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| ID | Type | Description | Link |
|---|---|---|---|
| 2009-017119-13 | EudraCT Number |
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This trial is designed as a multi-centre, open label, dose-escalation, phase I trial and consists of five parts.
Part A investigates the safety and pharmacokinetics (PK) of escalating weekly dosing of Sym004 in patients with recurrent advanced solid tumors.
Part B and C validates the safety, PK and efficacy of weekly dosing of Sym004 at the maximum tolerated dose (MTD) in a homogenous patient population with advanced metastatic colorectal cancer (mCRC) and wild-type Kirsten rat sarcoma (KRAS). Part B will be initiated when a safe dose has been established in Part A.
If MTD equals 12 mg/kg, then part C will explore the 9 mg/kg level.
Part D and E is to validate the safety, PK and efficacy when administered every 2 weeks at doses of 12 mg/kg and 18 mg/kg, respectively.
Part F is to validate safety, PK and efficacy when administered with a single loading dose of 9 mg/kg followed by weekly doses of 6 mg/kg.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sym004 | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sym004 | Drug | In part A, patients in all dose cohorts will continue weekly treatment with the assigned dose of Sym004 until disease progression. In Part B, patients will continue weekly treatment with the tolerated dose of Sym004 until disease progression. In Part C, patients will receive weekly doses of Sym004 at the dose level below 12 mg/kg i.e. 9 mg/kg until disease progression. In Part D and E, patients will receive doses of Sym004 administered every 2 weeks at dose level 12 mg/kg and 18 mg/kg, respectively until disease progression. In Part F, patients will receive a single loading dose of 9 mg/kg followed by weekly doses of 6 mg/kg. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | The AEs were used as a primary endpoint. AEs were summarized using descriptive statistics and presented overall by system organ class and preferred term. The frequencies of AEs were presented including number and percentages of participants with events and the total number of events. | Visit 2 until first follow-up visit (up to 66 weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| Antitumor Activity | Best Overall Response (OR) on the Full Analysis Set (FAS) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, based on central evaluation with confirmatory CT scan or MRI [Complete Response (CR): disappearance of all target lesions; Partial Response (PR): at least a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD): at least a 20% increase in the sum of diameters of target lesions; Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; Overall Response (OR): CR + PR]. Baseline was defined as Visit 2 (pre-infusion). The outcome measure was measured from screening until PD. |
Not provided
Inclusion Criteria:
Part A:
1. Patients with refractory or recurrent advanced late stage solid tumors without available therapeutic options .
Part B, C, D, E and F:
Part A, B, C, D, E and F:
Exclusion Criteria:
Patients with clinically symptomatic brain metastases.
Received the following treatments prior to Visit 2:
Diarrhea CTCAE >1
Skin rash CTCAE >1
Abnormal organ or bone marrow function.
Use of immunosuppressive agents for the past 4 weeks prior to trial start, including systemic corticosteroids used at doses above 20mg/day of prednisolone or equivalent.
History of other malignancy within 5 years prior to trial start, with the exception of basal cell carcinoma of the skin and carcinoma in situ of the cervix (not in Part A).
Active severe infection, any other concurrent disease or medical conditions that are deemed to interfere with the conduct of the trial as judged by the investigator.
Known HIV positive
Known active hepatitis B or C
Patients with known uncontrolled allergic conditions or allergy to the study drug and/or their components.
Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months from Visit 1, congestive heart failure, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities and controlled and well treated chronic atrial fibrillation.
Significant concurrent, uncontrolled medical condition evaluated by the investigator to interfere with effect of the trial drug.
