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| ID | Type | Description | Link |
|---|---|---|---|
| CP11-0907 | Other Identifier | ImClone Systems | |
| I4X-IE-JFCA | Other Identifier | Eli Lilly | |
| 21-1901 | Other Identifier | PMDA (MoH) in Japan |
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| Name | Class |
|---|---|
| Parexel | INDUSTRY |
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This study is to establish the safety and pharmacokinetic (PK) profile of IMC-11F8, administered either: (1) in a 3-week cycle; or (2) in a 2-week cycle to Japanese participants with advanced solid tumors who have not responded to standard therapy or for whom no standard therapy is available.
This single center, open-label, single-arm, Phase 1 study will enroll 18 participants at a maximum. The actual size will vary depending on the dose-limiting toxicities (DLTs) observed and the resultant sizes of the cohorts. Participants will receive IMC-11F8 administered intravenously, once every 2 weeks or on Days 1 and 8 every 3 weeks for 6 weeks (1 cycle). All infusions can be administered within ± 1 day of the scheduled administration date. After 1 cycle of treatment, participants who have an objective response or stable disease may continue to receive IMC-11F8 at the same dose and schedule until disease progression or other withdrawal criteria are met.
A minimum of 3 participants will be enrolled in each cohort. Dose escalation in successive cohorts will occur once all participants complete 1 cycle of therapy.
Participants will be enrolled sequentially into each cohort. A completed participant will be either a participant who completes the initial 6-week treatment period (Cycle 1) or a participant who discontinues therapy for an IMC-11F8-related toxicity during Cycle 1. Participants who do not complete the first 6 weeks of treatment for reasons other than an IMC-11F8-related toxicity will be replaced. Toxicity data for each cohort will be reviewed prior to dose escalation. Upon completion of all required safety evaluations during the initial 6 weeks, the next cohort of new participants will be treated at the next higher dose level using a dose escalation scheme.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental |
| |
| Cohort 2 | Experimental |
| |
| Cohort 3 | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IMC-11F8 | Biological | 600 milligrams (mg) intravenously, Days 1 and 8 every 3 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With 1 or More Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) | Data presented are the number of participants who experienced 1 or more TEAEs or SAEs regardless of causality. An adverse event was considered as TEAE if it occurred any time after the administration of the first dose of study drug or up to 30 days after the last dose of study treatment or if it occurred prior to the first dose and worsened while on treatment. A summary of SAEs and other non-SAEs regardless of causality is located in the Reported Adverse Events module. | Baseline up to 24 weeks plus 30 days post last dose of study drug |
| Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of Necitumumab After a Single Dose | Cycle 1, Day 1; Cohorts 1 and 3: predose, immediately after end of infusion, 0.5, 1, 2, 6, 24, 96 and 168 hours (h) after end of infusion. Cohort 2: predose, immediately after infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion | |
| PK: Cmax of Necitumumab After Multiple Doses | Cmax at steady state (after the last dose of the initial 6-week treatment cycle). | Cycle 1, Day 29; For Cohorts 1, 2 and 3: predose (prior to fourth infusion for Cohorts 1 and 3; prior to third infusion for Cohort 2), immediately after end of infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion |
| PK: Minimum Concentration (Cmin) of Necitumumab After a Single Dose | Cmin is defined as the minimum concentration the drug achieved after administration of first infusion and prior to the administration of second infusion. | Cycle 1; Cohorts 1, 2 and 3: prior to second infusion |
| PK: Cmin of Necitumumab After Multiple Doses | Cmin was calculated prior to the last dose of the initial 6-week treatment cycle. |
| Measure | Description | Time Frame |
|---|---|---|
| Immunogenicity (IK): Number of Participants With Treatment-Emergent Anti-IMC-11F8 Antibodies | Treatment-emergent samples were defined as samples which showed at least 4-fold difference (2 dilution increase) at post-baseline in IK titer over the baseline titer, or participants who tested negative at baseline and positive post-baseline (at titer of ≥1:20). | For Cohorts 1, 2 and 3: Prior to first infusions of Cycles 1, 2, and 4 and at the 30-day follow-up visit (+7 days) after the last dose of study drug |
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Inclusion Criteria:
Exclusion Criteria:
The participant has received chemotherapy or therapeutic radiotherapy within 28 days (6 weeks for nitrosoureas or mitomycin C) prior to entering the study, or the participant has ongoing side effects ≥Grade 2 due to agents administered more than 28 days earlier (except alopecia)
The participant has documented and/or symptomatic brain or leptomeningeal metastases (participants who are clinically stable [no symptoms during the 4 weeks prior to enrollment] with an assessment that no further treatment [radiation, surgical excision, or administration of steroids] is required are permitted to enter the study)
The participant has an uncontrolled intercurrent illness including, but not limited to:
The participant has participated in clinical studies of nonapproved experimental agents or procedures within 4 weeks prior to first dose of study therapy, or within 8 weeks prior to first dose of study therapy for nonapproved monoclonal antibodies
The participant has received any previous treatment with monoclonal antibodies targeting the epidermal growth factor receptor (EGFR). Previous treatment with EGFR tyrosine kinase inhibitors (TKI), approved or nonapproved, is allowed. There must be a time interval of at least 4 weeks between the last EGFR TKI dose and the first dose of IMC-11F8
The participant has acute or subacute intestinal occlusion/obstruction
The participant has a history of inflammatory bowel disease (for example, Crohn's disease, ulcerative colitis) requiring medical intervention in the 3 years prior to study entry
The participant has acute pulmonary disorder, interstitial pneumonia, pulmonary fibrosis, or history thereof
The participant has a known allergy to any of the treatment components, or to monoclonal antibodies or other therapeutic proteins such as fresh frozen plasma, human serum albumin, cytokines, or interleukins. In the event that there is suspicion that the participant may have allergies, the participant should be excluded
The participant, if female, is pregnant (confirmed by urine or serum pregnancy test) or lactating
The participant has known alcohol or drug dependency
The participant is hepatitis B virus (HBV) antigen, hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antibody positive
The participant is assessed as inadequate for the study by the investigator
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| Name | Affiliation | Role |
|---|---|---|
| Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) | Eli Lilly and Company | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| ImClone Investigational Site | Tokyo | 104-0045 | Japan |
Lilly provides access to the individual patient data from studies on approved medicines and indications as defined by the sponsor specific information on ClinicalStudyDataRequest.com.
This access is provided in a timely fashion after the primary publication is accepted. Researchers need to have an approved research proposal submitted through ClinicalStudyDataRequest.com. Access to the data will be provided in a secure data sharing environment after signing a data sharing agreement.
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The study had 3 cohorts and dose escalation in successive cohorts was to occur once all the participants completed 1 cycle of therapy. A completed participant was either a participant who completed the initial 6-week treatment period (Cycle 1) or a participant who discontinued therapy for an IMC-11F8 (Necitumumab) related toxicity during Cycle 1.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1: Necitumumab | Necitumumab 600 milligrams (mg) administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met. |
| FG001 | Cohort 2: Necitumumab | Necitumumab 800 mg administered intravenously every 2 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met. |
| FG002 | Cohort 3: Necitumumab | Necitumumab 800 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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All enrolled participants who received any quantity of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1: Necitumumab | Necitumumab 600 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| 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 1 or More Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) | Data presented are the number of participants who experienced 1 or more TEAEs or SAEs regardless of causality. An adverse event was considered as TEAE if it occurred any time after the administration of the first dose of study drug or up to 30 days after the last dose of study treatment or if it occurred prior to the first dose and worsened while on treatment. A summary of SAEs and other non-SAEs regardless of causality is located in the Reported Adverse Events module. | All participants who received any quantity of study drug. | Posted | Number | participants | Baseline up to 24 weeks plus 30 days post last dose of study drug |
|
Baseline up to 24 weeks plus 30 days post last dose of study drug
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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 | Cohort 1: Necitumumab | Necitumumab 600 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA 12.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Eosinophilia | Blood and lymphatic system disorders | MedDRA 12.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Eli Lilly and Company | 800-545-5979 |
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| ID | Term |
|---|---|
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C527969 | necitumumab |
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| IMC-11F8 | Biological | 800 mg intravenously, every 2 weeks |
|
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| IMC-11F8 | Biological | 800 mg intravenously, Days 1 and 8 every 3 weeks |
|
|
| Cycle 1; Cohorts 1and 3: prior to fourth infusion. Cohort 2: prior to third infusion |
| PK: Area Under the Concentration-Time Curve From Time 0 to Last Time Point [AUC (0-tlast)] of Necitumumab After a Single Dose | Cycle 1, Day 1; Cohorts 1 and 3: predose, immediately after end of infusion, 0.5, 1, 2, 6, 24, 96 and 168 h after end of infusion. Cohort 2: predose, immediately after end of infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion |
| PK: Area Under the Concentration-Time Curve From Time 0 to Infinity [AUC(0-∞)] of Necitumumab After a Single Dose | AUC(0-∞) was calculated only for participants in Cohort 2 as the percentage of AUC extrapolated beyond tlast was greater than 30% for all the remaining participants. | Cycle 1, Day 1; Cohorts 1 and 3: predose, immediately after end of infusion, 0.5, 1, 2, 6, 24, 96 and 168 h after end of infusion. Cohort 2: predose, immediately after end of infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion |
| PK: Area Under the Concentration-Time Curve From Time 0 to 336 h Postdose [AUC(0-336)] of Necitumumab After Multiple Doses | Steady state AUC(0-336) values are reported. | Cycle 1, Day 29; For Cohorts 1, 2 and 3: predose (prior to fourth infusion for Cohorts 1 and 3; prior to third infusion for Cohort 2), immediately after end of infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion |
| PK: Half-Life (t½) of Necitumumab After a Single Dose | The t½ is defined as the time taken for study drug in blood to decrease to half of its concentration. | Cycle 1, Day 1; Cohorts 1 and 3: predose, immediately after end of infusion, 0.5, 1, 2, 6, 24, 96 and 168 h after end of infusion. Cohort 2: predose, immediately after end of infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion |
| PK: t½ of Necitumumab After Multiple Doses | The t½ is defined as the time taken for study drug in blood to decrease to half of its concentration. | Cycle 1, Day 29; For Cohorts 1, 2 and 3: predose (prior to fourth infusion for Cohorts 1 and 3; prior to third infusion for Cohort 2), immediately after end of infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion |
| PK: Clearance (CL) of Necitumumab After a Single Dose | CL is defined as the volume of plasma that is cleared of study drug per unit time. CL was not analyzed for participants in Cohorts 1 and 3 as CL is derived from AUC(0-∞). AUC(0-∞) was calculated only for participants in Cohort 2 as the percentage of AUC extrapolated beyond tlast was greater than 30% for the remaining participants. | Cycle 1, Day 1; Cohorts 1 and 3: predose, immediately after end of infusion, 0.5, 1, 2, 6, 24, 96 and 168 h after end of infusion. Cohort 2: predose, immediately after end of infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion |
| PK: CL of Necitumumab After Multiple Doses | CL is defined as the volume of plasma that is cleared of study drug per unit time. Data did not allow calculation of CL for participants in Cohorts 1 and 3. | Cycle 1, Day 29; For Cohorts 1, 2 and 3: predose (prior to fourth infusion for Cohorts 1 and 3; prior to third infusion for Cohort 2), immediately after end of infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion |
| PK: Steady-State Volume of Distribution (Vss) of Necitumumab After Single Dose | Vss is that amount of plasma in which the study drug needs to be dissolved to attain a steady state drug concentration. Vss was not analyzed for participants in Cohorts 1 and 3 as Vss is derived from AUC (0-∞). AUC(0-∞) was calculated only for participants in Cohort 2 as the percentage of AUC extrapolated beyond tlast was greater than 30% for the remaining participants. | Cycle 1, Day 1; Cohorts 1 and 3: predose, immediately after end of infusion, 0.5, 1, 2, 6, 24, 96 and 168 h after end of infusion. Cohort 2: predose, immediately after end of infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion |
| PK: Vss of Necitumumab After Multiple Doses | Vss is that amount of plasma in which the study drug needs to be dissolved to attain a steady state drug concentration. Data did not allow calculation of Vss for participants in Cohorts 1 and 3. | Cycle 1, Day 29; For Cohorts 1, 2 and 3: predose (prior to fourth infusion for Cohorts 1 and 3; prior to third infusion for Cohort 2), immediately after end of infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion |
| Cohort 2: Necitumumab |
Necitumumab 800 mg administered intravenously every 2 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met. |
| BG002 | Cohort 3: Necitumumab | Necitumumab 800 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met. |
| BG003 | Total | Total of all reporting groups |
| years |
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| Gender | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | participants |
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| Region of Enrollment | Number | participants |
|
| Eastern Cooperative Oncology Group performance status (ECOG PS) | ECOG PS was used to classify participants according to their functional impairment. Score 0 = Fully active, able to carry on all pre-disease performance without restriction. Score 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, for example, light house work, office work. | Number | participants |
|
| OG001 | Cohort 2: Necitumumab | Necitumumab 800 mg administered intravenously every 2 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met. |
| OG002 | Cohort 3: Necitumumab | Necitumumab 800 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met. |
|
|
| Primary | Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of Necitumumab After a Single Dose | All participants who received single dose of study drug and had Cmax values for Day 1 of Cycle 1. | Posted | Geometric Mean | Geometric Coefficient of Variation | micrograms per milliliter (µg/mL) | Cycle 1, Day 1; Cohorts 1 and 3: predose, immediately after end of infusion, 0.5, 1, 2, 6, 24, 96 and 168 hours (h) after end of infusion. Cohort 2: predose, immediately after infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion |
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| Primary | PK: Cmax of Necitumumab After Multiple Doses | Cmax at steady state (after the last dose of the initial 6-week treatment cycle). | All participants who received multiple doses of study drug and had Cmax values for Day 29 of Cycle 1. | Posted | Geometric Mean | Geometric Coefficient of Variation | µg/mL | Cycle 1, Day 29; For Cohorts 1, 2 and 3: predose (prior to fourth infusion for Cohorts 1 and 3; prior to third infusion for Cohort 2), immediately after end of infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion |
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| Primary | PK: Minimum Concentration (Cmin) of Necitumumab After a Single Dose | Cmin is defined as the minimum concentration the drug achieved after administration of first infusion and prior to the administration of second infusion. | All participants who received single dose of study drug and had Cmin serum concentrations analyzed prior to administration of second dose. | Posted | Geometric Mean | Geometric Coefficient of Variation | µg/mL | Cycle 1; Cohorts 1, 2 and 3: prior to second infusion |
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| Primary | PK: Cmin of Necitumumab After Multiple Doses | Cmin was calculated prior to the last dose of the initial 6-week treatment cycle. | All participants who received multiple doses of study drug and had Cmin serum concentrations prior to last dose of Cycle 1. | Posted | Geometric Mean | Geometric Coefficient of Variation | µg/mL | Cycle 1; Cohorts 1and 3: prior to fourth infusion. Cohort 2: prior to third infusion |
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| Primary | PK: Area Under the Concentration-Time Curve From Time 0 to Last Time Point [AUC (0-tlast)] of Necitumumab After a Single Dose | All participants who received single dose of study drug and had evaluable AUC(0-∞) values for Day 1 of Cycle 1. | Posted | Geometric Mean | Geometric Coefficient of Variation | micrograms*hour/milliliter (µg*h/mL) | Cycle 1, Day 1; Cohorts 1 and 3: predose, immediately after end of infusion, 0.5, 1, 2, 6, 24, 96 and 168 h after end of infusion. Cohort 2: predose, immediately after end of infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion |
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| Primary | PK: Area Under the Concentration-Time Curve From Time 0 to Infinity [AUC(0-∞)] of Necitumumab After a Single Dose | AUC(0-∞) was calculated only for participants in Cohort 2 as the percentage of AUC extrapolated beyond tlast was greater than 30% for all the remaining participants. | All participants who received single dose of study drug and had evaluable AUC(0-∞) values for Day 1 of Cycle 1. No participant of Cohorts 1 and 3 were analyzed for AUC(0-∞) on Day 1 of Cycle 1, due to fraction of data outside tlast >30% | Posted | Geometric Mean | Geometric Coefficient of Variation | µg*h/mL | Cycle 1, Day 1; Cohorts 1 and 3: predose, immediately after end of infusion, 0.5, 1, 2, 6, 24, 96 and 168 h after end of infusion. Cohort 2: predose, immediately after end of infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion |
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| Secondary | Immunogenicity (IK): Number of Participants With Treatment-Emergent Anti-IMC-11F8 Antibodies | Treatment-emergent samples were defined as samples which showed at least 4-fold difference (2 dilution increase) at post-baseline in IK titer over the baseline titer, or participants who tested negative at baseline and positive post-baseline (at titer of ≥1:20). | All participants who received any quantity of study drug. | Posted | Number | participants | For Cohorts 1, 2 and 3: Prior to first infusions of Cycles 1, 2, and 4 and at the 30-day follow-up visit (+7 days) after the last dose of study drug |
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| Primary | PK: Area Under the Concentration-Time Curve From Time 0 to 336 h Postdose [AUC(0-336)] of Necitumumab After Multiple Doses | Steady state AUC(0-336) values are reported. | All the participants who received multiple doses of study drug and had AUC(0-336) values for Day 29 of Cycle 1. | Posted | Geometric Mean | Geometric Coefficient of Variation | µg*h/mL | Cycle 1, Day 29; For Cohorts 1, 2 and 3: predose (prior to fourth infusion for Cohorts 1 and 3; prior to third infusion for Cohort 2), immediately after end of infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion |
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| Primary | PK: Half-Life (t½) of Necitumumab After a Single Dose | The t½ is defined as the time taken for study drug in blood to decrease to half of its concentration. | All participants who received single dose of study drug and had t½ values for Day 1 of Cycle 1. | Posted | Geometric Mean | Geometric Coefficient of Variation | h | Cycle 1, Day 1; Cohorts 1 and 3: predose, immediately after end of infusion, 0.5, 1, 2, 6, 24, 96 and 168 h after end of infusion. Cohort 2: predose, immediately after end of infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion |
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| Primary | PK: t½ of Necitumumab After Multiple Doses | The t½ is defined as the time taken for study drug in blood to decrease to half of its concentration. | All the participants who received multiple doses of study drug and had t½ values for Day 29 of Cycle 1. | Posted | Geometric Mean | Geometric Coefficient of Variation | h | Cycle 1, Day 29; For Cohorts 1, 2 and 3: predose (prior to fourth infusion for Cohorts 1 and 3; prior to third infusion for Cohort 2), immediately after end of infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion |
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| Primary | PK: Clearance (CL) of Necitumumab After a Single Dose | CL is defined as the volume of plasma that is cleared of study drug per unit time. CL was not analyzed for participants in Cohorts 1 and 3 as CL is derived from AUC(0-∞). AUC(0-∞) was calculated only for participants in Cohort 2 as the percentage of AUC extrapolated beyond tlast was greater than 30% for the remaining participants. | All the participants who received single dose of study drug and had CL values for Day 1 of Cycle 1. No participant of Cohorts 1 and 3 were analyzed for CL on Day 1 of Cycle 1, due to fraction of data outside tlast >30% | Posted | Geometric Mean | Geometric Coefficient of Variation | milliliters per hour (mL/h) | Cycle 1, Day 1; Cohorts 1 and 3: predose, immediately after end of infusion, 0.5, 1, 2, 6, 24, 96 and 168 h after end of infusion. Cohort 2: predose, immediately after end of infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion |
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| Primary | PK: CL of Necitumumab After Multiple Doses | CL is defined as the volume of plasma that is cleared of study drug per unit time. Data did not allow calculation of CL for participants in Cohorts 1 and 3. | All the participants who received multiple doses of study drug and had CL values for Day 29 of Cycle 1. CL of necitumumab was not assessed for participants in Cohorts 1 and 3, due to the irregular dosing regimen. | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/h | Cycle 1, Day 29; For Cohorts 1, 2 and 3: predose (prior to fourth infusion for Cohorts 1 and 3; prior to third infusion for Cohort 2), immediately after end of infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion |
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| Primary | PK: Steady-State Volume of Distribution (Vss) of Necitumumab After Single Dose | Vss is that amount of plasma in which the study drug needs to be dissolved to attain a steady state drug concentration. Vss was not analyzed for participants in Cohorts 1 and 3 as Vss is derived from AUC (0-∞). AUC(0-∞) was calculated only for participants in Cohort 2 as the percentage of AUC extrapolated beyond tlast was greater than 30% for the remaining participants. | All participants who received single dose of study drug and had Vss values for Day 1 of Cycle 1. Vss of necitumumab was not assessed for participants in Cohorts 1 and 3, due to the irregular dosing regimen. | Posted | Geometric Mean | Geometric Coefficient of Variation | milliliters (mL) | Cycle 1, Day 1; Cohorts 1 and 3: predose, immediately after end of infusion, 0.5, 1, 2, 6, 24, 96 and 168 h after end of infusion. Cohort 2: predose, immediately after end of infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion |
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| Primary | PK: Vss of Necitumumab After Multiple Doses | Vss is that amount of plasma in which the study drug needs to be dissolved to attain a steady state drug concentration. Data did not allow calculation of Vss for participants in Cohorts 1 and 3. | All participants who received multiple doses of study drug and had Vss values for Day 29 of Cycle 1. Vss of necitumumab was not assessed for participants in Cohorts 1 and 3, due to the irregular dosing regimen. | Posted | Geometric Mean | Geometric Coefficient of Variation | mL | Cycle 1, Day 29; For Cohorts 1, 2 and 3: predose (prior to fourth infusion for Cohorts 1 and 3; prior to third infusion for Cohort 2), immediately after end of infusion, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 h after end of infusion |
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| 1 |
| 3 |
| 3 |
| 3 |
| EG001 | Cohort 2: Necitumumab | Necitumumab 800 mg administered intravenously every 2 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met. | 0 | 6 | 6 | 6 |
| EG002 | Cohort 3: Necitumumab | Necitumumab 800 mg administered intravenously on Days 1 and 8 every 3 weeks of a 6-week cycle. After Cycle 1, participants showing objective response or stable disease were to receive necitumumab at same dose and schedule until disease progression or other withdrawal criteria were met. | 1 | 6 | 6 | 6 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Oropharyngeal discomfort | Respiratory, thoracic and mediastinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | MedDRA 12.0 | Systematic Assessment |
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| Palpitations | Cardiac disorders | MedDRA 12.0 | Systematic Assessment |
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| Sinus bradycardia | Cardiac disorders | MedDRA 12.0 | Systematic Assessment |
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| Vertigo | Ear and labyrinth disorders | MedDRA 12.0 | Systematic Assessment |
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| Dry eye | Eye disorders | MedDRA 12.0 | Systematic Assessment |
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| Eye discharge | Eye disorders | MedDRA 12.0 | Systematic Assessment |
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| Abdominal discomfort | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Anal haemorrhage | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Cheilitis | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Dysphagia | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Gingivitis | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Lip dry | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Stomatitis | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Face oedema | General disorders | MedDRA 12.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 12.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 12.0 | Systematic Assessment |
