Glioblastoma or Malignant GliomaPhase 1NCT03296696
Study of AMG 596 in Patients With EGFRvIII Positive Glioblastoma
A Phase 1 study testing AMG 596 and AMG 404 in people with Glioblastoma or Malignant Glioma, run by Amgen at 10 sites in 6 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Glioblastoma or Malignant Glioma
- What is being tested?
- AMG 596 and AMG 404
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 10 sitesin 6 countries
- Study dates
- 18 Apr 2018to 28 Aug 2021
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 epidermal growth factor receptor variant III (EGFRvIII) positive tumor
- Must have recurrent disease confirmed by magnetic resonance imaging (MRI) (Group 1) or completed standard of care (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)
Show all 13Show fewer
- 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 Modification of Diet in Renal Disease (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)
Who cannot join
- 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
- Evidence of acute intracranial / intratumoral hemorrhage, except for subjects with stable grade 1 hemorrhage or fresh biopsy
- Known hypersensitivity to immunoglobulins or to any other component of the investigational product (IP) formulation
- Prior malignancy (other than in situ cancer) unless treated with curative intent and without evidence of disease for > 2 years before screening
- 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)
Show all 37Show fewer
- 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 deoxyribonucleic acid (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 ribonucleic acid (RNA) by PCR is necessary. Detectable hepatitis C virus RNA suggests chronic hepatitis C Common terminology criteria for adverse events
- Unresolved toxicities from prior antitumor therapy, defined as not having resolved to common terminology criteria for adverse events (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
- Treatment with non-topical systemic corticosteroids within 14 days before enrollment (day 1) (exemption: prophylactic treatment with dexamethasone as defined in section 6.5, and systemic corticosteroid doses of ≤ 2 mg of dexamethasone (or equivalent) per day after consultation with Sponsor,)
- Prior participation in an investigational study (drug, procedure or device) within 21 days of study day 1
- Major surgery within 7 days of study day 1 with the exception of biopsy and long line insertion
- History or evidence of any other clinically significant disorder, condition or disease that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion
- Male and female of reproductive potential who are unwilling to practice highly effective method(s) of birth control while on study and through 30 days after receiving the last dose of AMG 596 and through 4 months (120 days) after receiving the last dose of AMG 404.
- Criteria for women of non-reproductive potential is as follows:
- Postmenopausal as defined as:
- Age of 55 years with cessation of menses for 12 months or more, OR
- Age < 55 years and no spontaneous menses for at least 2 years, OR
- Age < 55 years and spontaneous menses within the past year, but currently amenorrheic (eg, spontaneous or secondary to chemotherapy) AND with postmenopausal gonadotropin levels (luteinizing hormone and follicle-stimulating hormone level > 40 IU/L) or postmenopausal estradiol levels (< 5 ng/dL) according to the definition of "postmenopausal range" for the laboratory involved; OR
- History of hysterectomy; OR
- History of bilateral oophorectomy
- Highly effective methods of birth control include sexual abstinence (male, female); vasectomy; bilateral tubal ligation/occlusion; hormonal birth control or intrauterine device (IUD) (female).
- Female who is lactating/breastfeeding or who plans to breastfeed while on study through 30 days after receiving the last dose of AMG 596 and through 4 months (120 days) after receiving the last dose of AMG 404.
- Female with a positive pregnancy test.
- Female planning to become pregnant while on study through 30 days after receiving the last dose of AMG 596 and through 4 months (120 days) after receiving the last dose of AMG 404 infusion.
- Male who is unwilling to abstain from sperm donation while on study through 30 days after receiving the last dose of AMG 596 and through 4 months (120 days) after receiving the last dose of AMG 404.
- Subjects likely to not be available to complete all protocol required study visits or procedures, and/or to comply with all required study procedures to the best of the subject and investigator's knowledge.
- History of solid organ transplantation. Prior treatment with anti-PD-1, anti-PD-L1, CTLA-4 or other checkpoint inhibitor drugs
- Prior treatment with AMG 596 monotherapy arm is not eligible to enroll in the combination therapy arm.
- Live vaccine therapies within 4 weeks prior to study drug administration
- Evidence of interstitial lung disease or active, non-infectious pneumonitis
- History of any immune-related colitis. Infectious colitis is allowed if evidence of adequate treatment and clinical recovery exists and at least 3 months interval observed since diagnosis of colitis.
- Active or history of any autoimmune disease or immunodeficiencies. Subjects with Type I diabetes, vitiligo, psoriasis, hypo-or hyper-thyroid disease not requiring immune-suppressive treatment are permitted.
- Myocardial infarction within 6 months of study day 1, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or cardiac arrhythmia requiring medication.
Trial locations and contacts
10 sites in 6 countries.
