Efficacy Study of Pharmacokinetic(PK)/Pharmacodynamic(PD) Relationship of Monotherapy MORAb-004 in Metastatic Melanoma

A Study of the Efficacy and PK/PD Relationship of Monotherapy MORAb-004 in Subjects With Metastatic Melanoma

This is a global, Phase 2, open label, dose selection, proof-of-concept study to assess progression free survival in subjects with metastatic melanoma.

Approximately 80 subjects at 29 sites in the U.S., U.K., Germany and Australia will be randomized into one of two dose groups: 2 mg/kg, 4 mg/kg. Weekly treatment will continue until disease progression.

Subjects must have measurable disease by CT Scan or MRI and must have completed at least one prior round of chemotherapy.

Subjects will be assessed for Efficacy, PK/PD, Overall survival, and Safety (Adverse Events/Adverse Events of Interest, Electrocardiograms (ECG's), clinical labs, physical exams/vital signs, tolerability).

Study Overview

• Status: Completed
• Conditions: Metastatic Melanoma
• Intervention / Treatment: Biological: MORAb-004 (monoclonal antibody)

Detailed Description

MORAb-004 is a monoclonal antibody directed against endosialin, a cell surface glycoprotein, which is expressed on cells involved in tumor vasculature. Studies have found endosialin to play a key role in tumor growth and neovessel formation in numerous cancer types including melanoma. Preclinical pharmacological studies have shown that MORAb-004 is a potentially useful anti-cancer agent. This clinical trial is being performed to determine the efficacy of MORAb-004 at two dose levels in subjects with metastatic melanoma, as well as to establish serum pharmacokinetics and pharmacodynamics of the antibody.

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Sydney Cancer Center - Royal Prince Alfred Hospital
    • Waratah, New South Wales, Australia, 2298
      • Newcastle Melanoma Unit, Calvery Mater Newcastle
    • Westmead, New South Wales, Australia, 2145
      • The Crown Princess Mary Cancer Centre, Westmead Hospital
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
• Germany
  • Essen, Germany, 45147
    • Universitätsklinikum Essen, Klinik für Dermatologie
  • Mainz, Germany, 55131
    • Universitäts-Hautklinik
  • Tuebingen, Germany, 72076
    • Eberhard Karls University Tuebingen
• United Kingdom
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden Hospital
  • Sheffield, United Kingdom, S10 2SJ
    • Weston Park Hospital
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 19454
      • Pinnacle Oncology
  • California
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic and Research Institute
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center, Anschutz Cancer Pavilion
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago
    • Park Ridge, Illinois, United States, 60068
      • Oncology Specialists, SC
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 19454
      • University of Minnesota
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Jersey
    • Morristown, New Jersey, United States, 07962
      • Atlantic Health
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
    • New York, New York, United States, 10016
      • New York University Cancer Institute
  • North Carolina
    • Chapel Hill, North Carolina, United States, 19454
      • University of North Carolina at Chapel Hill
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18051
      • St. Luke's Hospital & Health Network
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Cancer Institute
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah Huntsman Cancer Institute

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Be surgically sterile or consent to use a medically acceptable method of contraception throughout the study period.
• Histologically confirmed diagnosis of metastatic melanoma
• At least 1 prior systemic treatment for metastatic melanoma with disease progression following treatment
• Measurable disease, as defined by RECIST v1.1, assessed within 4 weeks prior to study entry
• At least 3 week interval between first infusion of test article and most recent prior systemic anticancer therapy. All treatment-associated toxicity must be resolved to less than or equal to Grade 1 before the administration of MORAb-004
• Have a life expectancy of at least 3 months as estimated by the investigator
• Have other significant medical conditions well-controlled and stable, in the opinion of the investigator, for at least 30 days prior to Study Day 1
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Have sites of disease amenable to the protocol-specified biopsy (Note: All participants will have protocol-specified biopsy at Screening. The second, on-treatment biopsy will be mandatory in the first 30 randomized participants only. For all other participants, the second biopsy is optional.
• Laboratory tests results prior to Study Day 1 within limits as outlined in protocol

Exclusion Criteria:

• Have received no prior systemic treatment for metastatic melanoma
• Evidence of other active malignancy requiring treatment within the last 5 years (other than basal cell or squamous cell carcinoma of the skin), or active brain metastasis
• Clinically significant heart disease (Congestive heart failure of New York Heart Association [NYHA] Class 3 or 4, angina not well controlled by medication, or myocardial infarction within 6 mos.), or ECGs demonstrating clinically significant arrhythmias
• Have any other serious systemic disease, including active bacterial or fungal infection, or any medical condition requiring cytotoxic therapy or chronic (at least 4 consecutive weeks) systemic corticosteroid use
• Have active viral hepatitis or symptomatic Human immunodeficiency virus (HIV) infection
• Be breast-feeding, pregnant, or likely to become pregnant during the study
• Known allergic reaction to a prior monoclonal antibody therapy
• Previous treatment with MORAb-004
• Brain metastasis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MORAb-004, 2 mg/kg; Biologic (monoclonal antibody)	Biological: MORAb-004 (monoclonal antibody); Subjects will receive one cycle of treatment with MORAb-004, administered intravenously, on Days 1, 8, 15, and 22 (4 administrations per cycle). Additional cycles will continue without interruption until disease progression occurs or clinical or symptomatic progression as suggested by an investigator.
Experimental: MORAb-004, 4 mg/kg; Biologic (monoclonal antibody)	Biological: MORAb-004 (monoclonal antibody); Subjects will receive one cycle of treatment with MORAb-004, administered intravenously, on Days 1, 8, 15, and 22 (4 administrations per cycle). Additional cycles will continue without interruption until disease progression occurs or clinical or symptomatic progression as suggested by an investigator.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Progression-free Survival (PFS) at Week 24	PFS was defined as the time (in weeks) from the date of randomization to the date of the first sign of disease progression (PD) based on Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, or date of death, regardless of cause. PD greater than or equal to (>=) 20 percent (%) increase in the nadir of total tumor burden (TTB) (minimum 5 millimeter [mm]). Participants who were alive with no disease progression had their PFS time censored at the date of their last tumor assessment. Participants who received a new anti-cancer therapy before disease progression had their PFS time censored at the date of their last tumor assessment before the new anti-cancer therapy was started. PFS was analyzed using Kaplan Meier method.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With PFS at Weeks 16 and 52	PFS was defined as the time (in weeks) from the date of randomization to the date of the first observation of PD (RECIST version 1.1) or date of death, regardless of the cause. PD >=20% increase in the nadir of TTB (minimum 5 mm). Participants who were alive with no disease progression had their PFS time censored at the date of their last tumor assessment. Participants who received new anti-cancer therapy before disease progression had their PFS time censored at the date of their last tumor assessment before the new anti-cancer therapy was initiated. PFS was based on the Kaplan-Meier method.	Week 16 and Week 52
Overall Survival (OS)	OS was defined as the time (in weeks) from the date of randomization to the date of death, regardless of cause. In the absence of death confirmation, or for participants alive at the time of analysis, the survival time was censored at the date of the last study follow-up. OS was calculated using the Kaplan-Meier method. As per planned analysis, efficacy outcomes was planned to be analyzed until cut-off date (02 December 2013).	Date of first study treatment (Day 1) to date of death or up to approximately 2 years 7 months
Percentage of Participants With Overall Response	ORR was defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) that occurred (defined by RECIST version 1.1) using CT/MRI. Per RECIST 1.1, CR= disappearance of all lesions; PR greater than or equal to (>=) 30percent (%) decrease from baseline in TTB. As per planned analysis, efficacy outcomes was planned to be analyzed until cut-off date (02 December 2013).	Date of first study treatment (Day 1) to complete response or partial response, assessed up to approximately 2 years 7 months
Optimal Biologic Dosing (OBD) of Morab-004	OBD is defined as the dose level/exposure level at which three parameters are met: 1) adequate pharmacokinetic (PK) profile with a serum half-life (t1/2) of >=48 hours, 2) at least minimal demonstration of antitumor efficacy (50% or greater PFS rate at 16 weeks), and 3) change of 25% or greater from baseline value in any of the pharmacodynamic (PD) parameters assessed in the study in 30% of participants at that dose level.	Day 1 Cycle 1 (Cycle length = 28 days)

Collaborators and Investigators

• Sponsor: Eisai Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2011
• Primary Completion (Actual): December 2, 2013
• Study Completion (Actual): April 10, 2020

Study Registration Dates

• First Submitted: March 14, 2011
• First Submitted That Met QC Criteria: April 12, 2011
• First Posted (Estimate): April 13, 2011

Study Record Updates

• Last Update Posted (Actual): September 1, 2021
• Last Update Submitted That Met QC Criteria: August 6, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: metastatic; melanoma; malignant
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Antibodies, Monoclonal
• Other Study ID Numbers: MORAb-004-201MEL; 2011-001282-40 (EudraCT Number)