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| Candidiasis | Infections and infestations | MedDRA 12.0 | Systematic Assessment |
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| Cystitis | Infections and infestations | MedDRA 12.0 | Systematic Assessment |
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| Enterocolitis infectious | Infections and infestations | MedDRA 12.0 | Systematic Assessment |
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| Paronychia | Infections and infestations | MedDRA 12.0 | Systematic Assessment |
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| Pharyngitis | Infections and infestations | MedDRA 12.0 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA 12.0 | Systematic Assessment |
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| Arthropod sting | Injury, poisoning and procedural complications | MedDRA 12.0 | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA 12.0 | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA 12.0 | Systematic Assessment |
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| Blood alkaline phosphatase increased | Investigations | MedDRA 12.0 | Systematic Assessment |
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| Blood amylase increased | Investigations | MedDRA 12.0 | Systematic Assessment |
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| Blood bilirubin increased | Investigations | MedDRA 12.0 | Systematic Assessment |
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| Blood potassium increased | Investigations | MedDRA 12.0 | Systematic Assessment |
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| Glucose urine present | Investigations | MedDRA 12.0 | Systematic Assessment |
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| Weight decreased | Investigations | MedDRA 12.0 | Systematic Assessment |
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| White blood cell count decreased | Investigations | MedDRA 12.0 | Systematic Assessment |
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| Anorexia | Metabolism and nutrition disorders | MedDRA 12.0 | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA 12.0 | Systematic Assessment |
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| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 12.0 | Systematic Assessment |
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| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 12.0 | Systematic Assessment |
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| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 12.0 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 12.0 | Systematic Assessment |
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| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 12.0 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 12.0 | Systematic Assessment |
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| Akathisia | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
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| Dysarthria | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
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| Myoclonus | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA 12.0 | Systematic Assessment |
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| Proteinuria | Renal and urinary disorders | MedDRA 12.0 | Systematic Assessment |
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| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Nasal discomfort | Respiratory, thoracic and mediastinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Oropharyngeal discomfort | Respiratory, thoracic and mediastinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Acne | Skin and subcutaneous tissue disorders | MedDRA 12.0 | Systematic Assessment |
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| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 12.0 | Systematic Assessment |
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| Nail disorder | Skin and subcutaneous tissue disorders | MedDRA 12.0 | Systematic Assessment |
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| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA 12.0 | Systematic Assessment |
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| Periorbital oedema | Skin and subcutaneous tissue disorders | MedDRA 12.0 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 12.0 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 12.0 | Systematic Assessment |
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| Rash generalised | Skin and subcutaneous tissue disorders | MedDRA 12.0 | Systematic Assessment |
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| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 12.0 | Systematic Assessment |
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| Flushing | Vascular disorders | MedDRA 12.0 | Systematic Assessment |
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| Hot flush | Vascular disorders | MedDRA 12.0 | Systematic Assessment |
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Investigators agreed to delay independently publishing or disclosing data, findings or conclusions from the study except as part of a multi-center publication. Upon study completion or if the draft publication is not produced within approximately 6 months of the final report of the study results, investigators may independently publish, subject to confidential information review/redaction by sponsor. The sponsor may request publication delay up to 90 days to seek patent protection.
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