An Efficacy Study of MORAb-009 (Amatuximab) in Subjects With Pleural Mesothelioma (Amatuximab)

An Open-Label Clinical Trial of MORAb-009 in Combination With Pemetrexed and Cisplatin in Subjects With Mesothelioma

This research is being done to find out if pemetrexed and cisplatin work better when given together with an experimental drug called MORAb-009 in patients with malignant pleural mesothelioma.

Study Overview

• Status: Completed
• Conditions: Malignant Pleural Mesothelioma
• Intervention / Treatment: Drug: MORAb-009 (Amatuximab); Drug: Pemetrexed; Drug: Cisplatin

• Study Type: Interventional
• Enrollment (Actual): 89
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec, PQ, Canada, G1V 3E6
    • Hôpital Laval
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital
• Germany
  • Berlin, Germany, 14165
    • Helios Klinikum Emil Von Behring
  • Gauting, Germany, 82131
    • Asklepios Fachkliniken Müchen-Gauting
  • Großhansdorf, Germany, 22927
    • Krankenhaus Großhansdorf
  • Hamburg, Germany, 21075
    • Asklepios Klinik Harburg
  • Hannover, Germany, 30625
    • Medizinsche Hochschule Hannover
  • Immenhausen, Germany, 34376
    • Fachklinik für Lungenerkrankungen Immenhausen
  • München, Germany, 81657
    • Medizinische Klinik (Hämatologie/Onkologie)
• Netherlands
  • Enschede, Netherlands, 7513 ER
    • Medisch Spectrum Twente
  • Rotterdam, Netherlands, 3015 CE
    • Erasmus MC
• Spain
  • Barcelona, Spain, 08025
    • H. de La Santa Creu I Sant Pau
  • Barcelona, Spain, 08208
    • Consorci Sanitari Parc Taulí
  • Palma de Mallorca, Spain, 07014
    • H. Son Dureta
  • Pamplona, Spain, 31008
    • Clinica Universitaria De Navarra
  • Sevilla, Spain, 41013
    • H. Virgen del Rocío
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama, Birmingham
  • California
    • La Jolla, California, United States, 92093
      • University of California, San Diego
    • Los Angeles, California, United States, 90095
      • UCLA Medical Hematology & Oncology
    • San Francisco, California, United States, 94115
      • University of California, San Francisco
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center
  • Delaware
    • Newark, Delaware, United States, 19713
      • Christiana Care Health System
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Johns Hopkins University--Sidney Kimmel Comprehensive Cancer Center
    • Bethesda, Maryland, United States, 20892
      • NIH/National Cancer Institute
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Mary Babb Randolph Cancer Center

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

Primary Inclusion Criteria:

• Confirmed diagnosis of malignant pleural mesothelioma (MPM) with the following characteristics: unresectable disease (or otherwise not a candidate for curative surgery); epithelial type or biphasic (mixed) type with low sarcomatous content.
• Measurable disease at Screening by computed tomography (CT)(or magnetic resonance imaging [MRI]).
• KPS of greater than or equal to 70% at Screening.
• Life expectancy of at least 3 months

Primary Exclusion Criteria:

• Sarcomatous type of mesothelioma
• Prior systemic therapy or radiotherapy for MPM; local radiotherapy for symptom control (ie, non-curative intent) is permitted.
• Confirmed presence of CNS tumor involvement.
• Evidence of other active malignancy requiring treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open Label; Pemetrexed, Cisplatin and MORAb-009 (Amatuximab)	Drug: MORAb-009 (Amatuximab); MORAb-009 (Amatuximab) by IV on Days 1 and 8 every 21 days for 6 cycles.; Drug: Pemetrexed; Pemetrexed 500 mg/m2 on Day 1 of each 21-day cycle for 6 cycles; Drug: Cisplatin; Cisplatin 75 mg/m2 on Day 1 of each 21-day cycle for 6 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Progression Free Survival (PFS) Responders and Non-responders at Month 6	Number of participants with PFS responders and non-responders at Month 6 was reported. PFS was defined as the time from the date of the first dose of amatuximab to the date of disease progression or death due to any cause, as determined by independent radiologist based on the modified Response Evaluation Criteria in Solid Tumors (RECIST) utilizing the total tumor measurement (performed by computerized tomography (CT)/magnetic resonance imaging (MRI)) which includes the pleural unidimensional measure plus the total of the target lesion(s) measurement. A "response", in terms of PFS, was defined to be at least a 6-month stabilization of disease. Progressive disease (PD) as measured by Modified RECIST was defined as an increase of at least 20 percent (%) in the total tumor measurement over the nadir measurement, or the appearance of one or more new lesions.	Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	ORR, defined as the percentage of participants with objective evidence of complete response (CR) or partial response (PR) as determined by independent radiologist based on the modified RECIST utilizing the total tumor measurement (performed by CT/ MRI) which includes the pleural unidimensional measure plus the total of the target lesion(s) measurement. Tumor assessments performed up to the initiation of further anticancer therapy were considered. CR was defined as the disappearance of all target lesions with no evidence of tumor elsewhere, and PR was defined as at least a 30% reduction in the total tumor measurement. A confirmed response required a repeat observation on two occasions 4 weeks apart. ORR = CR + PR.	From the date of first dose until evidence of CR or PR, up to approximately 5 years
Duration of Response (DR)	DR was derived for those participants who achieved a PFS Response and had an objective evidence of CR or PR. DR was defined as the time (in months) from first documentation of objective response (CR or PR) to the first documentation of disease progression or death [as determined by independent radiologist based on the modified RECIST utilizing the total tumor measurement (performed by CT/ MRI) which includes the pleural unidimensional measure plus the total of the target lesion(s) measurement]. Tumor assessments performed up to the initiation of further anticancer therapy were considered. CR was defined as the disappearance of all target lesions with no evidence of tumor elsewhere, and PR was defined as at least a 30% reduction in the total tumor measurement. PD as measured by Modified RECIST was defined as an increase of at least 20% in the total tumor measurement over the nadir measurement, or the appearance of one or more new lesions.	From the first documentation of objective response (CR or PR) to the first documentation of disease progression, up to approximately 5 years
Time to Tumor Response (TTR)	TTR was derived for those participants with objective evidence of CR or PR. TTR was defined as the time from the date of the first dose of amatuximab to first documentation of objective tumor response. CR was defined as the disappearance of all target lesions with no evidence of tumor elsewhere, and PR was defined as at least a 30% reduction in the total tumor measurement.	From the date of the first dose to first documentation of objective response, up to approximately 5 years
Overall Survival (OS)	OS was defined as the time from the date of the first dose of amatuximab to the date of death.	From the date of first dose to the date of death, up to approximately 5 years
Overall Progression Free Survival	Overall PFS was defined as the time from the date of first dose of amatuximab to the date of disease progression or death due to any cause. In the absence of confirmation of death, the survival time was censored at the date of the last follow-up contact. Tumor assessments performed up to the initiation of further anticancer therapy were considered. PD as measured by Modified RECIST was defined as an increase of at least 20% in the total tumor measurement over the nadir measurement, or the appearance of one or more new lesions.	From the date of first dose of amatuximab to the date of disease progression, up to approximately 5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Amatuximab	An adverse event (AE) was any untoward medical occurrence (example; any unfavorable and unintended sign including abnormal laboratory findings, symptom or disease) in a participant or clinical investigation participant after providing written informed consent for participation in the study until the end of study visit. TEAEs were defined as an AE that developed or worsened in severity during the on-treatment period (from first dose of amatuximab to 30 days after last dose of amatuximab). SAE was defined as any adverse event (appearance of [or worsening of any pre-existing]) undesirable sign, symptom or medical conditions which is fatal or life-threatening or results in persistent or significant disability/incapacity or constitutes a congenital anomaly/birth defect or requires inpatient hospitalization or prolongation of existing hospitalization or is medically significant.	From date of first dose of study drug up to 30 days after the last dose of study treatment, up to approximately 5 years

Collaborators and Investigators

• Sponsor: Morphotek
• Investigators: Study Director: Bruce Wallin, MD, Morphotek

Study record dates

Study Major Dates

• Study Start (Actual): December 31, 2008
• Primary Completion (Actual): June 30, 2011
• Study Completion (Actual): January 10, 2014

Study Registration Dates

• First Submitted: August 19, 2008
• First Submitted That Met QC Criteria: August 19, 2008
• First Posted (Estimate): August 20, 2008

Study Record Updates

• Last Update Posted (Actual): September 22, 2022
• Last Update Submitted That Met QC Criteria: August 24, 2022
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Adenoma; Neoplasms, Mesothelial; Pleural Neoplasms; Mesothelioma; Mesothelioma, Malignant; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Folic Acid Antagonists; Pemetrexed
• Other Study ID Numbers: MORAb-009-003 Amatuximab; 2008-005448-18 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No