Back to resultsAn Open-Label, Dose-Escalation Study of IMC-20D7S In Participants With Malignant Melanoma
Primary Purpose
Malignant Melanoma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
IMC-20D7S (Cohort 1A)
IMC-20D7S (Cohort 2A)
IMC-20D7S (Cohort 3A)
IMC-20D7S (Cohort 4A)
IMC-20D7S (Cohort 1B)
IMC-20D7S (Cohort 2B)
IMC-20D7S (Cohort 3B)
Sponsored by
About this trial
This is an interventional treatment trial for Malignant Melanoma focused on measuring Melanoma, Phase I, antibody, melanin, tyrosinase related protein 1, glycoprotein, 20D7S
Eligibility Criteria
Inclusion Criteria:
- Participant has histologically or cytologically confirmed cutaneous, mucosal, or uveal malignant melanoma which has progressed after or during at least 1 treatment with standard cytotoxic treatment or/and immunotherapy [for example (e.g.), treatment with cytokines, monoclonal antibodies, and vaccines] and is not regarded to be a candidate for a potentially curative, higher priority treatment for melanoma
- Participant is ≥18 years of age
- Participant has either measurable disease as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) or evaluable disease
- At least 21 days must have elapsed from major surgery, prior chemotherapy, prior treatment with an investigational agent or device, or prior radiation therapy. Relative to participant's treatment with non-approved biological products (eg, monoclonal antibodies), a minimum of 2 half-lives must have passed for eligibility to be considered
- Participant has resolution of all clinically significant toxic effects of prior cancer therapy to Grade ≤1 according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.02 (NCI-CTCAE v4.02)
- Participant has adequate hematological function, hepatic function, and renal function
Exclusion Criteria:
- Participant has undergone major surgery [e.g., laparotomy, thoracotomy, removal of organ(s)] within 21 days prior to study entry
- Participant has elective or planned surgery to be conducted during the trial
- Participant has documented and/or symptomatic brain or leptomeningeal metastases
- Participant is receiving systemic steroids or other immunosuppressive medications. (Intermittent use of steroid-containing medications e.g., for asthma exacerbation or for skin lesions is permitted)
- Participant has an uncontrolled undercurrent illness
- Participant has a concurrent active malignancy other than adequately treated nonmelanomatous skin cancer or other noninvasive carcinoma or in situ neoplasm
- Participant has a known allergy to any of the treatment components (monoclonal antibodies or other therapeutic proteins such as fresh frozen plasma, human serum albumin, cytokines, or interleukins). In the event that there is suspicion the participant may have allergies, the participant should be excluded
- Participant is pregnant or lactating
- Participant has known human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS) infection
Sites / Locations
- ImClone Investigational Site
- ImClone Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
IMC-20D7S (1A-4A Cohorts)
IMC-20D7S (1B-3B Cohorts)
Arm Description
Escalating doses up to 30 milligrams per kilogram (mg/kg) administered intravenously (i.v.) every 2 weeks; includes Cohorts 1A, 2A, 3A, and 4A.
Escalating doses up to 30 mg/kg administered i.v. every 3 weeks; includes Cohorts 1B, 2B, and 3B.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01137006
Brief Title
An Open-Label, Dose-Escalation Study of IMC-20D7S In Participants With Malignant Melanoma
Official Title
An Open-Label, Dose-Escalation Phase 1/1b Study of the Anti-gp75 Monoclonal Antibody IMC-20D7S In Patients With Malignant Melanoma Who Have Progressed After or During at Least One Treatment With Standard Cytotoxic Treatment or/and Immunotherapy Therapy or For Whom Standard Therapy is Not Indicated
Study Type
Interventional
2. Study Status
Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
June 2010 (undefined)
Primary Completion Date
August 2012 (Actual)
Study Completion Date
August 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Melanoma
Keywords
Melanoma, Phase I, antibody, melanin, tyrosinase related protein 1, glycoprotein, 20D7S
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
27 (Actual)
8. Arms, Groups, and Interventions
Arm Title
IMC-20D7S (1A-4A Cohorts)
Arm Type
Experimental
Arm Description
Escalating doses up to 30 milligrams per kilogram (mg/kg) administered intravenously (i.v.) every 2 weeks; includes Cohorts 1A, 2A, 3A, and 4A.
Arm Title
IMC-20D7S (1B-3B Cohorts)
Arm Type
Experimental
Arm Description
Escalating doses up to 30 mg/kg administered i.v. every 3 weeks; includes Cohorts 1B, 2B, and 3B.
Intervention Type
Biological
Intervention Name(s)
IMC-20D7S (Cohort 1A)
Other Intervention Name(s)
LY3012215
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
IMC-20D7S (Cohort 2A)
Other Intervention Name(s)
LY3012215
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
IMC-20D7S (Cohort 3A)
Other Intervention Name(s)
LY3012215
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
IMC-20D7S (Cohort 4A)
Other Intervention Name(s)
LY3012215
Intervention Description
30 mg/kg i.v. every 2 weeks.
Administered every other week on Days 1 and 15 of each treatment cycle.
Intervention Type
Biological
Intervention Name(s)
IMC-20D7S (Cohort 1B)
Other Intervention Name(s)
LY3012215
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
IMC-20D7S (Cohort 2B)
Other Intervention Name(s)
LY3012215
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
IMC-20D7S (Cohort 3B)
Other Intervention Name(s)
LY3012215
Intervention Description
30 mg/kg i.v. every 3 weeks.
Administered every 3 weeks on Days 1 and 22 of each treatment cycle.
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose (MTD) of IMC-20D7S
Description
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)]
Title
Number of Participants With Serious Adverse Events (SAEs), Other Non-Serious Adverse Events (AEs), or Death
Description
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)
Secondary Outcome Measure Information:
Title
IMC-20D7S Pharmacokinetics (PK): Maximum Concentration (Cmax)
Description
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.
Title
IMC-20D7S PK: Minimal Concentration (Cmin)
Description
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.
Title
IMC-20D7S PK: Half-life (t½)
Description
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.
Title
IMC-20D7S PK: Clearance (Cl)
Description
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.
Title
IMC-20D7S PK: Area Under the Concentration Versus Time Curve (AUC)
Description
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.
Title
IMC-20D7S PK: Volume of Distribution (Vd) at Steady State
Description
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.
Title
Number of Participants Who Develop Antibodies Against IMC-20D7S (Immunogenicity)
Description
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)
Title
Progression-Free Survival (PFS)
Description
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)
Title
Recommend Doses for Phase 2/3 Studies Based on MTD
Description
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)]
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participant has histologically or cytologically confirmed cutaneous, mucosal, or uveal malignant melanoma which has progressed after or during at least 1 treatment with standard cytotoxic treatment or/and immunotherapy [for example (e.g.), treatment with cytokines, monoclonal antibodies, and vaccines] and is not regarded to be a candidate for a potentially curative, higher priority treatment for melanoma
Participant is ≥18 years of age
Participant has either measurable disease as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) or evaluable disease
At least 21 days must have elapsed from major surgery, prior chemotherapy, prior treatment with an investigational agent or device, or prior radiation therapy. Relative to participant's treatment with non-approved biological products (eg, monoclonal antibodies), a minimum of 2 half-lives must have passed for eligibility to be considered
Participant has resolution of all clinically significant toxic effects of prior cancer therapy to Grade ≤1 according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.02 (NCI-CTCAE v4.02)
Participant has adequate hematological function, hepatic function, and renal function
Exclusion Criteria:
Participant has undergone major surgery [e.g., laparotomy, thoracotomy, removal of organ(s)] within 21 days prior to study entry
Participant has elective or planned surgery to be conducted during the trial
Participant has documented and/or symptomatic brain or leptomeningeal metastases
Participant is receiving systemic steroids or other immunosuppressive medications. (Intermittent use of steroid-containing medications e.g., for asthma exacerbation or for skin lesions is permitted)
Participant has an uncontrolled undercurrent illness
Participant has a concurrent active malignancy other than adequately treated nonmelanomatous skin cancer or other noninvasive carcinoma or in situ neoplasm
Participant has a known allergy to any of the treatment components (monoclonal antibodies or other therapeutic proteins such as fresh frozen plasma, human serum albumin, cytokines, or interleukins). In the event that there is suspicion the participant may have allergies, the participant should be excluded
Participant is pregnant or lactating
Participant has known human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS) infection
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
E-mail: ClinicalTrials@ ImClone.com
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
ImClone Investigational Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
ImClone Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
12. IPD Sharing Statement
Learn more about this trial
An Open-Label, Dose-Escalation Study of IMC-20D7S In Participants With Malignant Melanoma
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