Mittwoch, 27. Januar 2021
Navigation öffnen


PERGOLA Pembrolizumab for Newly Diagnosed Glioblastoma



Oktober 2020

Letztes Update:


Indikation (Clinical Trials):


Erwachsene (18+)

Phase 2

University of Zurich

Merck Sharp & Dohme Corp.


Patrick Roth, MD
Principal Investigator
University of Zurich


Studienlocations (3 von 3)


Brief Summary:

The study explores the addition of pembrolizumab to temozolomide-based radiotherapy in

patients with newly diagnosed glioblastoma.


Inclusion Criteria:

- The patient has provided written informed consent prior to any study-related


- 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


- 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


- 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


- 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)


- 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


- 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


Primary outcome:

1. Overall survival at 12 months (Time Frame - At 12 months):
To explore whether the addition of pembrolizumab to standard temozolomide-based radiochemotherapy improves the outcome of newly diagnosed glioblastoma or gliosarcoma patients, determined by the overall survival rate at 12 months

Secondary outcome:

1. Response rates using (i)RANO (immunotherapy response assessment in neuro-oncology) criteria (Time Frame - From the inclusion in the study until the end of follow-up (up to approximately 36 months))

2. Progression-free survival (PFS) at 6 and 12 months (Time Frame - At 6 and 12 months)

3. Time to treatment failure (TTF) (Time Frame - From the inclusion in the study until the end of follow-up (up to approximately 36 months))

4. Health-related Quality of life (HRQol) (Time Frame - From the inclusion in the study until the end of follow-up (up to approximately 36 months)):
HRQoL will be assessed with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) version 3. Scoring: 0 to 100. Higher scores mean a better level of functioning.

5. Correlation of programmed cell death (PD-1) ligand 1 (PD-L1) expression levels with response to treatment and outcome (Time Frame - From the inclusion in the study until the end of follow-up (up to approximately 36 months)):
Expression levels of PD-L1 will be determined in the tumor tissue and correlated with response as determined by MRI and progression-free as well as overall survival

Geprüfte Regime

  • Pembrolizumab:
    Pembrolizumab will be added to standard of care


ASH 2020
  • Phase-III-Studie ASCEMBL bei resistenten/intoleranten Patienten mit CML: STAMP-Inhibitor Asciminib deutlich effektiver als TKI Bosutinib
  • Ruxolitinib-resistente/-intolerante MF-Patienten profitieren im klinischen Alltag möglicherweise von einer Rechallenge
  • Real-world-Daten zu PV: Rechtzeitige Umstellung von HU auf Ruxolitinib wirkt möglicherweise Anstieg thromboembolischer Ereignisse entgegen
  • 5-Jahres-Daten der RESPONSE-2-Studie: Überlegenheit von Ruxolitinib gegenüber BAT im Langzeitverlauf bestätigt
  • Phase-I-Studie: Anhaltendes molekulares Ansprechen mit neuem BCR-ABL-Inhibitor Asciminib bei CML-Patienten mit T315I-Resistenzmutation
  • Patienten mit ITP sind emotional erheblich belastet
  • r/r DLBCL: Vielversprechende erste Daten zur CAR-T-Zell-Therapie mit Tisagenlecleucel in Kombination mit Ibrutinib
  • r/r FL: CAR-T-Zell-Therapie mit Tisagenlecleucel wirksam und sicher
  • Myelofibrose: Ruxolitinib-Startdosis von 10 mg 2x tägl. auch bei initial niedriger Thrombozytenzahl sicher anwendbar
  • Phase-III-Studie REACH3: Ruxolitinib bei chronischer steroidrefraktärer oder steroidabhängiger GvHD wirksamer als die beste verfügbare Therapie