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| Name | Affiliation | Role |
|---|---|---|
| Josep Tabernero, MD, PhD | Vall d´Hebron University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| South Texas Accelerated Research Therapeutics (START) | San Antonio | Texas | 78229 | United States | ||
| UZ Brussel, Medische Oncologie |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25962717 | Derived | Dienstmann R, Patnaik A, Garcia-Carbonero R, Cervantes A, Benavent M, Rosello S, Tops BB, van der Post RS, Argiles G, Skartved NJ, Hansen UH, Hald R, Pedersen MW, Kragh M, Horak ID, Braun S, Van Cutsem E, Tolcher AW, Tabernero J. Safety and Activity of the First-in-Class Sym004 Anti-EGFR Antibody Mixture in Patients with Refractory Colorectal Cancer. Cancer Discov. 2015 Jun;5(6):598-609. doi: 10.1158/2159-8290.CD-14-1432. Epub 2015 May 11. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Part A: Dose Escalation | Dose escalation in patients with refractory or recurrent advanced solid tumors. Sym004: 0.4 mg/kg, 0.75 mg/kg, 1.5 mg/kg, 3 mg/kg, 6 mg/kg, 9 mg/kg, 12 mg/kg, weekly - i.v. infusions |
| FG001 | Part B: Dose Expansion Cohort | Dose expansion cohort in patients with advanced anti-epidermal growth factor receptor (anti-EGFR) antibody refractory metastatic colorectal cancer (mCRC). Sym004: 12 mg/kg, weekly - i.v. infusions |
| FG002 | Part C: Dose Expansion Cohort | Dose expansion cohort in patients with advanced anti-EGFR antibody refractory mCRC. Sym004: 9 mg/kg, weekly - i.v. infusions |
| FG003 | Part D: Dose Expansion Cohort | Dose expansion cohort in patients with advanced anti-EGFR antibody refractory mCRC. Sym004: 12 mg/kg, once every 2 weeks - i.v. infusions |
| FG004 | Part E: Dose Expansion Cohort | Dose expansion cohort in patients with advanced anti-EGFR antibody refractory mCRC. Sym004: 18 mg/kg, once every 2 weeks - i.v. infusions |
| FG005 | Part F: Dose Expansion Cohort | Dose expansion cohort in patients with advanced anti-EGFR antibody refractory mCRC. Sym004: 9 mg/kg loading dose followed by 6 mg/kg, weekly - i.v. infusions |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Part A: Dose escalation in patients with refractory or recurrent advanced solid tumors.
Parts B, C, D, E and F: Dose expansion cohorts in patients wíth advanced anti-EGFR antibody refractory mCRC.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Part A: Dose Escalation | Dose escalation in patients with refractory or recurrent advanced solid tumors. Sym004: 0.4 mg/kg, 0.75 mg/kg, 1.5 mg/kg, 3 mg/kg, 6 mg/kg, 9 mg/kg, 12 mg/kg, weekly - i.v. infusions |
| BG001 | Part B: Dose Expansion Cohort |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Adverse Events (AEs) | The AEs were used as a primary endpoint. AEs were summarized using descriptive statistics and presented overall by system organ class and preferred term. The frequencies of AEs were presented including number and percentages of participants with events and the total number of events. | Posted | Count of Participants | Participants | Visit 2 until first follow-up visit (up to 66 weeks) |
|
The Adverse Event (AE) reporting period for non-serious AEs started at Visit 2 (first dosing visit) and lasted until the first Follow-up Visit (4 weeks following last dose) or end of trial if the patient was withdrawn from the trial without the Follow-up Visits being performed. The AE reporting period for Serious Adverse Events (SAEs) started when the patient signed the informed consent and lasted until termination of the trial.
Any non-serious signs or symptoms occurring between Visit 1 and start of treatment at Visit 2 were recorded as medical history. In the survival period after end of trial, only SAEs with fatal outcome and SAEs considered related to Sym004 by the Investigator were collected.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part A: Dose Escalation | Dose escalation in patients with refractory or recurrent advanced solid tumors. Sym004 - 0.4 mg/kg, 0.75 mg/kg, 1.5 mg/kg, 3 mg/kg, 6 mg/kg, 9 mg/kg, 12 mg/kg, weekly - i.v. infusions |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Myocardial infarction | Cardiac disorders | MedDRA 15.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
None reported
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Scientific Officer | Symphogen A/S | +45 8838 2600 | info@symphogen.com |
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| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
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| ID | Term |
|---|---|
| C569270 | futuximab |
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|
| Up to 62 weeks |
| Antitumor Activity Endpoints - Time-to-event Endpoints | Median Progression Free Survival (PFS) was defined as the time interval without PD from start of first infusion until death or documented PD (i.e. at least a 20% increase in the sum of diameters of target lesions) according to RECIST v1.1. Patients who died without confirmed PD were considered as progressed. Patients who died or showed PD more than 21 days after last treatment were censored (i.e. were considered alive without progression on Day 21 after last treatment). Patients without events were censored at date of last scan or 22 days after last treatment, whichever occurred first. Median Overall Survival (OS) was defined as the time from start of first infusion until date of death from any cause. Patients alive at the time of the analysis or prematurely withdrawn from the trial (e.g. lost to follow-up or consent withdrawn) were censored for the OS analysis. In any case of censoring, the date of censoring was the last time point documenting survival status. | Up to 62 weeks |
| Terminal Half-Life (T½) | For Part A, the endpoint was not calculated. For Parts B, C and F, the endpoint was calculated for each patient following the first and fourth Sym004 infusions. For Parts D and E, the endpoint was calculated for each patient following the first and third Sym004 infusions. T½ was estimated using non-compartmental methods and actual time points. Outcome Measure Time Frame: Parts B, C and F (Weekly dosing): Sample collection at Visit 2 (1st dose from end of infusion, 1-, 2-, 4-, 8-, 24-, 48-hours) until 1 week post-infusion (168-hours) and at Visit 5 (4th dose from end of infusion, 1-, 2-, 4-, 8-, 24-hours) until 1 week post-infusion (168-hours). Parts D, E (Dosing every second week): Sample collection at Visit 2 (1st dose from end of infusion, 1-, 2-, 4-, 8-, 24-, 48-hours) to end of 3rd dose (from end of infusion, 1-, 2-, 4-, 8-, 24-hours) until 2 weeks post-infusion (336 hours). | See Time Frame in the Outcome Measure Description |
| Brussels |
| 1090 |
| Belgium |
| UZ Gasthuisberg, Digestive Oncology Unit | Brussels | 3000 | Belgium |
| UZ Antwerp, Oncologie | Edegem | 2650 | Belgium |
| Medical Oncology Department, Vall d´Hebron University Hospital | Barcelona | 08035 | Spain |
| Servicio de Oncología Médica, Hospital Universitario Virgen del Rocío | Seville | 41013 | Spain |
| Hospital Clínico Universitario de Valencia | Valencia | 46010 | Spain |
| Adverse Event |
|
| Death |
|
| Physician Decision |
|
| Withdrawal by Subject |
|
| Progressive disease |
|
Dose expansion cohort in patients with advanced anti-EGFR antibody refractory mCRC. Sym004: 12 mg/kg, weekly - i.v. infusions |
| BG002 | Part C: Dose Expansion Cohort | Dose expansion cohort in patients with advanced anti-EGFR antibody refractory mCRC. Sym004: 9 mg/kg, weekly - i.v. infusions |
| BG003 | Part D: Dose Expansion Cohort | Dose expansion cohort in patients with advanced anti-EGFR antibody refractory mCRC. Sym004: 12 mg/kg, once every 2 weeks - i.v. infusions |
| BG004 | Part E: Dose Expansion Cohort | Dose expansion cohort in patients with advanced anti-EGFR antibody refractory mCRC. Sym004: 18 mg/kg, once every 2 weeks - i.v. infusions |
| BG005 | Part F: Dose Expansion Cohort | Dose expansion cohort in patients with advanced anti-EGFR antibody refractory mCRC. Sym004: 9 mg/kg loading dose followed by 6 mg/kg, weekly - i.v. infusions |
| BG006 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Disease duration | Mean | Standard Deviation | years |
|
Dose expansion cohort in patients with advanced anti-EGFR antibody refractory mCRC.
