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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
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.
ImClone Investigational Site
Tokyo, Japan
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
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
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
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
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
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
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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
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
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
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
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
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
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
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
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
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
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
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