Trial Outcomes & Findings for Study of IMC-1121B in Patients With Advanced Solid Tumors (NCT NCT01005355)
NCT ID: NCT01005355
Last Updated: 2014-06-18
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
15 participants
Primary outcome timeframe
Baseline to study completion up to 48 weeks
Results posted on
2014-06-18
Participant Flow
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.
Participant milestones
| Measure |
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.
|
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.
|
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.
|
|---|---|---|---|
|
Overall Study
STARTED
|
3
|
6
|
6
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
3
|
6
|
6
|
|
Overall Study
COMPLETED
|
3
|
6
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study of IMC-1121B in Patients With Advanced Solid Tumors
Baseline characteristics by cohort
| Measure |
IMC-1121B 6 mg/kg (Cohort 1)
n=3 Participants
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.
|
IMC-1121B 8 mg/kg (Cohort 2)
n=6 Participants
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.
|
IMC-1121B 10 mg/kg (Cohort 3)
n=6 Participants
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.
|
Total
n=15 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
3 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
13 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Asian
|
3 participants
n=5 Participants
|
6 participants
n=7 Participants
|
6 participants
n=5 Participants
|
15 participants
n=4 Participants
|
|
Region of Enrollment
Japan
|
3 participants
n=5 Participants
|
6 participants
n=7 Participants
|
6 participants
n=5 Participants
|
15 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline to study completion up to 48 weeksPopulation: All participants who received at least 1 dose of study drug.
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.
Outcome measures
| Measure |
IMC-1121B 6 mg/kg (Cohort 1)
n=3 Participants
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.
|
IMC-1121B 8 mg/kg (Cohort 2)
n=6 Participants
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.
|
IMC-1121B 10 mg/kg (Cohort 3)
n=6 Participants
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.
|
|---|---|---|---|
|
Number of Participants With Drug-Related Adverse Events
AE of any grade
|
3 participants
|
6 participants
|
6 participants
|
|
Number of Participants With Drug-Related Adverse Events
AE of Grade ≥3
|
0 participants
|
0 participants
|
1 participants
|
|
Number of Participants With Drug-Related Adverse Events
SAE
|
0 participants
|
0 participants
|
1 participants
|
|
Number of Participants With Drug-Related Adverse Events
AE resulting in death
|
0 participants
|
0 participants
|
0 participants
|
PRIMARY outcome
Timeframe: Day 1 to Day 15 of Cycles 1 and 2 of a 6-week cyclePopulation: All participants in Cohorts 1 and 2 who received study drug and had sufficient pharmacokinetics data to calculate Cmax for Cycles 1 and 2.
Outcome measures
| Measure |
IMC-1121B 6 mg/kg (Cohort 1)
n=3 Participants
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.
|
IMC-1121B 8 mg/kg (Cohort 2)
n=6 Participants
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.
|
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.
|
|---|---|---|---|
|
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
|
371 micrograms/milliliter (mcg/mL)
Standard Deviation 113
|
—
|
|
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)
Standard Deviation NA
Only 1 participant included in the analysis, therefore standard deviation is not calculable.
|
694 micrograms/milliliter (mcg/mL)
Standard Deviation 123
|
—
|
PRIMARY outcome
Timeframe: Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdosePopulation: Zero participants were analyzed due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5.
Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, Cmax could not be calculated.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Day 1 to Day 15 of Cycles 1 and 2 of a 6-week cyclePopulation: 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.
AUC for Cycle 1 is AUC from time zero to infinity \[AUC(0-∞)\] and for Cycle 2 is AUC over a dosing interval (AUCτ).
Outcome measures
| Measure |
IMC-1121B 6 mg/kg (Cohort 1)
n=1 Participants
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.
|
IMC-1121B 8 mg/kg (Cohort 2)
n=2 Participants
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.
|
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.
|
|---|---|---|---|
|
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)
Standard Deviation NA
Only 1 participant included in the analysis, therefore standard deviation is not calculable.
|
73800 micrograms*hour/milliliter (mcg*h/mL)
Standard Deviation NA
Only 1 participant included in the analysis, therefore standard deviation is not calculable.
|
—
|
|
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)
Standard Deviation NA
Only 1 participant included in the analysis, therefore standard deviation is not calculable.
|
102000 micrograms*hour/milliliter (mcg*h/mL)
Standard Deviation 10400
|
—
|
PRIMARY outcome
Timeframe: Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdosePopulation: Zero participants were analyzed due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5.
Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, AUC could not be calculated.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Day 1 to Day 15 of Cycles 1 and 2 of a 6-week cyclePopulation: 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.
Outcome measures
| Measure |
IMC-1121B 6 mg/kg (Cohort 1)
n=3 Participants
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.
|
IMC-1121B 8 mg/kg (Cohort 2)
n=2 Participants
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.
|
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.
|
|---|---|---|---|
|
IMC-1121B Pharmacokinetics: Half-Life (t1/2) - Cohorts 1 and 2 During Cycles 1 and 2
Cycle 1
|
158 hours
Full Range NA • Interval 129.0 to 166.0
|
165 hours
Full Range NA • Interval 140.0 to 191.0
|
—
|
|
IMC-1121B Pharmacokinetics: Half-Life (t1/2) - Cohorts 1 and 2 During Cycles 1 and 2
Cycle 2 (n=0, 0)
|
NA hours
Full Range NA
Zero participants were analyzed due to the sparse pharmacokinetic sampling schedule.
|
NA hours
Full Range NA
Zero participants were analyzed due to the sparse pharmacokinetic sampling schedule.
|
—
|
PRIMARY outcome
Timeframe: Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdosePopulation: Zero participants were analyzed due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5.
Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, t1/2 could not be calculated.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Day 1 to Day 15 of Cycles 1 and 2 of a 6-week cyclePopulation: 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.
Outcome measures
| Measure |
IMC-1121B 6 mg/kg (Cohort 1)
n=1 Participants
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.
|
IMC-1121B 8 mg/kg (Cohort 2)
n=1 Participants
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.
|
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.
|
|---|---|---|---|
|
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)
Standard Deviation NA
Only 1 participant included in the analysis, therefore standard deviation is not calculable.
|
21.4 milliliters/kilogram (mL/kg)
Standard Deviation NA
Only 1 participant included in the analysis, therefore standard deviation is not calculable.
|
—
|
|
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)
Standard Deviation NA
Vss is not calculated for multiple doses.
|
NA milliliters/kilogram (mL/kg)
Standard Deviation NA
Vss is not calculated for multiple doses.
|
—
|
PRIMARY outcome
Timeframe: Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdosePopulation: Zero participants were analyzed due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5.
Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, Vss could not be calculated.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Day 1 to Day 22 of Cycles 1 and 2 of a 6-week cyclePopulation: All participants in Cohort 3 who received study drug and had sufficient pharmacokinetics data to calculate Cmax for Cycles 1 and 2.
Outcome measures
| Measure |
IMC-1121B 6 mg/kg (Cohort 1)
n=6 Participants
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.
|
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.
|
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.
|
|---|---|---|---|
|
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 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 outcome
Timeframe: Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdosePopulation: Zero participants were analyzed due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5.
Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, Cmax could not be calculated.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Day 1 to Day 22 of Cycles 1 and 2 of a 6-week cyclePopulation: 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.
AUC for Cycle 1 is AUC from time zero to infinity \[AUC(0-∞)\] and for Cycle 2 is AUC over a dosing interval (AUCτ).
Outcome measures
| Measure |
IMC-1121B 6 mg/kg (Cohort 1)
n=2 Participants
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.
|
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.
|
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.
|
|---|---|---|---|
|
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 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 outcome
Timeframe: Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdosePopulation: Zero participants were analyzed due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5.
Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, AUC could not be calculated.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Day 1 to Day 22 of Cycles 1 and 2 of a 6-week cyclePopulation: All participants in Cohort 3 who received study drug and had sufficient pharmacokinetics data to calculate t1/2 for Cycles 1 and 2.
Outcome measures
| Measure |
IMC-1121B 6 mg/kg (Cohort 1)
n=3 Participants
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.
|
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.
|
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.
|
|---|---|---|---|
|
IMC-1121B Pharmacokinetics: Half-Life (t1/2) - Cohort 3 During Cycles 1 and 2
Cycle 1
|
234 hours
Full Range NA • Interval 166.0 to 241.0
|
—
|
—
|
|
IMC-1121B Pharmacokinetics: Half-Life (t1/2) - Cohort 3 During Cycles 1 and 2
Cycle 2 (n=1)
|
329 hours
Full Range NA • Interval 329.0 to 329.0
|
—
|
—
|
PRIMARY outcome
Timeframe: Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour postdosePopulation: Zero participants were analyzed due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5.
Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, t1/2 could not be calculated.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Day 1 and Day 22 of Cycles 1 and 2 of a 6-week cyclePopulation: 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.
Outcome measures
| Measure |
IMC-1121B 6 mg/kg (Cohort 1)
n=2 Participants
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.
|
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.
|
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.
|
|---|---|---|---|
|
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 Pharmacokinetics: Steady State Volume of Distribution (Vss) - Cohort 3 During Cycles 1 and 2
Cycle 2 (n=0)
|
NA milliliters/kilogram (mL/kg)
Standard Deviation NA
Vss is not calculated for multiple doses.
|
—
|
—
|
PRIMARY outcome
Timeframe: Cycles 3, 4 and 5 of a 6-week cycle: predose and 1 hour post-dosePopulation: Zero participants were analyzed due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5.
Due to the sparse pharmacokinetic sampling employed in Cycles 3 to 5, Vss could not be calculated.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline to study completion up to 48 weeksPopulation: All participants who received at least 1 dose of study drug.
Data presented are the number of participants with treatment emergent antibody positive.
Outcome measures
| Measure |
IMC-1121B 6 mg/kg (Cohort 1)
n=3 Participants
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.
|
IMC-1121B 8 mg/kg (Cohort 2)
n=6 Participants
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.
|
IMC-1121B 10 mg/kg (Cohort 3)
n=6 Participants
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.
|
|---|---|---|---|
|
Screen for the Development of Circulating Antibodies Against IMC-1121B (Immunogenicity)
|
0 participants
|
0 participants
|
0 participants
|
Adverse Events
IMC-1121B 6 mg/kg (Cohort 1)
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
IMC-1121B 8 mg/kg (Cohort 2)
Serious events: 2 serious events
Other events: 6 other events
Deaths: 0 deaths
IMC-1121B 10 mg/kg (Cohort 3)
Serious events: 2 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
IMC-1121B 6 mg/kg (Cohort 1)
n=3 participants at risk
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.
|
IMC-1121B 8 mg/kg (Cohort 2)
n=6 participants at risk
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.
|
IMC-1121B 10 mg/kg (Cohort 3)
n=6 participants at risk
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.
|
|---|---|---|---|
|
Nervous system disorders
Syncope
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
|
Surgical and medical procedures
Hospitalisation
|
33.3%
1/3 • Number of events 1
|
33.3%
2/6 • Number of events 2
|
16.7%
1/6 • Number of events 1
|
Other adverse events
| Measure |
IMC-1121B 6 mg/kg (Cohort 1)
n=3 participants at risk
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.
|
IMC-1121B 8 mg/kg (Cohort 2)
n=6 participants at risk
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.
|
IMC-1121B 10 mg/kg (Cohort 3)
n=6 participants at risk
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.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Leukopenia
|
33.3%
1/3 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/3
|
16.7%
1/6 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
|
Cardiac disorders
Pericardial effusion
|
0.00%
0/3
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
|
Eye disorders
Conjunctival haemorrhage
|
0.00%
0/3
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
|
Eye disorders
Eyelid oedema
|
0.00%
0/3
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
|
Eye disorders
Myodesopsia
|
0.00%
0/3
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
|
General disorders
Chills
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
|
General disorders
Face oedema
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
|
General disorders
Fatigue
|
33.3%
1/3 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
50.0%
3/6 • Number of events 5
|
|
General disorders
Injection site pain
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
|
General disorders
Injection site rash
|
33.3%
1/3 • Number of events 5
|
16.7%
1/6 • Number of events 1
|
50.0%
3/6 • Number of events 3
|
|
General disorders
Oedema peripheral
|
0.00%
0/3
|
16.7%
1/6 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
|
General disorders
Pyrexia
|
33.3%
1/3 • Number of events 1
|
33.3%
2/6 • Number of events 2
|
66.7%
4/6 • Number of events 4
|
|
Gastrointestinal disorders
Abdominal pain upper
|
66.7%
2/3 • Number of events 2
|
0.00%
0/6
|
0.00%
0/6
|
|
Gastrointestinal disorders
Anal haemorrhage
|
33.3%
1/3 • Number of events 1
|
0.00%
0/6
|
0.00%
0/6
|
|
Gastrointestinal disorders
Constipation
