An Open-Label, Dose-Escalation Study of IMC-20D7S In Participants With Malignant Melanoma

• ClinicalTrials.gov Identifier: NCT01137006
• Recruitment Status: Completed
• First Posted: June 4, 2010
• Results First Posted: June 17, 2019
• Last Update Posted: June 17, 2019
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

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.

Condition or disease	Intervention/treatment	Phase
Malignant Melanoma	Biological: IMC-20D7S (Cohort 1A); Biological: IMC-20D7S (Cohort 2A); Biological: IMC-20D7S (Cohort 3A); Biological: IMC-20D7S (Cohort 4A); Biological: IMC-20D7S (Cohort 1B); Biological: IMC-20D7S (Cohort 2B); Biological: IMC-20D7S (Cohort 3B)	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 27 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: June 2010
• Actual Primary Completion Date: August 2012
• Actual Study Completion Date: August 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: IMC-20D7S (1A-4A Cohorts); Escalating doses up to 30 milligrams per kilogram (mg/kg) administered intravenously (i.v.) every 2 weeks; includes Cohorts 1A, 2A, 3A, and 4A.	Biological: IMC-20D7S (Cohort 1A); 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.; Other Name: LY3012215; Biological: IMC-20D7S (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.; Other Name: LY3012215; Biological: IMC-20D7S (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.; Other Name: LY3012215; Biological: IMC-20D7S (Cohort 4A); 30 mg/kg i.v. every 2 weeks. Administered every other week on Days 1 and 15 of each treatment cycle.; Other Name: LY3012215
Experimental: IMC-20D7S (1B-3B Cohorts); Escalating doses up to 30 mg/kg administered i.v. every 3 weeks; includes Cohorts 1B, 2B, and 3B.	Biological: IMC-20D7S (Cohort 1B); 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.; Other Name: LY3012215; Biological: IMC-20D7S (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.; Other Name: LY3012215; Biological: IMC-20D7S (Cohort 3B); 30 mg/kg i.v. every 3 weeks. Administered every 3 weeks on Days 1 and 22 of each treatment cycle.; Other Name: LY3012215

Outcome Measures

Primary Outcome Measures :

1. Maximum Tolerated Dose (MTD) of IMC-20D7S [ Time Frame: 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.
2. Number of Participants With Serious Adverse Events (SAEs), Other Non-Serious Adverse Events (AEs), or Death [ Time Frame: 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 :

1. IMC-20D7S Pharmacokinetics (PK): Maximum Concentration (Cmax) [ 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. ]
   A non-validated assay was used to determine individual serum concentrations of IMC-20D7S. Thus, analyses of PK data were not conducted.
2. IMC-20D7S PK: Minimal Concentration (Cmin) [ 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. ]
   A non-validated assay was used to determine individual serum concentrations of IMC-20D7S. Thus, analyses of PK data were not conducted.
3. IMC-20D7S PK: Half-life (t½) [ 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. ]
   A non-validated assay was used to determine individual serum concentrations of IMC-20D7S. Thus, analyses of PK data were not conducted.
4. IMC-20D7S PK: Clearance (Cl) [ 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. ]
   A non-validated assay was used to determine individual serum concentrations of IMC-20D7S. Thus, analyses of PK data were not conducted.
5. IMC-20D7S PK: Area Under the Concentration Versus Time Curve (AUC) [ 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. ]
   A non-validated assay was used to determine individual serum concentrations of IMC-20D7S. Thus, analyses of PK data were not conducted.
6. IMC-20D7S PK: Volume of Distribution (Vd) at Steady State [ 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. ]
   A non-validated assay was used to determine individual serum concentrations of IMC-20D7S. Thus, analyses of PK data were not conducted.
7. Number of Participants Who Develop Antibodies Against IMC-20D7S (Immunogenicity) [ Time Frame: 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.
8. Progression-Free Survival (PFS) [ Time Frame: 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.
9. Recommend Doses for Phase 2/3 Studies Based on MTD [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Massachusetts

ImClone Investigational Site

Boston, Massachusetts, United States, 02114

United States, New York

ImClone Investigational Site

New York, New York, United States, 10021

Sponsors and Collaborators

Eli Lilly and Company

Investigators

• Study Director: E-mail: ClinicalTrials@ ImClone.com; Eli Lilly and Company

More Information

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01137006
• Other Study ID Numbers: 13945; CP22-0901 ( Other Identifier: ImClone, LLC ); I4Z-IE-JDEA ( Other Identifier: Eli Lilly and Company )
• First Posted: June 4, 2010
• Results First Posted: June 17, 2019
• Last Update Posted: June 17, 2019
• Last Verified: March 2019

Keywords provided by Eli Lilly and Company:

Melanoma; Phase I; antibody; melanin; tyrosinase related protein 1; glycoprotein; 20D7S

Additional relevant MeSH terms:

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas