Advanced Solid Tumors
Conditions
Keywords
Solid tumor, recombinant human IgG1, MAB, monoclonal antibody, VEGFR 2, human vascular endothelial growth factor receptor 2
Brief summary
This trial is testing the investigational drug IMC-1121B administered to Japanese participants with advanced solid tumors who have not responded to standard therapy or for whom no standard therapy is available. The rationale for performing this trial is to establish the safety profile and the pharmacokinetics of IMC-1121B.
Detailed description
This single center, open-label, single-arm, Phase 1 study will enroll approximately 15 to 18 participants. The actual size will vary depending on the dose-limiting toxicities (DLTs) observed and the resultant sizes of the cohorts. Participants will receive IMC-1121B, administered intravenously, once every 2 or 3 weeks for 6 weeks (one cycle). After one cycle of treatment, participants who have an objective response or stable disease may continue to receive IMC-1121B at the same dose and schedule until disease progression or other withdrawal criteria are met. A minimum of three participants will be enrolled in each cohort. Dose escalation in successive cohorts will occur once all participants complete one 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-1121B related toxicity during Cycle 1. Participants who do not complete the first 6 weeks of treatment for reasons other than an IMC-1121B -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.
Interventions
BIOLOGICALIMC-1121B
Cycle 1: Upon completion of enrollment criteria confirmed at screening, the first dose of study medication should be administered within 7 days. The infusion will be planned every 2 weeks or every 3 weeks on the same day of the week of the first infusion. Dose escalation to Cohort 2 may occur in the absence of a dose-limiting toxicity (DLT) in the first three participants treated in Cohort 1 during the initial 6-week dosing period (Cycle 1). The same procedure will be followed for dose escalation from Cohort 2 to Cohort 3. If 1 of 3 participants in any cohort experiences a DLT in the first 6 weeks (Cycle 1), 3 additional participants will be enrolled in that cohort. Dose escalation to the next cohort may occur if less that 2 of 6 participants experience a DLT during Cycle 1.
Sponsors
Parexel
Eli Lilly and Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Solid tumor participant who was been histopathologically or cytologically documented. * Advanced primary or recurrent solid tumors participant who has not responded to standard therapy or no standard therapy is available. * The participant has measurable or nonmeasurable lesions according to Response Evaluation Criteria in Solid Tumors (RECIST). * The participant has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0-1 at study entry. * The participant is able to provide written informed consent. * The participant is age 20 years or older. * The participant has a life expectancy of \> 3 months. * The participant has adequate hematologic function, as defined by: * An absolute neutrophil count (ANC) \> 1500/cubic millimeter (mm³) or /microliter (µL) * A hemoglobin level \> 10 grams/deciliter (g/dL) * A platelet count \> 100,000/mm³ or /µL * The participant has adequate hepatic function, as defined by: * A total bilirubin level \< 1.8 milligrams/deciliter (mg/dL) * Aspartate transaminase (AST) levels \< 86 International Units/liter (IU/L) * Alanine transaminase (ALT) levels ≤ 86 IU/L * The participant has adequate renal function, as defined by: * Serum creatinine level ≤ 1.5 mg/dL, or * Calculated serum creatinine clearance (Cockcroft-Gault) ≥ 60 milliliters/minute (mL/min) * The participant's urinary protein is 0 on dipstick or 1+ but participant does not have edema nor serum albumin \< lower level of normal (LLN). * The participant has adequate coagulation function, as defined by international normalized ratio (INR) ≤ 1.5. * The participant agrees to use adequate contraception during the study period and for 12 weeks after the last dose of study treatment.
Exclusion criteria
* The participant has had chemotherapy or therapeutic radiotherapy within 28 days (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or participant has ongoing side effects ≥ Grade 2 due to agents administered more than 28 days earlier. * The participant has obvious evidence of intratumor cavitation. * The participant has undergone major surgery (example, laparotomy, thoracotomy, removal of organ\[s\]) within 28 days prior to study entry, or subcutaneous venous access device placement within 7 days prior to study entry. * The participant has a history of postoperative bleeding complications or wound complications from a surgical procedure. * The participant has elective or planned surgery to be conducted during the trial. * The participant has documented and/or symptomatic brain or leptomeningeal metastases. (Participants who are clinically stable \[no symptoms during 4 weeks prior to the enrollment\] with an assessment that no further treatment \[radiation, surgical excision, and administration of steroids\] is required, are permitted to enter the study.) * The participant has uncontrolled intercurrent illness including, but not limited to: * Thrombotic or hemorrhagic disorders * Hemoptysis (approximately one-half of a teaspoon) * Ongoing or active infection requiring systemic antibiotic treatment * Congestive heart failure (Class III or IV of the New York Heart Association classification for heart disease) * Angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months * Uncontrolled hypertension (systolic blood pressure \> 150 millimeters of mercury (mmHg), diastolic blood pressure \> 95 mm Hg) * Cardiac arrhythmia requires treatment \[National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0 (NCI-CTCAE v 3.0), Grade 3\], or asymptomatic sustained ventricular tachycardia) * Peripheral neuropathy of any etiology ≥ Grade 2 (NCI-CTCAE v 3.0) * The participant has participated in clinical studies of non-approved experimental agents or procedures within 4 weeks prior to study entry for small molecules, or 8 weeks prior to study entry for non-approved monoclonal antibodies. * The participant, if female, is pregnant (confirmed by urine or serum pregnancy test) or lactating.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| IMC-1121B Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohort 3 During Cycles 3 to 5 | Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour post-dose | Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, Vss could not be calculated. |
| Number of Participants With Drug-Related Adverse Events | Baseline to study completion up to 48 weeks | Data presented are the number of participants who experienced adverse events (AE) of any grade, AE of Grade ≥3 based on National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0 (NCI-CTCAE v 3.0), serious adverse events (SAE) and AE resulting in death that was considered to be related to IMC-1121B (ramucirumab). A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module. |
| IMC-1121B Pharmacokinetics: Maximum Serum Concentration (Cmax) - Cohorts 1 and 2 During Cycles 1 and 2 | Day 1 to Day 15 of Cycles 1 and 2 of a 6-week cycle | — |
| IMC-1121B Pharmacokinetics: Maximum Serum Concentration (Cmax) - Cohorts 1 and 2 During Cycles 3 to 5 | Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose | Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, Cmax could not be calculated. |
| IMC-1121B Pharmacokinetics: Area Under the Concentration (AUC) Versus Time Curve - Cohorts 1 and 2 During Cycles 1 and 2 | Day 1 to Day 15 of Cycles 1 and 2 of a 6-week cycle | AUC for Cycle 1 is AUC from time zero to infinity \[AUC(0-∞)\] and for Cycle 2 is AUC over a dosing interval (AUCτ). |
| IMC-1121B Pharmacokinetics: Area Under the Concentration (AUC) - Cohorts 1 and 2 During Cycles 3 to 5 | Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose | Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, AUC could not be calculated. |
| IMC-1121B Pharmacokinetics: Half-Life (t1/2) - Cohorts 1 and 2 During Cycles 1 and 2 | Day 1 to Day 15 of Cycles 1 and 2 of a 6-week cycle | — |
| IMC-1121B Pharmacokinetics: Half-Life (t 1/2) - Cohorts 1 and 2 During Cycles 3 to 5 | Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose | Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, t1/2 could not be calculated. |
| IMC-1121B Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohorts 1 and 2 During Cycles 1 and 2 | Day 1 to Day 15 of Cycles 1 and 2 of a 6-week cycle | — |
| IMC-1121B Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohorts 1 and 2 During Cycles 3 to 5 | Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose | Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, Vss could not be calculated. |
| IMC-1121B Pharmacokinetics: Maximum Serum Concentration (Cmax) - Cohort 3 During Cycles 1 and 2 | Day 1 to Day 22 of Cycles 1 and 2 of a 6-week cycle | — |
| IMC-1121B Pharmacokinetics: Maximum Serum Concentration (Cmax) - Cohort 3 During Cycles 3 to 5 | Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose | Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, Cmax could not be calculated. |
| IMC-1121B Pharmacokinetics: Area Under the Concentration (AUC) - Cohort 3 During Cycles 1 and 2 | Day 1 to Day 22 of Cycles 1 and 2 of a 6-week cycle | AUC for Cycle 1 is AUC from time zero to infinity \[AUC(0-∞)\] and for Cycle 2 is AUC over a dosing interval (AUCτ). |
| IMC-1121B Pharmacokinetics - Area Under the Concentration (AUC) - Cohort 3 During Cycles 3 to 5 | Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose | Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, AUC could not be calculated. |
| IMC-1121B Pharmacokinetics: Half-Life (t1/2) - Cohort 3 During Cycles 1 and 2 | Day 1 to Day 22 of Cycles 1 and 2 of a 6-week cycle | — |
| IMC-1121B Pharmacokinetics: Half-Life (t 1/2) - Cohort 3 During Cycles 3 to 5 | Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose | Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, t1/2 could not be calculated. |
| IMC-1121B Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohort 3 During Cycles 1 and 2 | Day 1 and Day 22 of Cycles 1 and 2 of a 6-week cycle | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Screen for the Development of Circulating Antibodies Against IMC-1121B (Immunogenicity) | Baseline to study completion up to 48 weeks | Data presented are the number of participants with treatment emergent antibody positive. |
Countries
Japan
Participant flow
Pre-assignment details
A participant was considered to have completed the study if he or she completed the initial 6-week treatment period (Cycle 1) or if he or she discontinued therapy because of an IMC-1121B (ramucirumab)-related toxicity during Cycle 1.
Participants by arm
| Arm | Count |
|---|---|
| IMC-1121B 6 mg/kg (Cohort 1) 6 milligrams/kilogram (mg/kg) IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 2 weeks for 6 weeks (1 cycle).
After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met. | 3 |
| IMC-1121B 8 mg/kg (Cohort 2) 8 mg/kg IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 2 weeks for 6 weeks (1 cycle).
After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met. | 6 |
| IMC-1121B 10 mg/kg (Cohort 3) 10 mg/kg IMC-1121B (ramucirumab) based on participant's body weight administered intravenously over 1 hour on Day 1 every 3 weeks for 6 weeks (1 cycle).
After 1 cycle of treatment, participants who had an objective response or stable disease were permitted to receive IMC-1121B (ramucirumab) at the same dose and schedule until disease progression or unacceptable toxicity occurred, or another withdrawal criterion was met. | 6 |
| Total | 15 |
Baseline characteristics
| Characteristic | IMC-1121B 6 mg/kg (Cohort 1) | IMC-1121B 8 mg/kg (Cohort 2) | IMC-1121B 10 mg/kg (Cohort 3) | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 6 Participants | 4 Participants | 13 Participants |
| Race/Ethnicity, Customized Asian | 3 participants | 6 participants | 6 participants | 15 participants |
| Region of Enrollment Japan | 3 participants | 6 participants | 6 participants | 15 participants |
| Sex: Female, Male Female | 1 Participants | 5 Participants | 3 Participants | 9 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 3 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 6 / 6 | 6 / 6 |
| serious Total, serious adverse events | 1 / 3 | 2 / 6 | 2 / 6 |
Outcome results
Primary
IMC-1121B Pharmacokinetics: Area Under the Concentration (AUC) - Cohort 3 During Cycles 1 and 2
AUC for Cycle 1 is AUC from time zero to infinity \[AUC(0-∞)\] and for Cycle 2 is AUC over a dosing interval (AUCτ).
Time frame: Day 1 to Day 22 of Cycles 1 and 2 of a 6-week cycle
Population: All participants in Cohort 3 who received study drug and had sufficient pharmacokinetics data to calculate AUC(0-∞) for Cycle 1 and AUCτ for Cycle 2.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IMC-1121B 6 mg/kg (Cohort 1) | IMC-1121B Pharmacokinetics: Area Under the Concentration (AUC) - Cohort 3 During Cycles 1 and 2 | Cycle 1 - AUC(0-∞) | 61600 micrograms*hour/milliliter (mcg*h/mL) | Standard Deviation 17100 |
| IMC-1121B 6 mg/kg (Cohort 1) | IMC-1121B Pharmacokinetics: Area Under the Concentration (AUC) - Cohort 3 During Cycles 1 and 2 | Cycle 2 - AUCτ | 103000 micrograms*hour/milliliter (mcg*h/mL) | Standard Deviation 26200 |
Primary
IMC-1121B Pharmacokinetics - Area Under the Concentration (AUC) - Cohort 3 During Cycles 3 to 5
Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, AUC could not be calculated.
Time frame: Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose
Population: Zero participants were analyzed due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5.
Primary
IMC-1121B Pharmacokinetics: Area Under the Concentration (AUC) - Cohorts 1 and 2 During Cycles 3 to 5
Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, AUC could not be calculated.
Time frame: Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose
Population: Zero participants were analyzed due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5.
Primary
IMC-1121B Pharmacokinetics: Area Under the Concentration (AUC) Versus Time Curve - Cohorts 1 and 2 During Cycles 1 and 2
AUC for Cycle 1 is AUC from time zero to infinity \[AUC(0-∞)\] and for Cycle 2 is AUC over a dosing interval (AUCτ).
Time frame: Day 1 to Day 15 of Cycles 1 and 2 of a 6-week cycle
Population: All participants in Cohorts 1 and 2 who received study drug and had sufficient pharmacokinetics data to calculate AUC(0-∞) for Cycle 1 and AUCτ for Cycle 2.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IMC-1121B 6 mg/kg (Cohort 1) | IMC-1121B Pharmacokinetics: Area Under the Concentration (AUC) Versus Time Curve - Cohorts 1 and 2 During Cycles 1 and 2 | Cycle 1 - AUC(0-∞) (n=1, 1) | 36900 micrograms*hour/milliliter (mcg*h/mL) | — |
| IMC-1121B 6 mg/kg (Cohort 1) | IMC-1121B Pharmacokinetics: Area Under the Concentration (AUC) Versus Time Curve - Cohorts 1 and 2 During Cycles 1 and 2 | Cycle 2 - AUCτ (n=1, 2) | 56400 micrograms*hour/milliliter (mcg*h/mL) | — |
| IMC-1121B 8 mg/kg (Cohort 2) | IMC-1121B Pharmacokinetics: Area Under the Concentration (AUC) Versus Time Curve - Cohorts 1 and 2 During Cycles 1 and 2 | Cycle 1 - AUC(0-∞) (n=1, 1) | 73800 micrograms*hour/milliliter (mcg*h/mL) | — |
| IMC-1121B 8 mg/kg (Cohort 2) | IMC-1121B Pharmacokinetics: Area Under the Concentration (AUC) Versus Time Curve - Cohorts 1 and 2 During Cycles 1 and 2 | Cycle 2 - AUCτ (n=1, 2) | 102000 micrograms*hour/milliliter (mcg*h/mL) | Standard Deviation 10400 |
Primary
IMC-1121B Pharmacokinetics: Half-Life (t1/2) - Cohort 3 During Cycles 1 and 2
Time frame: Day 1 to Day 22 of Cycles 1 and 2 of a 6-week cycle
Population: All participants in Cohort 3 who received study drug and had sufficient pharmacokinetics data to calculate t1/2 for Cycles 1 and 2.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| IMC-1121B 6 mg/kg (Cohort 1) | IMC-1121B Pharmacokinetics: Half-Life (t1/2) - Cohort 3 During Cycles 1 and 2 | Cycle 1 | 234 hours |
| IMC-1121B 6 mg/kg (Cohort 1) | IMC-1121B Pharmacokinetics: Half-Life (t1/2) - Cohort 3 During Cycles 1 and 2 | Cycle 2 (n=1) | 329 hours |
Primary
IMC-1121B Pharmacokinetics: Half-Life (t 1/2) - Cohort 3 During Cycles 3 to 5
Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, t1/2 could not be calculated.
Time frame: Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose
Population: Zero participants were analyzed due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5.
Primary
IMC-1121B Pharmacokinetics: Half-Life (t1/2) - Cohorts 1 and 2 During Cycles 1 and 2
Time frame: Day 1 to Day 15 of Cycles 1 and 2 of a 6-week cycle
Population: All participants in Cohorts 1 and 2 who received study drug and had sufficient pharmacokinetics data to calculate t1/2 for Cycles 1 and 2.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| IMC-1121B 6 mg/kg (Cohort 1) | IMC-1121B Pharmacokinetics: Half-Life (t1/2) - Cohorts 1 and 2 During Cycles 1 and 2 | Cycle 1 | 158 hours |
| IMC-1121B 6 mg/kg (Cohort 1) | IMC-1121B Pharmacokinetics: Half-Life (t1/2) - Cohorts 1 and 2 During Cycles 1 and 2 | Cycle 2 (n=0, 0) | NA hours |
| IMC-1121B 8 mg/kg (Cohort 2) | IMC-1121B Pharmacokinetics: Half-Life (t1/2) - Cohorts 1 and 2 During Cycles 1 and 2 | Cycle 1 | 165 hours |
| IMC-1121B 8 mg/kg (Cohort 2) | IMC-1121B Pharmacokinetics: Half-Life (t1/2) - Cohorts 1 and 2 During Cycles 1 and 2 | Cycle 2 (n=0, 0) | NA hours |
Primary
IMC-1121B Pharmacokinetics: Half-Life (t 1/2) - Cohorts 1 and 2 During Cycles 3 to 5
Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, t1/2 could not be calculated.