10 sites in 6 countries
Germany3 sites
Universitätsklinikum Carl Gustav Carus der Technischen Universität Dresden
Dresden, 01307
Universitatsklinikum Hamburg-Eppendorf
Hamburg, 20246
Universitaetsklinikum Wuerzburg
Würzburg, 97080
United States2 sites
University of California Los Angeles
Los Angeles, California, 90024
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Australia2 sites
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000
Royal North SHore Hospital
St Leonards, New South Wales, 2065
Spain1 site
Hospital Universitari Germans Trias i Pujol
Badalona, Cataluña, 08916
About this study
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)
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).
- Conditions
- Glioblastoma or Malignant Glioma
- Being tested
- AMG 596, AMG 404
- Keywords
- Phase 1/1b, EGFRvIII-positive glioblastoma or malignant glioma, safety and tolerability, AMG 596
- Medical subject headings
- Glioblastoma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AMG 596Drug
Drug
AMG 404Drug
Drug
| Study group | Role | What they receive |
|---|---|---|
| Dose exploration | Experimental | Dose exploration of the intervention, AMG 596 alone or in combination with AMG 404 Receives: Drug: AMG 596; Drug: AMG 404 |
| Dose expansion | Experimental | Dose expansion of the intervention, AMG 596 alone or in combination with AMG 404 Receives: Drug: AMG 596; Drug: AMG 404 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose-Limiting Toxicities (DLTs)
A DLT was any of the following occurring and regarded by the investigator as related to AMG 596. Hematological DLTs: absolute neutrophil count (ANC) <0.5×10^9/L for ≥7 days, febrile neutropenia with ANC<0.5×10^9/L and fever ≥38.5°C, platelets<50×10^9/L>7 days or clinically significant bleeding. Non-hematological DLTs: any grade 4 non-hematological toxicity, any grade ≥3 non-hematological toxicity if nausea and vomiting, grade 3 non-hematologic toxicity lasting >3 days despite treatment, grade 3 fatigue wasn't classified as DLT, grade 3 acute kidney injury, grade 3 seizure, ataxia, encephalopathy, other grade 3 neurologic-related adverse events lasting >3 days despite treatment, neurologic-related adverse event leading to treatment interruption needing>1 week to resolve to grade≤1, any grade 3 endocrinopathy that can't be controlled by hormonal replacement. Toxicity grading was graded using the Common Terminology Criteria for Adverse Events (CTCAE v4.0)
Measured: Up to 28 days
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
An adverse event (AE) was defined as any untoward medical occurrence in a clinical trial participant. A TEAE was any AE that begun or worsened after the initial dose of investigational product. Any clinically significant changes in vital signs, physical examinations, and clinical laboratory tests that begun or worsened after the initial dose of investigational product were recorded as TEAEs.
Measured: First dose of study drug until 37 days after last dose or end of study, whichever is earlier. Duration with median (min, max) in months: 3.32 (1.28, 29.31)
Number of Participants With Treatment-Related Adverse Events (AEs)
A treatment-related AE was defined as any untoward medical occurrence in a clinical trial participant that was considered related to the investigational product. Any clinically significant changes in vital signs, physical examinations, and clinical laboratory tests that were considered related to the investigational product were recorded as treatment-related AEs.
Measured: First dose of study drug until 37 days after last dose or end of study, whichever is earlier. Duration with median (min, max) in months: 3.32 (1.28, 29.31)
Secondary outcomes (10)
Average Steady-state Concentration (Css) of Serum AMG 596
Measured: Cycle1 to Cycle2 (cycle=14 days in single participant cohorts,42 days in multiple participant cohorts):7-days on/7-days off dosing and 28-days on/14-days off dosing:pre-infusion,2,6,8,24,48hrs post-infusion start,0.5,2,4,8,24hrs post infusion end
Area Under the Concentration-time Curve (AUC) for Serum AMG 596
There were insufficient evaluable samples collected for the determination of AUC.
Measured: Cycle1 to Cycle2 (cycle=14 days in single participant cohorts,42 days in multiple participant cohorts):7-days on/7-days off dosing and 28-days on/14-days off dosing:pre-infusion,2,6,8,24,48hrs post-infusion start,0.5,2,4,8,24hrs post infusion end
Clearance for Serum AMG 596
Clearance (CL) is calculated based on dose and AUC.
Measured: Cycle1 to Cycle2 (cycle=14 days in single participant cohorts,42 days in multiple participant cohorts):7-days on/7-days off dosing and 28-days on/14-days off dosing:pre-infusion,2,6,8,24,48hrs post-infusion start,0.5,2,4,8,24hrs post infusion end
Apparent Volume of Distribution at Steady-State for Serum AMG 596
The formula for volume of distribution is dose/concentration. For this study, the dose is measured in mcg/day and concentration is measure as ng/mL resulting in units of mcg/day/(ng/mL) for volume of distribution.