|
33.3%
1/3 • Number of events 1
|
0.00%
0/6
|
0.00%
0/6
|
|
Gastrointestinal disorders
Diarrhoea
|
66.7%
2/3 • Number of events 4
|
33.3%
2/6 • Number of events 2
|
16.7%
1/6 • Number of events 1
|
|
Gastrointestinal disorders
Gastritis
|
33.3%
1/3 • Number of events 1
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
|
Gastrointestinal disorders
Gingival bleeding
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
|
Gastrointestinal disorders
Gingivitis
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/3
|
16.7%
1/6 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
|
Gastrointestinal disorders
Stomatitis
|
33.3%
1/3 • Number of events 1
|
0.00%
0/6
|
16.7%
1/6 • Number of events 2
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
|
Infections and infestations
Abscess oral
|
0.00%
0/3
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/3
|
50.0%
3/6 • Number of events 3
|
0.00%
0/6
|
|
Infections and infestations
Oral herpes
|
0.00%
0/3
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/3
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
|
Investigations
Alanine aminotransferase increased
|
33.3%
1/3 • Number of events 1
|
33.3%
2/6 • Number of events 2
|
33.3%
2/6 • Number of events 2
|
|
Investigations
Aspartate aminotransferase increased
|
66.7%
2/3 • Number of events 2
|
33.3%
2/6 • Number of events 2
|
33.3%
2/6 • Number of events 2
|
|
Investigations
Blood albumin decreased
|
0.00%
0/3
|
33.3%
2/6 • Number of events 2
|
0.00%
0/6
|
|
Investigations
Blood alkaline phosphatase increased
|
0.00%
0/3
|
16.7%
1/6 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
|
Investigations
Blood amylase increased
|
0.00%
0/3
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
|
Investigations
Blood urine present
|
0.00%
0/3
|
16.7%
1/6 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
|
Investigations
Electrocardiogram T wave amplitude decreased
|
0.00%
0/3
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
|
Investigations
Weight decreased
|
0.00%
0/3
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
|
Investigations
Weight increased
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
|
Metabolism and nutrition disorders
Anorexia
|
33.3%
1/3 • Number of events 1
|
0.00%
0/6
|
33.3%
2/6 • Number of events 3
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
0.00%
0/3
|
16.7%
1/6 • Number of events 1
|
33.3%
2/6 • Number of events 3
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypovolaemia
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
33.3%
1/3 • Number of events 1
|
0.00%
0/6
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
33.3%
1/3 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
33.3%
1/3 • Number of events 1
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lymphangiosis carcinomatosa
|
0.00%
0/3
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
|
Nervous system disorders
Dizziness
|
66.7%
2/3 • Number of events 2
|
16.7%
1/6 • Number of events 2
|
0.00%
0/6
|
|
Nervous system disorders
Headache
|
33.3%
1/3 • Number of events 1
|
66.7%
4/6 • Number of events 5
|
83.3%
5/6 • Number of events 10
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/3
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
|
Renal and urinary disorders
Proteinuria
|
0.00%
0/3
|
50.0%
3/6 • Number of events 4
|
0.00%
0/6
|
|
Reproductive system and breast disorders
Breast haemorrhage
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
100.0%
1/1 • Number of events 3
|
0.00%
0/5
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
0.00%
0/3
|
0.00%
0/6
|
33.3%
2/6 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/3
|
33.3%
2/6 • Number of events 2
|
16.7%
1/6 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal discomfort
|
0.00%
0/3
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Acne
|
66.7%
2/3 • Number of events 3
|
16.7%
1/6 • Number of events 1
|
16.7%
1/6 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Haemorrhage subcutaneous
|
33.3%
1/3 • Number of events 1
|
0.00%
0/6
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
66.7%
2/3 • Number of events 2
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Purpura
|
0.00%
0/3
|
16.7%
1/6 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash
|
33.3%
1/3 • Number of events 1
|
0.00%
0/6
|
33.3%
2/6 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
|
Vascular disorders
Hypertension
|
33.3%
1/3 • Number of events 1
|
50.0%
3/6 • Number of events 9
|
33.3%
2/6 • Number of events 2
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee 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 publication 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.
- Publication restrictions are in place
Restriction type: OTHER