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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03296696




Registration number
NCT03296696
Ethics application status
Date submitted
18/09/2017
Date registered
28/09/2017
Date last updated
16/06/2020

Titles & IDs
Public title
Study of AMG 596 in Patients With EGFRvIII Positive Glioblastoma
Scientific 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)
Secondary ID [1] 0 0
2017-001658-32
Secondary ID [2] 0 0
20160132
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Glioblastoma or Malignant Glioma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AMG 596
Treatment: Drugs - AMG 404

Experimental: Dose exploration - Dose exploration of the intervention, AMG 596 alone or in combination with AMG 404

Experimental: Dose expansion - Dose expansion of the intervention, AMG 596 alone or in combination with AMG 404


Treatment: Drugs: AMG 596
Drug

Treatment: Drugs: AMG 404
Drug

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Subject grade of dose limiting toxicities (DTLs) - 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
Timepoint [1] 0 0
12 months
Primary outcome [2] 0 0
Number of subject with treatment-emergent adverse events
Timepoint [2] 0 0
12 months
Primary outcome [3] 0 0
Number of subjects with treatment-related adverse events
Timepoint [3] 0 0
12 months
Primary outcome [4] 0 0
Number of subjects with clinically significant changes in vital signs
Timepoint [4] 0 0
12 months
Primary outcome [5] 0 0
Number of subjects with clinically significant changes in physical examinations
Timepoint [5] 0 0
12 months
Primary outcome [6] 0 0
Number of subjects with clinically significant changes in clinical laboratory tests
Timepoint [6] 0 0
12 months
Secondary outcome [1] 0 0
Average steady-state concentration (Css) for serum AMG 596
Timepoint [1] 0 0
12 months
Secondary outcome [2] 0 0
Area under the concentration-time curve (AUC) for serum AMG 596
Timepoint [2] 0 0
12 months
Secondary outcome [3] 0 0
Clearance for serum AMG 596
Timepoint [3] 0 0
12 months
Secondary outcome [4] 0 0
Volume of distribution for serum AMG 596
Timepoint [4] 0 0
12 months
Secondary outcome [5] 0 0
Half-life (t1/2) for serum AMG 596
Timepoint [5] 0 0
12 months
Secondary outcome [6] 0 0
Maximum abserved serum concentration (Cmax) for AMG 404
Timepoint [6] 0 0
12 months
Secondary outcome [7] 0 0
Time to achieve Cmax (tmax) for AMG 404
Timepoint [7] 0 0
12 months
Secondary outcome [8] 0 0
Area under the concentration-time curve (AUC) for AMG 404
Timepoint [8] 0 0
12 months
Secondary outcome [9] 0 0
Average steady-state concentration (Css) for serum AMG 596 in combination with AMG 404
Timepoint [9] 0 0
12 months
Secondary outcome [10] 0 0
Area under the concentration-time curve (AUC) for serum AMG 596 in combination with AMG 404
Timepoint [10] 0 0
12 months
Secondary outcome [11] 0 0
Clearance for serum AMG 596 in combination with AMG 404
Timepoint [11] 0 0
12 months
Secondary outcome [12] 0 0
Half-life (t1/2) for serum AMG 596 in combination with AMG 404
Timepoint [12] 0 0
12 months
Secondary outcome [13] 0 0
Objective response (OR) as per modified RANO for AMG 596 - Objective response (OR) as per modified RANO (Response Assessment in Neuro-Oncology Criteria).
Timepoint [13] 0 0
6 and 12 months
Secondary outcome [14] 0 0
Time to response for serum AMG 596 in combination with AMG 404
Timepoint [14] 0 0
6 and 12 months
Secondary outcome [15] 0 0
Response duration for serum AMG 596 in combination with AMG 404
Timepoint [15] 0 0
6 and 12 months
Secondary outcome [16] 0 0
Time to progression (TTP) for serum AMG 596 in combination with AMG 404
Timepoint [16] 0 0
6 and 12 months
Secondary outcome [17] 0 0
Progression free survival (PFS) at 6 and 12 months after treatment initiation with AMG 596 monotherapy
Timepoint [17] 0 0
6 and 12 months
Secondary outcome [18] 0 0
Progression free survival (PFS) at 6 and 12 months after treatment initiation with AMG 596 in combination with AMG 404
Timepoint [18] 0 0
6 and 12 months
Secondary outcome [19] 0 0
Objective response (OR) as per modified RANO with AMG 596 monotherapy
Timepoint [19] 0 0
6 and 12 months
Secondary outcome [20] 0 0
Time to response with AMG 596 monotherapy
Timepoint [20] 0 0
6 and 12 months
Secondary outcome [21] 0 0
Response duration with AMG 596 monotherapy
Timepoint [21] 0 0
6 and 12 months
Secondary outcome [22] 0 0
Time to progression (TTP) with AMG 596 monotherapy
Timepoint [22] 0 0
6 and 12 months

Eligibility
Key inclusion 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)
Minimum age
18 Years
Maximum age
100 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Research Site - St. Leonards
Recruitment hospital [2] 0 0
Research Site - Melbourne
Recruitment postcode(s) [1] 0 0
2065 - St. Leonards
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
New York
Country [3] 0 0
France
State/province [3] 0 0
Villejuif
Country [4] 0 0
Germany
State/province [4] 0 0
Dresden
Country [5] 0 0
Germany
State/province [5] 0 0
Hamburg
Country [6] 0 0
Germany
State/province [6] 0 0
Würzburg
Country [7] 0 0
Netherlands
State/province [7] 0 0
Amsterdam
Country [8] 0 0
Spain
State/province [8] 0 0
Cataluña

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/show/NCT03296696
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Amgen Call Center
Address 0 0
Country 0 0
Phone 0 0
866-572-6436
Fax 0 0
Email 0 0
medinfo@amgen.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03296696