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%) 
Abdominal pain upper * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Nausea * 1  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%) 
Small intestinal obstruction * 1  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%) 
Stomatitis * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Vomiting * 1  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%) 
General disorders         
Non-cardiac chest pain * 1  0/3 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Infections and infestations         
Bacterial sepsis * 1  1/3 (33.33%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Device related infection * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Device related sepsis * 1  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%) 
Staphylococcal sepsis * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Injury, poisoning and procedural complications         
Infusion related reaction * 1  0/3 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Investigations         
Neutrophil count decreased * 1  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%) 
Platelet count decreased * 1  1/3 (33.33%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
White blood cell count decreased * 1  1/3 (33.33%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Metabolism and nutrition disorders         
Diabetes mellitus * 1  0/3 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Hypomagnesaemia * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Musculoskeletal and connective tissue disorders         
Back pain * 1  0/3 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Transitional cell carcinoma * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Nervous system disorders         
Syncope * 1  0/3 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Tremor * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Renal and urinary disorders         
Acute kidney injury * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  1/3 (33.33%) 
Urinary bladder polyp * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Dyspnoea * 1  0/3 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Pneumothorax * 1  2/3 (66.67%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Pulmonary embolism * 1  1/3 (33.33%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Vascular disorders         
Deep vein thrombosis * 1  1/3 (33.33%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Peripheral vascular disorder * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 18.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Part 1: Sym004 6 mg/kg + Cisplatin/Gemcitabine Part 1: Sym004 6 mg/kg + Cisplatin/Pemetrexed Part 1: Sym004 6 mg/kg + Carboplatin/Paclitaxel Part 1: Sym004 6/12 mg/kg + Carboplatin/Paclitaxel
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/3 (100.00%)   6/6 (100.00%)   3/3 (100.00%)   3/3 (100.00%) 
Blood and lymphatic system disorders         
Anaemia * 1  3/3 (100.00%)  6/6 (100.00%)  2/3 (66.67%)  1/3 (33.33%) 
Leukopenia * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Neutropenia * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Thrombocytosis * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Cardiac disorders         
Angina pectoris * 1  0/3 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Atrial fibrillation * 1  1/3 (33.33%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Sinus tachycardia * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Tachycardia * 1  0/3 (0.00%)  1/6 (16.67%)  1/3 (33.33%)  1/3 (33.33%) 
Ear and labyrinth disorders         
Hearing impaired * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Endocrine disorders         
Adrenal insufficiency * 1  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%) 
Gastrointestinal disorders         
Abdominal pain * 1  0/3 (0.00%)  3/6 (50.00%)  1/3 (33.33%)  2/3 (66.67%) 
Cheilitis * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Constipation * 1  1/3 (33.33%)  3/6 (50.00%)  0/3 (0.00%)  2/3 (66.67%) 
Diarrhoea * 1  0/3 (0.00%)  2/6 (33.33%)  0/3 (0.00%)  0/3 (0.00%) 
Dyspepsia * 1  1/3 (33.33%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Gastrooesophageal reflux disease * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Lip oedema * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Nausea * 1  0/3 (0.00%)  5/6 (83.33%)  2/3 (66.67%)  2/3 (66.67%) 
Odynophagia * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Stomatitis * 1  2/3 (66.67%)  3/6 (50.00%)  2/3 (66.67%)  1/3 (33.33%) 
Tongue discolouration * 1  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%) 
Vomiting * 1  0/3 (0.00%)  1/6 (16.67%)  2/3 (66.67%)  1/3 (33.33%) 
General disorders         
Asthenia * 1  1/3 (33.33%)  3/6 (50.00%)  2/3 (66.67%)  1/3 (33.33%) 
Chills * 1  1/3 (33.33%)  2/6 (33.33%)  0/3 (0.00%)  0/3 (0.00%) 
Hyperthermia * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Impaired healing * 1  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%) 
Malaise * 1  0/3 (0.00%)  2/6 (33.33%)  1/3 (33.33%)  1/3 (33.33%) 
Non-cardiac chest pain * 1  0/3 (0.00%)  1/6 (16.67%)  1/3 (33.33%)  0/3 (0.00%) 
Oedema peripheral * 1  0/3 (0.00%)  2/6 (33.33%)  1/3 (33.33%)  0/3 (0.00%) 
Pain * 1  0/3 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Pyrexia * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  1/3 (33.33%) 
Sense of oppression * 1  0/3 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Thrombosis in device * 1  1/3 (33.33%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Xerosis * 1  0/3 (0.00%)  3/6 (50.00%)  1/3 (33.33%)  0/3 (0.00%) 
Immune system disorders         
Drug hypersensitivity * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Infections and infestations         
Conjunctivitis * 1  0/3 (0.00%)  3/6 (50.00%)  0/3 (0.00%)  0/3 (0.00%) 
Folliculitis * 1  0/3 (0.00%)  3/6 (50.00%)  2/3 (66.67%)  0/3 (0.00%) 
Fungal infection * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Gastroenteritis * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Genital infection fungal * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Oral candidiasis * 1  0/3 (0.00%)  2/6 (33.33%)  0/3 (0.00%)  0/3 (0.00%) 
Oral fungal infection * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Paronychia * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Injury, poisoning and procedural complications         
Excoriation * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Infusion related reaction * 1  2/3 (66.67%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Overdose * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Investigations         
Alanine aminotransferase increased * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Aspartate aminotransferase increased * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Blood alkaline phosphatase increased * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Blood creatinine increased * 1  0/3 (0.00%)  2/6 (33.33%)  0/3 (0.00%)  0/3 (0.00%) 
Gamma-glutamyltransferase increased * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
General physical condition abnormal * 1  0/3 (0.00%)  1/6 (16.67%)  1/3 (33.33%)  0/3 (0.00%) 
Lymphocyte count decreased * 1  0/3 (0.00%)  3/6 (50.00%)  2/3 (66.67%)  1/3 (33.33%) 
Neutrophil count decreased * 1  3/3 (100.00%)  5/6 (83.33%)  2/3 (66.67%)  2/3 (66.67%) 
Platelet count decreased * 1  1/3 (33.33%)  3/6 (50.00%)  2/3 (66.67%)  2/3 (66.67%) 
Prothrombin time prolonged * 1  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%) 
Weight decreased * 1  0/3 (0.00%)  2/6 (33.33%)  2/3 (66.67%)  1/3 (33.33%) 
White blood cell count decreased * 1  2/3 (66.67%)  2/6 (33.33%)  3/3 (100.00%)  1/3 (33.33%) 
Metabolism and nutrition disorders         
Decreased appetite * 1  2/3 (66.67%)  3/6 (50.00%)  2/3 (66.67%)  1/3 (33.33%) 
Dehydration * 1  1/3 (33.33%)  1/6 (16.67%)  0/3 (0.00%)  2/3 (66.67%) 
Hyperglycaemia * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Hyperuricaemia * 1  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%) 
Hypoalbuminaemia * 1  0/3 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Hypocalcaemia * 1  1/3 (33.33%)  1/6 (16.67%)  0/3 (0.00%)  1/3 (33.33%) 
Hypochloraemia * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Hypokalaemia * 1  2/3 (66.67%)  2/6 (33.33%)  2/3 (66.67%)  0/3 (0.00%) 
Hypomagnesaemia * 1  1/3 (33.33%)  4/6 (66.67%)  3/3 (100.00%)  2/3 (66.67%) 
Hyponatraemia * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  1/3 (33.33%) 
Hypophosphataemia * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  1/3 (33.33%) 
Musculoskeletal and connective tissue disorders         
Clubbing * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Muscular weakness * 1  0/3 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Musculoskeletal chest pain * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Neck pain * 1  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%) 
Pain in extremity * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  2/3 (66.67%) 
Spinal pain * 1  0/3 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Nervous system disorders         
Balance disorder * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Cerebellar syndrome * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Dizziness * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Dysgeusia * 1  1/3 (33.33%)  3/6 (50.00%)  2/3 (66.67%)  1/3 (33.33%) 
Headache * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Neuropathy peripheral * 1  0/3 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Paraesthesia * 1  0/3 (0.00%)  1/6 (16.67%)  1/3 (33.33%)  1/3 (33.33%) 
Polyneuropathy * 1  0/3 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Somnolence * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Syncope * 1  0/3 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Tremor * 1  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%) 
Psychiatric disorders         
Confusional state * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Depressive symptom * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Renal and urinary disorders         
Acute kidney injury * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  1/3 (33.33%) 
Cystitis noninfective * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Haematuria * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Urinary bladder polyp * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Urinary retention * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Reproductive system and breast disorders         
Genital erythema * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Bradypnoea * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Cough * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Dyspnoea * 1  1/3 (33.33%)  3/6 (50.00%)  1/3 (33.33%)  1/3 (33.33%) 
Emphysema * 1  1/3 (33.33%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Epistaxis * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Haemoptysis * 1  0/3 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Pleural effusion * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Pulmonary embolism * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Sinus congestion * 1  1/3 (33.33%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%) 
Skin and subcutaneous tissue disorders         
Alopecia * 1  0/3 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  1/3 (33.33%) 
Decubitus ulcer * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  1/3 (33.33%) 
Dermatitis acneiform * 1  2/3 (66.67%)  1/6 (16.67%)  1/3 (33.33%)  2/3 (66.67%) 
Dry skin * 1  0/3 (0.00%)  1/6 (16.67%)  1/3 (33.33%)  1/3 (33.33%) 
Erythema * 1  0/3 (0.00%)  2/6 (33.33%)  0/3 (0.00%)  0/3 (0.00%) 
Hirsutism * 1  0/3 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Hyperkeratosis * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Papule * 1  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%) 
Pigmentation disorder * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
Rash * 1  0/3 (0.00%)  2/6 (33.33%)  0/3 (0.00%)  1/3 (33.33%) 
Rash maculo-papular * 1  1/3 (33.33%)  1/6 (16.67%)  1/3 (33.33%)  1/3 (33.33%) 
Rash papular * 1  0/3 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%) 
Skin fissures * 1  0/3 (0.00%)  2/6 (33.33%)  0/3 (0.00%)  0/3 (0.00%) 
Skin hyperpigmentation * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  1/3 (33.33%) 
Skin ulcer * 1  0/3 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Vascular disorders         
Hypertension * 1  1/3 (33.33%)  1/6 (16.67%)  1/3 (33.33%)  0/3 (0.00%) 
Peripheral artery thrombosis * 1  0/3 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 18.0
The trial was prematurely discontinued and Expansion Cohort (Part 2) was not conducted as Sponsor decided to prematurely discontinue the development of Sym004. This decision was not related to any safety or efficacy findings regarding Sym004.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Merck KGaA Communication Center
Organization: Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany
Phone: +49-6151-72-5200
Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT02083679     History of Changes
Other Study ID Numbers: EMR200637-003
2013-003995-11 ( EudraCT Number )
First Submitted: March 7, 2014
First Posted: March 11, 2014
Results First Submitted: August 29, 2016
Results First Posted: October 25, 2016
Last Update Posted: October 25, 2016