Sym004: 12 mg/kg, weekly - i.v. infusions
| OG002 | Part C: Dose Expansion Cohort | Dose expansion cohort in patients with advanced anti-EGFR antibody refractory mCRC. Sym004: 9 mg/kg, weekly - i.v. infusions |
| OG003 | Part D: Dose Expansion Cohort | Dose expansion cohort in patients with advanced anti-EGFR antibody refractory mCRC. Sym004: 12 mg/kg, once every 2 weeks - i.v. infusions |
| OG004 | Part E: Dose Expansion Cohort | Dose expansion cohort in patients with advanced anti-EGFR antibody refractory mCRC. Sym004: 18 mg/kg, once every 2 weeks - i.v. infusions |
| OG005 | Part F: Dose Expansion Cohort | Dose expansion cohort in patients with advanced anti-EGFR antibody refractory mCRC. Sym004: 9 mg/kg loading dose followed by 6 mg/kg, weekly - i.v. infusions |
|
|
| Secondary | Antitumor Activity | Best Overall Response (OR) on the Full Analysis Set (FAS) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, based on central evaluation with confirmatory CT scan or MRI [Complete Response (CR): disappearance of all target lesions; Partial Response (PR): at least a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD): at least a 20% increase in the sum of diameters of target lesions; Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; Overall Response (OR): CR + PR]. Baseline was defined as Visit 2 (pre-infusion). The outcome measure was measured from screening until PD. | Data for Part A were presented only for the FAS. For Parts B to F, analyses and summaries were performed both for the FAS and for the per protocol population. The FAS was considered the primary analysis population. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to 62 weeks |
|
|
|
|
| Secondary | Antitumor Activity Endpoints - Time-to-event Endpoints | Median Progression Free Survival (PFS) was defined as the time interval without PD from start of first infusion until death or documented PD (i.e. at least a 20% increase in the sum of diameters of target lesions) according to RECIST v1.1. Patients who died without confirmed PD were considered as progressed. Patients who died or showed PD more than 21 days after last treatment were censored (i.e. were considered alive without progression on Day 21 after last treatment). Patients without events were censored at date of last scan or 22 days after last treatment, whichever occurred first. Median Overall Survival (OS) was defined as the time from start of first infusion until date of death from any cause. Patients alive at the time of the analysis or prematurely withdrawn from the trial (e.g. lost to follow-up or consent withdrawn) were censored for the OS analysis. In any case of censoring, the date of censoring was the last time point documenting survival status. | Posted | Median | 95% Confidence Interval | Months | Up to 62 weeks |
|
|
|
| Secondary | Terminal Half-Life (T½) | For Part A, the endpoint was not calculated. For Parts B, C and F, the endpoint was calculated for each patient following the first and fourth Sym004 infusions. For Parts D and E, the endpoint was calculated for each patient following the first and third Sym004 infusions. T½ was estimated using non-compartmental methods and actual time points. Outcome Measure Time Frame: Parts B, C and F (Weekly dosing): Sample collection at Visit 2 (1st dose from end of infusion, 1-, 2-, 4-, 8-, 24-, 48-hours) until 1 week post-infusion (168-hours) and at Visit 5 (4th dose from end of infusion, 1-, 2-, 4-, 8-, 24-hours) until 1 week post-infusion (168-hours). Parts D, E (Dosing every second week): Sample collection at Visit 2 (1st dose from end of infusion, 1-, 2-, 4-, 8-, 24-, 48-hours) to end of 3rd dose (from end of infusion, 1-, 2-, 4-, 8-, 24-hours) until 2 weeks post-infusion (336 hours). | For Part A, data could not be reported as the endpoint was not calculated and no pharmacokinetics (PK) analysis set was defined. For Parts B to F, a PK analysis set was used. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | See Time Frame in the Outcome Measure Description |
|
|
|
| 14 |
| 20 |
| 10 |
| 20 |
| 18 |
| 20 |
| EG001 | Part B: Dose Expansion Cohort | Dose expansion cohort in patients with advanced anti-EGFR antibody refractory mCRC. Sym004 - 12 mg/kg, weekly - i.v. infusions | 29 | 29 | 16 | 29 | 29 | 29 |
| EG002 | Part C: Dose Expansion Cohort | Dose expansion cohort in patients with advanced anti-EGFR antibody refractory mCRC. Sym004 - 9 mg/kg, weekly - i.v. infusions | 13 | 13 | 10 | 13 | 13 | 13 |
| EG003 | Part D: Dose Expansion Cohort | Dose expansion cohort in patients with advanced anti-EGFR antibody refractory mCRC. Sym004 - 12 mg/kg, once every 2 weeks - i.v. infusions | 9 | 12 | 7 | 12 | 12 | 12 |
| EG004 | Part E: Dose Expansion Cohort | Dose expansion cohort in patients with advanced anti-EGFR antibody refractory mCRC. Sym004 - 18 mg/kg, once every 2 weeks - i.v. infusions | 15 | 17 | 6 | 17 | 16 | 17 |
| EG005 | Part F: Dose Expansion Cohort | Dose expansion cohort in patients with advanced anti-EGFR antibody refractory mCRC. Sym004 - 9 mg/kg loading dose followed by 6 mg/kg, weekly - i.v. infusions | 14 | 20 | 7 | 20 | 20 | 20 |
| Ascites | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Pancreatic cyst | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Intestinal obstruction | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Subileus | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Gastric hemorrhage | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| General physical health deterioration | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Performance status decreased | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hyperbilirubinemia | Hepatobiliary disorders | MedDRA 15.1 | Systematic Assessment |
|
| Cholangitis | Hepatobiliary disorders | MedDRA 15.1 | Systematic Assessment |
|
| Jaundice | Hepatobiliary disorders | MedDRA 15.1 | Systematic Assessment |
|
| Jaundice cholestatic | Hepatobiliary disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hypersensitivity | Immune system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Abdominal abscess | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Esophageal candidiasis | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Peritonitis | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Catheter site infection | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Endocarditis | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Fracture | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
