A dose-escalation study designed to determine the safety, maximum tolerated dose (MTD), anti-melanoma activity, antibody blood levels and progression-free survival (PFS) in participants with malignant melanoma receiving IMC-20D7S either every 2 weeks or every 3 weeks.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
27
5 mg/kg i.v. every 2 weeks. Administered every other week on Days 1 and 15 of each treatment cycle. If no dose-limiting toxicity (DLT) in first 3 participants or 1 DLT in 6 participants, then enrollment into Cohort 2A.
10 mg/kg i.v. every 2 weeks. Administered every other week on Days 1 and 15 of each treatment cycle. If no DLT in first 3 participants or 1 DLT in 6 participants in Cohort 2A, then enrollment into Cohort 3A.
20 mg/kg i.v. every 2 weeks. Administered every other week on Days 1 and 15 of each treatment cycle. If no DLT in first 3 participants or 1 DLT in 6 participants in Cohort 3A, then enrollment into Cohort 4A.
ImClone Investigational Site
Boston, Massachusetts, United States
ImClone Investigational Site
New York, New York, United States
Maximum Tolerated Dose (MTD) of IMC-20D7S
The MTD was defined as the dose preceding the dose level at which 2 participants experienced a dose-limiting toxicity (DLT) during treatment Cycle 1. A DLT was defined as any Grade 3 or above toxicity that emerged during study treatment and was clearly not attributable to malignant melanoma or co-medication and was possibly, probably, or definitely related to IMC-20D7S in the judgment of the investigator. No DLT was observed in the study; a provisional MTD was established.
Time frame: Baseline to toxicity [up to end of Cycle 1 (4 or 6-week cycles)]
Number of Participants With Serious Adverse Events (SAEs), Other Non-Serious Adverse Events (AEs), or Death
A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module.
Time frame: Baseline through 30 days post last dose (up to 31 weeks)
IMC-20D7S Pharmacokinetics (PK): Maximum Concentration (Cmax)
A non-validated assay was used to determine individual serum concentrations of IMC-20D7S. Thus, analyses of PK data were not conducted.
Time frame: Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 hours (h) post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
IMC-20D7S PK: Minimal Concentration (Cmin)
A non-validated assay was used to determine individual serum concentrations of IMC-20D7S. Thus, analyses of PK data were not conducted.
Time frame: Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
IMC-20D7S PK: Half-life (t½)
A non-validated assay was used to determine individual serum concentrations of IMC-20D7S. Thus, analyses of PK data were not conducted.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
30 mg/kg i.v. every 2 weeks. Administered every other week on Days 1 and 15 of each treatment cycle.
10 mg/kg i.v. every 3 weeks. Administered every 3 weeks on Days 1 and 22 of each treatment cycle. If no dose-limiting toxicity (DLT) in first 3 participants or 1 DLT in 6 participants in Cohort 1B, then enrollment into Cohort 2B.
20 mg/kg i.v. every 3 weeks. Administered every 3 weeks on Days 1 and 22 of each treatment cycle. If no DLT in first 3 participants or 1 DLT in 6 participants in Cohort 2B, then enrollment into Cohort 3B.
30 mg/kg i.v. every 3 weeks. Administered every 3 weeks on Days 1 and 22 of each treatment cycle.
Time frame: Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
IMC-20D7S PK: Clearance (Cl)
A non-validated assay was used to determine individual serum concentrations of IMC-20D7S. Thus, analyses of PK data were not conducted.
Time frame: Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
IMC-20D7S PK: Area Under the Concentration Versus Time Curve (AUC)
A non-validated assay was used to determine individual serum concentrations of IMC-20D7S. Thus, analyses of PK data were not conducted.
Time frame: Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
IMC-20D7S PK: Volume of Distribution (Vd) at Steady State
A non-validated assay was used to determine individual serum concentrations of IMC-20D7S. Thus, analyses of PK data were not conducted.
Time frame: Cycles 1 and 3: Prior to, immediately after, and 0.5, 1, 2, 4, 8, 24, 48 (Cycle 3 only), 96, 168, 240, and 336 h post first infusion. Cycles 2 and 4: Prior to and 1 h post first infusion.
Number of Participants Who Develop Antibodies Against IMC-20D7S (Immunogenicity)
Planned analyses for immunogenicity were not completed. A decision was made not to develop a validated immunogenicity assay because of the exploratory nature of the study and the analyses.
Time frame: Prior to the first and second infusion in each cycle up to Cycle 7 (4- and 6-week cycles)
Progression-Free Survival (PFS)
PFS was determined for participants who went beyond their first disease assessment and completed at least 1 treatment beyond Week 1 of treatment Cycle 3.
Time frame: First dose to disease progression or death (up to 27 weeks)
Recommend Doses for Phase 2/3 Studies Based on MTD
It was decided for administrative reasons to discontinue dosing at the provisional MTD rather than progress to Phase 1b.
Time frame: Baseline to toxicity [up to end of Cycle 1 (4-or 6-week cycles)]