Measured: Cycle1 to Cycle2 (cycle=14 days in single participant cohorts,42 days in multiple participant cohorts):7-days on/7-days off dosing and 28-days on/14-days off dosing:pre-infusion,2,6,8,24,48hrs post-infusion start,0.5,2,4,8,24hrs post infusion end
Terminal Half-life (t1/2) Associated With Lambda z (λz) for Serum AMG 596
Measured: Cycle1 to Cycle2 (cycle=14 days in single participant cohorts,42 days in multiple participant cohorts):7-days on/7-days off dosing and 28-days on/14-days off dosing:pre-infusion,2,6,8,24,48hrs post-infusion start,0.5,2,4,8,24hrs post infusion end
Number of Participants With an Objective Response (OR) Per Modified Response Assessment in Neuro-Oncology Criteria (RANO) Criteria With AMG 596 Monotherapy
Objective response was defined as the number of participants with complete response (CR) or partial response (PR) per modified RANO criteria. CR per modified RANO: disappearance of all enhancing disease, no new lesions, stable or improved T2-weighted fluid-attenuated inversion recovery (T2/FLAIR), no more than physiological steroids, clinically stable or improved, disappearance confirmed with follow-up scans after ≥4 weeks. PR per modified RANO: ≥50% decrease in the sum of perpendicular diameters of enhancing disease from baseline, stable or improved T2/FLAIR, stable or decreased steroid dose, clinically stable or improved, decrease confirmed with follow up scan after ≥ 4 weeks.
Measured: Baseline up to 12 Months
Time to Response With AMG 596 Monotherapy
Time to response was calculated as the number of months from the date of first administration of AMG 596 to the date of confirmation of first objective response per magnetic resonance imaging (MRI) scan. If a participant did not respond, time to response was censored at the date of the last evaluable response assessment.
Measured: Up to 12 months
Response Duration With AMG 596 Monotherapy
Response duration was analysed as the number of months between the first tumor response assessment of an OR (PR or CR) which is subsequently confirmed to the time of the first tumor response assessment of progressive disease or death if due to disease progression.
Measured: Up to 30 months
Time to Progression (TTP) With AMG 596 Monotherapy
The TTP was calculated as the time from the date of first dose of AMG 596 until the date of diagnosis of progression of tumor. Participants who did not have progression were censored at the last radiological non-missing evaluable tumor assessment date.
Measured: Up to 12 Months
Progression-free Survival (PFS) With AMG 596 Monotherapy
The PFS was calculated as the time from the date of first dose of AMG 596 until the date of diagnosis of progression of tumor, or date of death, whichever was earlier.
Measured: Up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2017
- Study start18 Apr 2018
- Primary completion1 Jul 2021
- Study completion28 Aug 2021
Why it stopped: Amgen business decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Glioblastoma or Malignant GliomaStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Bayesian logistic regression model
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03296696
- Sponsor's protocol ID
- 20160132
- Other IDs
- 2017-001658-32, 2017
- Status last verified
- Oct 2024
- First submitted
- 18 Sep 2017
- Last updated
- 29 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
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.
PubMed 33632870
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03296696
- Acronym / sponsor ID
- 20160132
- Conditions
- Glioblastoma or Malignant Glioma
- Keywords
- Phase 1/1b, EGFRvIII-positive glioblastoma or malignant glioma, safety and tolerability, AMG 596
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Amgen business decision
- Enrolment
- 30 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 18 Apr 2018 (actual)
- Primary completion
- 1 Jul 2021 (actual)
- Study completion
- 28 Aug 2021 (actual)
- First posted
- 28 Sep 2017 (actual)
- Results
- Posted 29 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Bayesian logistic regression model
| Arm | Type | Receives |
|---|---|---|
| Dose exploration | Experimental | Drug: AMG 596, Drug: AMG 404Dose exploration of the intervention, AMG 596 alone or in combination with AMG 404 |
| Dose expansion | Experimental | Drug: AMG 596, Drug: AMG 404Dose expansion of the intervention, AMG 596 alone or in combination with AMG 404 |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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 epidermal growth factor receptor variant III (EGFRvIII) positive tumor
- Must have recurrent disease confirmed by magnetic resonance imaging (MRI) (Group 1) or completed standard of care (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:
Key exclusion criteria (37 listed)
- 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
- Evidence of acute intracranial / intratumoral hemorrhage, except for subjects with stable grade 1 hemorrhage or fresh biopsy
- Known hypersensitivity to immunoglobulins or to any other component of the investigational product (IP) formulation
- Prior malignancy (other than in situ cancer) unless treated with curative intent and without evidence of disease for > 2 years before screening