Time frame: Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose
Population: Zero participants were analyzed due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5.
Primary
IMC-1121B Pharmacokinetics: Maximum Serum Concentration (Cmax) - Cohort 3 During Cycles 1 and 2
Time frame: Day 1 to Day 22 of Cycles 1 and 2 of a 6-week cycle
Population: All participants in Cohort 3 who received study drug and had sufficient pharmacokinetics data to calculate Cmax for Cycles 1 and 2.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IMC-1121B 6 mg/kg (Cohort 1) | IMC-1121B Pharmacokinetics: Maximum Serum Concentration (Cmax) - Cohort 3 During Cycles 1 and 2 | Cycle 1 | 493 micrograms/milliliter (mcg/mL) | Standard Deviation 122 |
| IMC-1121B 6 mg/kg (Cohort 1) | IMC-1121B Pharmacokinetics: Maximum Serum Concentration (Cmax) - Cohort 3 During Cycles 1 and 2 | Cycle 2 (n=2) | 793 micrograms/milliliter (mcg/mL) | Standard Deviation 367 |
Primary
IMC-1121B Pharmacokinetics: Maximum Serum Concentration (Cmax) - Cohort 3 During Cycles 3 to 5
Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, Cmax could not be calculated.
Time frame: Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose
Population: Zero participants were analyzed due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5.
Primary
IMC-1121B Pharmacokinetics: Maximum Serum Concentration (Cmax) - Cohorts 1 and 2 During Cycles 1 and 2
Time frame: Day 1 to Day 15 of Cycles 1 and 2 of a 6-week cycle
Population: All participants in Cohorts 1 and 2 who received study drug and had sufficient pharmacokinetics data to calculate Cmax for Cycles 1 and 2.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IMC-1121B 6 mg/kg (Cohort 1) | IMC-1121B Pharmacokinetics: Maximum Serum Concentration (Cmax) - Cohorts 1 and 2 During Cycles 1 and 2 | Cycle 1 | 284 micrograms/milliliter (mcg/mL) | Standard Deviation 63.7 |
| IMC-1121B 6 mg/kg (Cohort 1) | IMC-1121B Pharmacokinetics: Maximum Serum Concentration (Cmax) - Cohorts 1 and 2 During Cycles 1 and 2 | Cycle 2 (n=1, 2) | 352 micrograms/milliliter (mcg/mL) | — |
| IMC-1121B 8 mg/kg (Cohort 2) | IMC-1121B Pharmacokinetics: Maximum Serum Concentration (Cmax) - Cohorts 1 and 2 During Cycles 1 and 2 | Cycle 1 | 371 micrograms/milliliter (mcg/mL) | Standard Deviation 113 |
| IMC-1121B 8 mg/kg (Cohort 2) | IMC-1121B Pharmacokinetics: Maximum Serum Concentration (Cmax) - Cohorts 1 and 2 During Cycles 1 and 2 | Cycle 2 (n=1, 2) | 694 micrograms/milliliter (mcg/mL) | Standard Deviation 123 |
Primary
IMC-1121B Pharmacokinetics: Maximum Serum Concentration (Cmax) - Cohorts 1 and 2 During Cycles 3 to 5
Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, Cmax could not be calculated.
Time frame: Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose
Population: Zero participants were analyzed due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5.
Primary
IMC-1121B Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohort 3 During Cycles 1 and 2
Time frame: Day 1 and Day 22 of Cycles 1 and 2 of a 6-week cycle
Population: All participants in Cohort 3 who received study drug and had sufficient pharmacokinetics data to calculate Vss for Cycle 1. Vss is not calculated for multiple doses, therefore zero participants were analyzed for Cycle 2.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IMC-1121B 6 mg/kg (Cohort 1) | IMC-1121B Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohort 3 During Cycles 1 and 2 | Cycle 1 | 40.7 milliliters/kilogram (mL/kg) | Standard Deviation 1.22 |
| IMC-1121B 6 mg/kg (Cohort 1) | IMC-1121B Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohort 3 During Cycles 1 and 2 | Cycle 2 (n=0) | NA milliliters/kilogram (mL/kg) | — |
Primary
IMC-1121B Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohort 3 During Cycles 3 to 5
Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, Vss could not be calculated.
Time frame: Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour post-dose
Population: Zero participants were analyzed due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5.
Primary
IMC-1121B Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohorts 1 and 2 During Cycles 1 and 2
Time frame: Day 1 to Day 15 of Cycles 1 and 2 of a 6-week cycle
Population: All participants in Cohorts 1 and 2 who received study drug and had sufficient pharmacokinetics data to calculate Vss for Cycle 1. Vss is not calculated for multiple doses, therefore zero participants were analyzed for Cycle 2.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| IMC-1121B 6 mg/kg (Cohort 1) | IMC-1121B Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohorts 1 and 2 During Cycles 1 and 2 | Cycle 1 | 25.0 milliliters/kilogram (mL/kg) |
| IMC-1121B 6 mg/kg (Cohort 1) | IMC-1121B Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohorts 1 and 2 During Cycles 1 and 2 | Cycle 2 (n=0, 0) | NA milliliters/kilogram (mL/kg) |
| IMC-1121B 8 mg/kg (Cohort 2) | IMC-1121B Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohorts 1 and 2 During Cycles 1 and 2 | Cycle 1 | 21.4 milliliters/kilogram (mL/kg) |
| IMC-1121B 8 mg/kg (Cohort 2) | IMC-1121B Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohorts 1 and 2 During Cycles 1 and 2 | Cycle 2 (n=0, 0) | NA milliliters/kilogram (mL/kg) |
Primary
IMC-1121B Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohorts 1 and 2 During Cycles 3 to 5
Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, Vss could not be calculated.
Time frame: Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdose
Population: Zero participants were analyzed due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5.
Primary
Number of Participants With Drug-Related Adverse Events
Data presented are the number of participants who experienced adverse events (AE) of any grade, AE of Grade ≥3 based on National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0 (NCI-CTCAE v 3.0), serious adverse events (SAE) and AE resulting in death that was considered to be related to IMC-1121B (ramucirumab). A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module.
Time frame: Baseline to study completion up to 48 weeks
Population: All participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IMC-1121B 6 mg/kg (Cohort 1) | Number of Participants With Drug-Related Adverse Events | SAE | 0 participants |
| IMC-1121B 6 mg/kg (Cohort 1) | Number of Participants With Drug-Related Adverse Events | AE resulting in death | 0 participants |
| IMC-1121B 6 mg/kg (Cohort 1) | Number of Participants With Drug-Related Adverse Events | AE of any grade | 3 participants |
| IMC-1121B 6 mg/kg (Cohort 1) | Number of Participants With Drug-Related Adverse Events | AE of Grade ≥3 | 0 participants |
| IMC-1121B 8 mg/kg (Cohort 2) | Number of Participants With Drug-Related Adverse Events | SAE | 0 participants |
| IMC-1121B 8 mg/kg (Cohort 2) | Number of Participants With Drug-Related Adverse Events | AE of Grade ≥3 | 0 participants |
| IMC-1121B 8 mg/kg (Cohort 2) | Number of Participants With Drug-Related Adverse Events | AE resulting in death | 0 participants |
| IMC-1121B 8 mg/kg (Cohort 2) | Number of Participants With Drug-Related Adverse Events | AE of any grade | 6 participants |
| IMC-1121B 10 mg/kg (Cohort 3) | Number of Participants With Drug-Related Adverse Events | AE resulting in death | 0 participants |
| IMC-1121B 10 mg/kg (Cohort 3) | Number of Participants With Drug-Related Adverse Events | AE of any grade | 6 participants |
| IMC-1121B 10 mg/kg (Cohort 3) | Number of Participants With Drug-Related Adverse Events | AE of Grade ≥3 | 1 participants |
| IMC-1121B 10 mg/kg (Cohort 3) | Number of Participants With Drug-Related Adverse Events | SAE | 1 participants |
Secondary
Screen for the Development of Circulating Antibodies Against IMC-1121B (Immunogenicity)
Data presented are the number of participants with treatment emergent antibody positive.
Time frame: Baseline to study completion up to 48 weeks
Population: All participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IMC-1121B 6 mg/kg (Cohort 1) | Screen for the Development of Circulating Antibodies Against IMC-1121B (Immunogenicity) | 0 participants |
| IMC-1121B 8 mg/kg (Cohort 2) | Screen for the Development of Circulating Antibodies Against IMC-1121B (Immunogenicity) | 0 participants |
| IMC-1121B 10 mg/kg (Cohort 3) | Screen for the Development of Circulating Antibodies Against IMC-1121B (Immunogenicity) | 0 participants |