Clinical Trials /

Study of AMG 596 in Patients With EGFRvIII Positive Glioblastoma

NCT03296696

Description:

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).

Related Conditions:
  • Glioblastoma
  • Malignant Glioma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of AMG 596 in Patients With EGFRvIII Positive Glioblastoma
  • Official Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: 20160132
  • SECONDARY ID: 2017-001658-32
  • NCT ID: NCT03296696

Conditions

  • Glioblastoma or Malignant Glioma

Interventions

DrugSynonymsArms
AMG 596Dose expansion
AMG 404Dose expansion

Purpose

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).

Trial Arms

NameTypeDescriptionInterventions
Dose explorationExperimentalDose exploration of the intervention, AMG 596 alone or in combination with AMG 404
  • AMG 596
  • AMG 404
Dose expansionExperimentalDose expansion of the intervention, AMG 596 alone or in combination with AMG 404
  • AMG 596
  • AMG 404

Eligibility Criteria

        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.
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Subject grade of dose limiting toxicities (DTLs)
Time Frame:12 months
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Average steady-state concentration (Css) for serum AMG 596
Time Frame:12 months
Safety Issue:
Description:
Measure:Area under the concentration-time curve (AUC) for serum AMG 596
Time Frame:12 months
Safety Issue:
Description:
Measure:Clearance for serum AMG 596
Time Frame:12 months
Safety Issue:
Description:
Measure:Volume of distribution for serum AMG 596
Time Frame:12 months
Safety Issue:
Description:
Measure:Half-life (t1/2) for serum AMG 596
Time Frame:12 months
Safety Issue:
Description:
Measure:Maximum abserved serum concentration (Cmax) for AMG 404
Time Frame:12 months
Safety Issue:
Description:
Measure:Time to achieve Cmax (tmax) for AMG 404
Time Frame:12 months
Safety Issue:
Description:
Measure:Area under the concentration-time curve (AUC) for AMG 404
Time Frame:12 months
Safety Issue:
Description:
Measure:Average steady-state concentration (Css) for serum AMG 596 in combination with AMG 404
Time Frame:12 months
Safety Issue:
Description:
Measure:Area under the concentration-time curve (AUC) for serum AMG 596 in combination with AMG 404
Time Frame:12 months
Safety Issue:
Description:
Measure:Clearance for serum AMG 596 in combination with AMG 404
Time Frame:12 months
Safety Issue:
Description:
Measure:Half-life (t1/2) for serum AMG 596 in combination with AMG 404
Time Frame:12 months
Safety Issue:
Description:
Measure:Objective response (OR) as per modified RANO for AMG 596
Time Frame:6 and 12 months
Safety Issue:
Description:Objective response (OR) as per modified RANO (Response Assessment in Neuro-Oncology Criteria).
Measure:Time to response for serum AMG 596 in combination with AMG 404
Time Frame:6 and 12 months
Safety Issue:
Description:
Measure:Response duration for serum AMG 596 in combination with AMG 404
Time Frame:6 and 12 months
Safety Issue:
Description:
Measure:Time to progression (TTP) for serum AMG 596 in combination with AMG 404
Time Frame:6 and 12 months
Safety Issue:
Description:
Measure:Progression free survival (PFS) at 6 and 12 months after treatment initiation with AMG 596 monotherapy
Time Frame:6 and 12 months
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Objective response (OR) as per modified RANO with AMG 596 monotherapy
Time Frame:6 and 12 months
Safety Issue:
Description:
Measure:Time to response with AMG 596 monotherapy
Time Frame:6 and 12 months
Safety Issue:
Description:
Measure:Response duration with AMG 596 monotherapy
Time Frame:6 and 12 months
Safety Issue:
Description:
Measure:Time to progression (TTP) with AMG 596 monotherapy
Time Frame:6 and 12 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Amgen

Trial Keywords

  • Phase 1/1b
  • EGFRvIII-positive glioblastoma or malignant glioma
  • safety and tolerability
  • AMG 596

Last Updated

February 18, 2020