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AMG 596Drug | Drug | Dose expansion, Dose exploration |
| AMG 404Drug | Drug | Dose expansion, Dose exploration |
Primary outcome
Number of Participants With Dose-Limiting Toxicities (DLTs)
Time frame: Up to 28 days
A DLT was any of the following occurring and regarded by the investigator as related to AMG 596. Hematological DLTs: absolute neutrophil count (ANC) <0.5×10^9/L for ≥7 days, febrile neutropenia with ANC<0.5×10^9/L and fever ≥38.5°C, platelets<50×10^9/L>7 days or clinically significant bleeding. Non-hematological DLTs: any grade 4 non-hematological toxicity, any grade ≥3 non-hematological toxicity if nausea and vomiting, grade 3 non-hematologic toxicity lasting >3 days despite treatment, grade 3 fatigue wasn't classified as DLT, grade 3 acute kidney injury, grade 3 seizure, ataxia, encephalopathy, other grade 3 neurologic-related adverse events lasting >3 days despite treatment, neurologic-related adverse event leading to treatment interruption needing>1 week to resolve to grade≤1, any grade 3 endocrinopathy that can't be controlled by hormonal replacement. Toxicity grading was graded using the Common Terminology Criteria for Adverse Events (CTCAE v4.0)
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Time frame: First dose of study drug until 37 days after last dose or end of study, whichever is earlier. Duration with median (min, max) in months: 3.32 (1.28, 29.31)
An adverse event (AE) was defined as any untoward medical occurrence in a clinical trial participant. A TEAE was any AE that begun or worsened after the initial dose of investigational product. Any clinically significant changes in vital signs, physical examinations, and clinical laboratory tests that begun or worsened after the initial dose of investigational product were recorded as TEAEs.
Number of Participants With Treatment-Related Adverse Events (AEs)
Time frame: First dose of study drug until 37 days after last dose or end of study, whichever is earlier. Duration with median (min, max) in months: 3.32 (1.28, 29.31)
A treatment-related AE was defined as any untoward medical occurrence in a clinical trial participant that was considered related to the investigational product. Any clinically significant changes in vital signs, physical examinations, and clinical laboratory tests that were considered related to the investigational product were recorded as treatment-related AEs.
10 secondary outcomes
Average Steady-state Concentration (Css) of Serum AMG 596
Time frame: Cycle1 to Cycle2 (cycle=14 days in single participant cohorts,42 days in multiple participant cohorts):7-days on/7-days off dosing and 28-days on/14-days off dosing:pre-infusion,2,6,8,24,48hrs post-infusion start,0.5,2,4,8,24hrs post infusion end
Area Under the Concentration-time Curve (AUC) for Serum AMG 596
Time frame: Cycle1 to Cycle2 (cycle=14 days in single participant cohorts,42 days in multiple participant cohorts):7-days on/7-days off dosing and 28-days on/14-days off dosing:pre-infusion,2,6,8,24,48hrs post-infusion start,0.5,2,4,8,24hrs post infusion end
Clearance for Serum AMG 596
Time frame: Cycle1 to Cycle2 (cycle=14 days in single participant cohorts,42 days in multiple participant cohorts):7-days on/7-days off dosing and 28-days on/14-days off dosing:pre-infusion,2,6,8,24,48hrs post-infusion start,0.5,2,4,8,24hrs post infusion end
Apparent Volume of Distribution at Steady-State for Serum AMG 596
Time frame: Cycle1 to Cycle2 (cycle=14 days in single participant cohorts,42 days in multiple participant cohorts):7-days on/7-days off dosing and 28-days on/14-days off dosing:pre-infusion,2,6,8,24,48hrs post-infusion start,0.5,2,4,8,24hrs post infusion end
Terminal Half-life (t1/2) Associated With Lambda z (λz) for Serum AMG 596
Time frame: Cycle1 to Cycle2 (cycle=14 days in single participant cohorts,42 days in multiple participant cohorts):7-days on/7-days off dosing and 28-days on/14-days off dosing:pre-infusion,2,6,8,24,48hrs post-infusion start,0.5,2,4,8,24hrs post infusion end
Number of Participants With an Objective Response (OR) Per Modified Response Assessment in Neuro-Oncology Criteria (RANO) Criteria With AMG 596 Monotherapy
Time frame: Baseline up to 12 Months
Time to Response With AMG 596 Monotherapy
Time frame: Up to 12 months
Response Duration With AMG 596 Monotherapy
Time frame: Up to 30 months
Time to Progression (TTP) With AMG 596 Monotherapy
Time frame: Up to 12 Months
Progression-free Survival (PFS) With AMG 596 Monotherapy
Time frame: Up to 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 33632870Sternjak 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.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
10 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AMG 596 and AMG 404 in people with Glioblastoma or Malignant Glioma, run by Amgen at 10 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 29 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Germany, United States, Australia, France, Netherlands and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose-Limiting Toxicities (DLTs) (time frame: Up to 28 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03296696, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2024.