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

11 maart 2019 bijgewerkt door: Eli Lilly and Company

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

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.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Studietype

Ingrijpend

Inschrijving (Werkelijk)

27

Fase

  • Fase 1

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Verenigde Staten
    • Massachusetts
      • Boston, Massachusetts, Verenigde Staten, 02114
        • ImClone Investigational Site
    • New York
      • New York, New York, Verenigde Staten, 10021
        • ImClone Investigational Site

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

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

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Niet-gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: 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.
Biologisch: 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.

Andere namen:
  • LY3012215
Biologisch: 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.

Andere namen:
  • LY3012215
Biologisch: 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.

Andere namen:
  • LY3012215
Biologisch: 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.

Andere namen:
  • LY3012215
Experimenteel: IMC-20D7S (1B-3B Cohorts)
Escalating doses up to 30 mg/kg administered i.v. every 3 weeks; includes Cohorts 1B, 2B, and 3B.
Biologisch: 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.

Andere namen:
  • LY3012215
Biologisch: 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.

Andere namen:
  • LY3012215
Biologisch: 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.

Andere namen:
  • LY3012215

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Maximum Tolerated Dose (MTD) of IMC-20D7S
Tijdsspanne: 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.
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
Tijdsspanne: 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.
Baseline through 30 days post last dose (up to 31 weeks)

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
IMC-20D7S Pharmacokinetics (PK): Maximum Concentration (Cmax)
Tijdsspanne: 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.
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)
Tijdsspanne: 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.
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)
Tijdsspanne: 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.
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)
Tijdsspanne: 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.
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)
Tijdsspanne: 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.
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
Tijdsspanne: 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.
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)
Tijdsspanne: 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.
Prior to the first and second infusion in each cycle up to Cycle 7 (4- and 6-week cycles)
Progression-Free Survival (PFS)
Tijdsspanne: 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.
First dose to disease progression or death (up to 27 weeks)
Recommend Doses for Phase 2/3 Studies Based on MTD
Tijdsspanne: 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.
Baseline to toxicity [up to end of Cycle 1 (4-or 6-week cycles)]

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Eli Lilly and Company

Onderzoekers

  • Studie directeur: E-mail: ClinicalTrials@ ImClone.com, Eli Lilly and Company

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 juni 2010

Primaire voltooiing (Werkelijk)

1 augustus 2012

Studie voltooiing (Werkelijk)

1 augustus 2012

Studieregistratiedata

Eerst ingediend

2 juni 2010

Eerst ingediend dat voldeed aan de QC-criteria

3 juni 2010

Eerst geplaatst (Schatting)

4 juni 2010

Updates van studierecords

Laatste update geplaatst (Werkelijk)

17 juni 2019

Laatste update ingediend die voldeed aan QC-criteria

11 maart 2019

Laatst geverifieerd

1 maart 2019

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • 13945
  • CP22-0901 (Andere identificatie: ImClone, LLC)
  • I4Z-IE-JDEA (Andere identificatie: Eli Lilly and Company)

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