|
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
|
| Spinal fracture | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Hypocalcemia | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hypomagnesemia | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hypophosphatemia | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 15.1 | Systematic Assessment |
|
| Metastases to central nervous system | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 15.1 | Systematic Assessment |
|
| Tumor pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 15.1 | Systematic Assessment |
|
| Spinal cord compression | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Obstructive uropathy | Renal and urinary disorders | MedDRA 15.1 | Systematic Assessment |
|
| Renal failure acute | Renal and urinary disorders | MedDRA 15.1 | Systematic Assessment |
|
| Bronchospasm | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Dermatosis | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Shock | Vascular disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hypovolemic shock | Vascular disorders | MedDRA 15.1 | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Skin fissures | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Eczema | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hypertrichosis | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Nail toxicity | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Onycholysis | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Pain of skin | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Scab | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Skin exfoliation | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Mucosal inflammation | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Xerosis | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Edema peripheral | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Edema | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Chills | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Device occlusion | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hemorrhoids | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hypomagnesemia | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hypocalcemia | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hypokalemia | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hypophosphatemia | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hyperkalemia | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hypoalbuminemia | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Iron deficiency | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hypertriglyceridemia | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Paronychia | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Superinfection | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Respiratory tract infection | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
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| Skin infection | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
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| Fungal infection | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
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| Nail infection | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Blood alkaline phosphatase increase | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Blood magnesium decreased | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Hemoglobin decreased | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Body temperature decreased | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Amylase increased | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Blood albumin decreased | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Lipase increased | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Conjunctivitis | Eye disorders | MedDRA 15.1 | Systematic Assessment |
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| Dry eye | Eye disorders | MedDRA 15.1 | Systematic Assessment |
|
| Blepharitis | Eye disorders | MedDRA 15.1 | Systematic Assessment |
|
| Lacrimation increased | Eye disorders | MedDRA 15.1 | Systematic Assessment |
|
| Ocular icterus | Eye disorders | MedDRA 15.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Groin pain | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
|
| Ligament sprain | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
|
| Toxicity to various agents | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Leukocytosis | Blood and lymphatic system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hyperbilirubinemia | Hepatobiliary disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hepatic pain | Hepatobiliary disorders | MedDRA 15.1 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
|
| Tumor pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 15.1 | Systematic Assessment |
|
| Tumor associated fever | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 15.1 | Systematic Assessment |
|
| Hypersensitivity | Immune system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 15.1 | Systematic Assessment |
|
| Trichomegaly | Congenital, familial and genetic disorders | MedDRA 15.1 | Systematic Assessment |
|
| Metrorrhagia | Reproductive system and breast disorders | MedDRA 15.1 | Systematic Assessment |
|
| Atrophic vulvovaginitis | Reproductive system and breast disorders | MedDRA 15.1 | Systematic Assessment |
|
| Pruritus genital | Reproductive system and breast disorders | MedDRA 15.1 | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA 15.1 | Systematic Assessment |
|
| Leukocyturia | Renal and urinary disorders | MedDRA 15.1 | Systematic Assessment |
|
| Urinary incontinence | Renal and urinary disorders | MedDRA 15.1 | Systematic Assessment |
|
Not provided
Not provided
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| Progressive Disease |
|
| Partial Response |
|
| Missing |
|
| Not Evaluable |
|
| Overall Survival |
|
| 3rd Dose |
|
| 4th Dose |
|