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)
- Conditions
- malignent brain tumorspongioblastoom10029211
- Registration Number
- NL-OMON48548
- Lead Sponsor
- Amgen
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 26
* Written informed consent, subject is at least 18 years of age
* Eastern Cooperative Oncology Group (ECOG, Appendix F) Performance Status of *
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)
* Group 1 subjects must have * 1 index lesion by modified RANO criteria,
exemption: non-measurable disease is allowed for subjects with re-surgery
(surgery for recurrent disease) before start of screening
* Group 2 subjects must have radiographically measurable disease, or
non-measurable disease or both at the time of enrollment are allowedConfirmed
EGFRvIII positivity at time of study enrollment
* Hematological, hepatic and renal function as described in protocol page 35
History or evidence of central nervous system bleeding within 6 months before
enrollment
-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 IP
formulation
-Prior malignancy (other than in situ cancer) unless treated with curative
intent
and without evidence of disease for > 2 years before screening
-Infection requiring intravenous antibiotics that was completed < 1 week of
study
enrollment (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:
-Unresolved toxicities from prior antitumor therapy, defined as not having
resolved
to CTCAE, version 4.0 grade 1
-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 nontopical systemic corticosteroids within 14 days before
enrollment (day 1)
-Major surgery within 7 days of study day 1 with the exception of biopsy and
long
line insertion
-Male and female of reproductive potential who are unwilling to practice an
highly effective method(s) of effective birth control
-Female who is pregnant or lactating/breastfeeding or who plans to be pregnant
or breastfeed
-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.
The following Exclusion Criteria apply in addition for enrollment in
combination cohorts
with AMG 404:
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.
Active or history of any autoimmune disease or immunodeficiencies.
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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Endpoint:<br /><br>* Dose limiting toxicities (DLT), treatment-emergent adverse events,<br /><br>treatment-related adverse events and clinically significant changes in vital<br /><br>signs, physical examinations, and clinical laboratory tests</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary Endpoint(s):<br /><br>* Serum PK parameters for AMG 596 including, but not limited to, average<br /><br>steady-state concentration (Css), area under the concentration-time curve<br /><br>(AUC), clearance, volume of distribution and half-life (t1/2) for serum AMG 596<br /><br>* PK parameters of AMG 404 including, but not limited to, maximum observed<br /><br>serum concentration (Cmax), time to achieve Cmax (tmax) and AUC.<br /><br>** PK parameters for AMG 596 dosed in combination with AMG 404 including, but<br /><br>not limited to, average steady-state concentration (Css), area<br /><br>under the concentration-time curve (AUC), clearance, volume of<br /><br>distribution and half-life (t1/2) for serum AMG 596<br /><br>* Objective response (OR) as per modified RANO, time to response, response<br /><br>duration and time to progression (TTP); progression met AMG 596 monotherapie of<br /><br>AMG 596 in combinatie met AMG 404</p><br>