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Study of AMG 596 in Patients With EGFRvIII Positive Glioblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03296696
Recruitment Status : Active, not recruiting
First Posted : September 28, 2017
Last Update Posted : June 4, 2021
Sponsor:
Information provided by (Responsible Party):
Amgen

Tracking Information
First Submitted Date  ICMJE September 18, 2017
First Posted Date  ICMJE September 28, 2017
Last Update Posted Date June 4, 2021
Actual Study Start Date  ICMJE April 18, 2018
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 18, 2020)
  • Subject grade of dose limiting toxicities (DTLs) [ Time Frame: 12 months ]
    Subject grade of dose limiting toxicities is the occurrence of any of the toxicities during the DLT evaluation period if judged by the investigator to be related to the administration of AMG 596 and AMG 404
  • Number of subject with treatment-emergent adverse events [ Time Frame: 12 months ]
  • Number of subjects with treatment-related adverse events [ Time Frame: 12 months ]
  • Number of subjects with clinically significant changes in vital signs [ Time Frame: 12 months ]
  • Number of subjects with clinically significant changes in physical examinations [ Time Frame: 12 months ]
  • Number of subjects with clinically significant changes in clinical laboratory tests [ Time Frame: 12 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 27, 2017)
Number of subject with treatment-emergent adverse events [ Time Frame: 12 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 18, 2020)
  • Average steady-state concentration (Css) for serum AMG 596 [ Time Frame: 12 months ]
  • Area under the concentration-time curve (AUC) for serum AMG 596 [ Time Frame: 12 months ]
  • Clearance for serum AMG 596 [ Time Frame: 12 months ]
  • Volume of distribution for serum AMG 596 [ Time Frame: 12 months ]
  • Half-life (t1/2) for serum AMG 596 [ Time Frame: 12 months ]
  • Maximum abserved serum concentration (Cmax) for AMG 404 [ Time Frame: 12 months ]
  • Time to achieve Cmax (tmax) for AMG 404 [ Time Frame: 12 months ]
  • Area under the concentration-time curve (AUC) for AMG 404 [ Time Frame: 12 months ]
  • Average steady-state concentration (Css) for serum AMG 596 in combination with AMG 404 [ Time Frame: 12 months ]
  • Area under the concentration-time curve (AUC) for serum AMG 596 in combination with AMG 404 [ Time Frame: 12 months ]
  • Clearance for serum AMG 596 in combination with AMG 404 [ Time Frame: 12 months ]
  • Half-life (t1/2) for serum AMG 596 in combination with AMG 404 [ Time Frame: 12 months ]
  • Objective response (OR) as per modified RANO for AMG 596 [ Time Frame: 6 and 12 months ]
    Objective response (OR) as per modified RANO (Response Assessment in Neuro-Oncology Criteria).
  • Time to response for serum AMG 596 in combination with AMG 404 [ Time Frame: 6 and 12 months ]
  • Response duration for serum AMG 596 in combination with AMG 404 [ Time Frame: 6 and 12 months ]
  • Time to progression (TTP) for serum AMG 596 in combination with AMG 404 [ Time Frame: 6 and 12 months ]
  • Progression free survival (PFS) at 6 and 12 months after treatment initiation with AMG 596 monotherapy [ Time Frame: 6 and 12 months ]
  • Progression free survival (PFS) at 6 and 12 months after treatment initiation with AMG 596 in combination with AMG 404 [ Time Frame: 6 and 12 months ]
  • Objective response (OR) as per modified RANO with AMG 596 monotherapy [ Time Frame: 6 and 12 months ]
  • Time to response with AMG 596 monotherapy [ Time Frame: 6 and 12 months ]
  • Response duration with AMG 596 monotherapy [ Time Frame: 6 and 12 months ]
  • Time to progression (TTP) with AMG 596 monotherapy [ Time Frame: 6 and 12 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 27, 2017)
  • Objective response (OR) as per modified RANO [ Time Frame: 12 month ]
    Objective response (OR) as per modified RANO (Response Assessment in Neuro-Oncology Criteria).
  • Area under the concentration-time curve (AUC) for serum AMG 596 [ Time Frame: cycle length up to 6 weeks ]
  • Volume of distribution for serum AMG 596 [ Time Frame: cycle length up to 6 weeks ]
  • Average steady-state concentration (Css) for serum AMG 596 [ Time Frame: cycle length up to 6 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of AMG 596 in Patients With EGFRvIII Positive Glioblastoma
Official Title  ICMJE Phase 1/1b Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 596 as Monotherapy and in Combination With AMG 404 in Subjects With Glioblastoma or Malignant Glioma Expressing Mutant Epidermal Growth Factor Receptor Variant III (EGFRvIII)
Brief Summary

This is a Phase 1/1b Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 596 monotherapy or in combination with AMG 404 in Subjects with Glioblastoma or Malignant Glioma Expressing Mutant Epidermal Growth Factor Receptor Variant III (EGFRvIII).

This is a first in human (FIH), open-label, sequential-dose-escalation study in subjects with EGFRvIII-positive glioblastoma or malignant glioma. This study will enroll 2 groups of subjects according to disease stage, recurrent disease (Group 1) and maintenance treatment after SoC in newly diagnosed disease (Group 2).

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
Bayesian logistic regression model
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Glioblastoma or Malignant Glioma
Intervention  ICMJE
  • Drug: AMG 596
    Drug
  • Drug: AMG 404
    Drug
Study Arms  ICMJE
  • Experimental: Dose exploration
    Dose exploration of the intervention, AMG 596 alone or in combination with AMG 404
    Interventions:
    • Drug: AMG 596
    • Drug: AMG 404
  • Experimental: Dose expansion
    Dose expansion of the intervention, AMG 596 alone or in combination with AMG 404
    Interventions:
    • Drug: AMG 596
    • Drug: AMG 404
Publications * Sternjak A, Lee F, Thomas O, Balazs M, Wahl J, Lorenczewski G, Ullrich I, Muenz M, Rattel B, Bailis JM, Friedrich M. Preclinical Assessment of AMG 596, a Bispecific T-cell Engager (BiTE) Immunotherapy Targeting the Tumor-specific Antigen EGFRvIII. Mol Cancer Ther. 2021 May;20(5):925-933. doi: 10.1158/1535-7163.MCT-20-0508. Epub 2021 Feb 25.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: July 7, 2020)
30
Original Estimated Enrollment  ICMJE
 (submitted: September 27, 2017)
82
Estimated Study Completion Date  ICMJE December 31, 2021
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

  • Eastern Cooperative Oncology Group (ECOG, Appendix G) Performance Status of less than or equal to 1
  • Life expectancy of at least 3 months, in the opinion of the investigator.
  • Must have pathologically documented, and definitively diagnosed World Health Organization (WHO) grade 4, glioblastoma or lower grade malignant gliomas with EGFRvIII positive tumor
  • Must have recurrent disease confirmed by MRI (Group 1) or completed SoC therapy such as surgery with adjuvant radiochemotherapy with or without maintenance temozolomide according to local standards for newly diagnosed disease (Group 2)
  • Hematological function as follows:

    • Absolute neutrophil count (ANC) greater than 1500/mm3 (1.5 × 10 9/L)
    • Platelet count greater than 100,000 mm3 (100 × 10 9/L)
    • White blood cell (WBC) count greater than 3 × 10 9/L
    • Hemoglobin greater than 9.0 g/dL
  • Renal function as follows: serum creatinine less than 2.0 mg/dL and estimated glomerular filtration rate greater than or equal to 60 mL/min/1.73 m2 by MDRD and urine protein quantitative value of less than 30 mg/dL in urinalysis or less than or equal to 1+ on dipstick
  • Hepatic function as follows:

    • Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) less than or equal to 3.0 x upper limit of normal (ULN)
    • Bilirubin less than or equal to 1.5 x ULN (unless considered due to Gilbert's syndrome or hemolysis)

Exclusion Criteria

  • History or evidence of central nervous system bleeding as defined by stroke or intraocular bleed (including embolic stroke) not associated with any antitumor surgery within 6 months before enrolment
  • Known hypersensitivity to immunoglobulins or to any other component of the IP formulation
  • Active infection requiring intravenous antibiotics that was completed less than 1 week of study enrolment (day 1) with the exemption of prophylactic antibiotics for long line insertion or biopsy
  • Known positive test for human immunodeficiency virus (HIV)
  • Active hepatitis B and C based on the following results:

    • Positive for hepatitis B surface antigen (HepBsAg) (indicative of chronic hepatitis B or recent acute hepatitis B)
    • Negative HepBsAg and positive for hepatitis B core antibody: hepatitis B virus DNA by polymerase chain reaction (PCR) is necessary. Detectable hepatitis B virus DNA suggests occult hepatitis B
    • Positive hepatitis C virus antibody (HepCAb): hepatitis C virus RNA by PCR is necessary. Detectable hepatitis C virus RNA suggests chronic hepatitis C
  • Unresolved toxicities from prior antitumor therapy, defined as not having resolved to CTCAE, version 4.0 grade 1 (with the exception of myelosuppression, eg, neutropenia, anemia, thrombocytopenia), or to levels dictated in the eligibility criteria with the exception of alopecia or toxicities from prior antitumor therapy that are considered irreversible (defined as having been present and stable for greater than 2 months) which may be allowed if they are not otherwise described in the exclusion criteria AND there is agreement to allow by both the investigator and sponsor
  • Antitumor therapy (chemotherapy, antibody therapy, molecular-targeted therapy, or investigational agent) within 14 days (Group 2 subjects) or 5 half-lives (whichever is longer: for Group 1 subjects) of day 1. Avastin, Pembrolizumab must be stopped 14 days prior to day 1
  • Female with a positive pregnancy test.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   France,   Germany,   Netherlands,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03296696
Other Study ID Numbers  ICMJE 20160132
2017-001658-32 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
URL: https://www.amgen.com/datasharing
Responsible Party Amgen
Study Sponsor  ICMJE Amgen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: MD Amgen
PRS Account Amgen
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP