An Open-Label, Dose-Escalation Study of IMC-20D7S In Participants With Malignant Melanoma
- Conditions
- Malignant Melanoma
- Interventions
- Biological: IMC-20D7S (Cohort 1A)Biological: IMC-20D7S (Cohort 1B)Biological: IMC-20D7S (Cohort 2B)Biological: IMC-20D7S (Cohort 2A)Biological: IMC-20D7S (Cohort 3A)Biological: IMC-20D7S (Cohort 3B)Biological: IMC-20D7S (Cohort 4A)
- Registration Number
- NCT01137006
- Lead Sponsor
- Eli Lilly and Company
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 27
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description IMC-20D7S (1A-4A Cohorts) IMC-20D7S (Cohort 1A) Escalating doses up to 30 milligrams per kilogram (mg/kg) administered intravenously (i.v.) every 2 weeks; includes Cohorts 1A, 2A, 3A, and 4A. IMC-20D7S (1A-4A Cohorts) IMC-20D7S (Cohort 3A) Escalating doses up to 30 milligrams per kilogram (mg/kg) administered intravenously (i.v.) every 2 weeks; includes Cohorts 1A, 2A, 3A, and 4A. IMC-20D7S (1B-3B Cohorts) IMC-20D7S (Cohort 3B) Escalating doses up to 30 mg/kg administered i.v. every 3 weeks; includes Cohorts 1B, 2B, and 3B. IMC-20D7S (1B-3B Cohorts) IMC-20D7S (Cohort 2B) Escalating doses up to 30 mg/kg administered i.v. every 3 weeks; includes Cohorts 1B, 2B, and 3B. IMC-20D7S (1A-4A Cohorts) IMC-20D7S (Cohort 2A) Escalating doses up to 30 milligrams per kilogram (mg/kg) administered intravenously (i.v.) every 2 weeks; includes Cohorts 1A, 2A, 3A, and 4A. IMC-20D7S (1A-4A Cohorts) IMC-20D7S (Cohort 4A) Escalating doses up to 30 milligrams per kilogram (mg/kg) administered intravenously (i.v.) every 2 weeks; includes Cohorts 1A, 2A, 3A, and 4A. IMC-20D7S (1B-3B Cohorts) IMC-20D7S (Cohort 1B) Escalating doses up to 30 mg/kg administered i.v. every 3 weeks; includes Cohorts 1B, 2B, and 3B.
- Primary Outcome Measures
Name Time Method Maximum Tolerated Dose (MTD) of IMC-20D7S Baseline to toxicity [up to end of Cycle 1 (4 or 6-week cycles)] 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 Baseline through 30 days post last dose (up to 31 weeks) A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module.
- Secondary Outcome Measures
Name Time Method IMC-20D7S PK: Half-life (t½) 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. A non-validated assay was used to determine individual serum concentrations of IMC-20D7S. Thus, analyses of PK data were not conducted.
Recommend Doses for Phase 2/3 Studies Based on MTD Baseline to toxicity [up to end of Cycle 1 (4-or 6-week cycles)] It was decided for administrative reasons to discontinue dosing at the provisional MTD rather than progress to Phase 1b.
IMC-20D7S Pharmacokinetics (PK): Maximum Concentration (Cmax) 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. 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) 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. 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) 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. A non-validated assay was used to determine individual serum concentrations of IMC-20D7S. Thus, analyses of PK data were not conducted.
Progression-Free Survival (PFS) First dose to disease progression or death (up to 27 weeks) 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.
Number of Participants Who Develop Antibodies Against IMC-20D7S (Immunogenicity) Prior to the first and second infusion in each cycle up to Cycle 7 (4- and 6-week cycles) 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.
IMC-20D7S PK: Area Under the Concentration Versus Time Curve (AUC) 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. 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 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. A non-validated assay was used to determine individual serum concentrations of IMC-20D7S. Thus, analyses of PK data were not conducted.
Trial Locations
- Locations (1)
ImClone Investigational Site
🇺🇸New York, New York, United States