Inclusion Criteria:
- - The patient has provided written informed consent prior to any study-related
procedure.
- - Newly diagnosed glioblastoma or gliosarcoma as confirmed by local histopathology.
- - The patient is at least 18 years of age on day of signing informed consent.
- - Absence of isocitrate dehydrogenase (IDH)1 R132H mutation by immunohistochemistry.
- - A maximum dose of 4 mg/day dexamethasone or equivalent doses for other
corticosteroids, which has been stable or decreased for ≥5 days prior to start of
radiotherapy.
- - Patient who are treated with anticoagulants are on a stable dose for at least two
weeks prior to start of radiotherapy (RT)
- The patient is male or a non-pregnant, non-lactating female.
- - Females of childbearing potential must have a negative beta-human chorionic
gonadotropin (HCG) pregnancy test within 2 weeks prior to receiving the first dose
of study medication.
Females must practice strict birth control using two different
methods (e.g. oral contraceptives in combination with barrier protection) to prevent
pregnancy for the duration of the study through 120 days after the last dose of
study medication. Males will be advised to use barrier protection starting with the
first dose of study therapy through 120 days after the last dose of study therapy)
- - The patient has a life expectancy of at least 3 months.
- - The patient has an Eastern Cooperative Oncology Group (ECOG) performance score of 0
or 1.
- - The patient shows adequate organ functions as assessed by the following laboratory
values within 2 weeks prior to first dose of study medication:
- Adequate renal function determined by serum creatinine and urea < 2 times the
upper limit of normal.
- - Adequate liver function with alanine aminotransferase (ALT), aspartate
aminotransferase (AST) and alkaline phosphatase (AP) < 3 times the upper limit
of normal, and bilirubin value < 2.5 mg/dL.
- - International normalized ratio (INR) and activated partial thromboplastin time
(aPTT) within therapeutic limits (according to the medical standard at the
institution)
- Hemoglobin > 9 g/dL.
- - Platelet count > 100 x 10^9/L.
- - White blood count (WBC) > 3 x 10^9/L.
- - Absolute neutrophil count (ANC) > 1.5 x 10^9/L.
- - Patient is able to undergo Gd MRI.
Exclusion Criteria:
- - Contraindications to the class of drugs under study, e.g. known hypersensitivity or
allergy to temozolomide (TMZ) or pembrolizumab,
- Is currently participating and receiving study therapy or has participated in a
study of an investigational agent and received study therapy or used an
investigational device within 4 weeks of the first dose of treatment.
- - Any known IDH mutation if tested.
- - Has a diagnosis of immunodeficiency.
- - Human immunodeficiency virus (HIV), hepatitis C virus (HBV) or hepatitis C virus
(HCV) infection.
- - Has a history of active tuberculosis (Bacillus Tuberculosis)
- Clinically relevant acute viral, bacterial, or fungal infection.
- - History of a second independent malignant disorder during the last three years
except non-melanoma skin cancer, in situ cervical cancer, treated superficial
bladder cancer or cured, early-stage prostate cancer in a patient with
prostate-specific antigen (PSA) level less than upper normal limit.
- - Has active autoimmune disease that has required systemic treatment in the past 2
years (i.e. with use of disease modifying agents, long-term use of corticosteroids
or immunosuppressive drugs).
Replacement therapy (eg., thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency, etc.) is not considered a form of systemic treatment.
- - Has history of, or any evidence of active, non-infectious pneumonitis.
- - Has an active infection requiring systemic therapy.
- - Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the trial, interfere with the
subject's participation for the full duration of the trial, or is not in the best
interest of the subject to participate, in the opinion of the treating investigator.
- - Has received prior therapy with an anti-programmed cell death (PD)-1, anti-PD-L1, or
anti-PD-L2 agent.
- - Prior radiotherapy to the brain or interstitial brachytherapy.
- - Prior chemotherapy for a brain tumor.
- - Intraoperative placement of carmustine wafers (Gliadel®)
- Prior therapy with immune checkpoint inhibitors or vaccination therapy against the
tumor.
- - Concurrent administration of any antitumor therapy other than TMZ/RT=>TMZ.
- - Clinically relevant psychiatric disorders/legal incapacity or a limited legal
capacity.
- - Has received a live vaccine within 30 days of planned start of study therapy.
- - Note: Seasonal influenza vaccines for injection are generally inactivated flu
vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®)
are live attenuated vaccines, and are not allowed.
- - Women who are pregnant or breast feeding,
- Intention to become pregnant during the course of the study,
- Lack of safe contraception, defined as: Female participants of childbearing
potential, not using and not willing to continue using a medically reliable method
of contraception for the entire study duration, such as oral, injectable, or
implantable contraceptives, or intrauterine contraceptive devices, or who are not
using any other method considered sufficiently reliable by the investigator in
individual cases.
- - Please note that female participants who are surgically sterilised / hysterectomised
or post-menopausal for longer than 2 years are not considered as being of child
bearing potential.
- Inability to follow the procedures of the study, e.g. due to language problems,
psychological disorders, dementia, etc. of the participant,
- Has psychiatric or substance abuse disorders including extensive use of alcohol that
would interfere with cooperation with the requirements of the trial
