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Pembrolizumab in Association With the IMA950/Poly-ICLC for Relapsing Glioblastoma (IMA950-106)

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ClinicalTrials.gov Identifier: NCT03665545
Recruitment Status : Recruiting
First Posted : September 11, 2018
Last Update Posted : June 17, 2019
Sponsor:
Information provided by (Responsible Party):
Pierre-Yves Dietrich, University Hospital, Geneva

Brief Summary:

Monocentric randomized phase I/II trial, including 24 patients diagnosed with relapsing glioblastoma (GBM) irrespective of MGMT and IDH gene status.

Following diagnosis of relapsing glioblastoma by either brain CT scan or MRI, patients will be randomized in 2 arms:

  1. Arm 1: IMA950 mixed with Poly-ICLC administered subcutaneously
  2. Arm 2: Pembrolizumab 200mg q3w IV and IMA950 mixed with Poly-ICLC administered subcutaneously

The first phase of treatment will last 6 weeks, then surgery will be performed (done if clinically possible ad indicated). In case of available brain tissue, extensive analysis of the tumor immune response will be performed. Assessment of systemic immune response by PBMC immunomonitoring will be systematically done before and after surgery.


Condition or disease Intervention/treatment Phase
Glioblastoma Multiforme Glioblastoma, Adult Glioma of Brain Glioblastoma Multiforme of Brain Drug: IMA950/Poly-ICLC Drug: IMA950/Poly-ICLC and pembrolizumab Phase 1 Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pembrolizumab in Association With the Multipeptide Vaccine IMA950 Adjuvanted With Poly-ICLC for Relapsing Glioblastoma: a Randomized Phase I/ II Trial
Actual Study Start Date : October 25, 2018
Estimated Primary Completion Date : October 30, 2021
Estimated Study Completion Date : November 10, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: IMA950/Poly-ICLC
IMA950 mixed with Poly-ICLC administered subcutaneously
Drug: IMA950/Poly-ICLC
IMA950 mixed with Poly-ICLC administered subcutaneously

Experimental: IMA950/Poly-ICLC and pembrolizumab
Pembrolizumab 200mg q3w IV and IMA950 mixed with Poly- ICLC administered subcutaneously
Drug: IMA950/Poly-ICLC
IMA950 mixed with Poly-ICLC administered subcutaneously

Drug: IMA950/Poly-ICLC and pembrolizumab
IMA950 mixed with Poly-ICLC administered subcutaneously in combination with pembrolizumab




Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events [ Time Frame: From the time of treatment randomization through 30 days following cessation of treatment ]
    To assess tolerability and safety of IMA950 adjuvanted with Poly-ICLC when given together with pembrolizumab, using CTCAE v.4.03


Secondary Outcome Measures :
  1. Progression-free survival at 6, 9, 12 months [ Time Frame: through study completion, an average of 3 years ]
    To estimate 6, 9 and 12-month progression-free survival (PFS) using gadolinium-enhanced MRI and clinical assessment according to revised iRANO criteria

  2. Overall Survival [ Time Frame: through study completion, an average of 3 years ]
    To estimate OS, defined as the time between the date of study entry and the date of death due to any cause. Subjects who have not died at the time of last known follow-up will be censored

  3. Patient-reported Quality of life [ Time Frame: through study completion, an average of 3 years ]
    Quality of life patient-reported outcomes (EORTC QLQ-C30 questionnaire)


Other Outcome Measures:
  1. Tumor Infiltrating Lymphocyte (TIL) density [ Time Frame: through study completion, an average of 3 years ]
    To assess synergy/immunogenicity of IMA950 plus Poly-ICLC when given together with Pembrolizumab using Tumor Infiltrating Lymphocyte (TIL) density assessment

  2. Vaccine-specific CD4 and CD8 cells [ Time Frame: through study completion, an average of 3 years ]
    To assess synergy/immunogenicity of IMA950 plus Poly-ICLC when given together with Pembrolizumab by assessing vaccine-induced peripheral immune responses by flow cytometry or IHC as surrogate markers



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  1. Histological documentation of glioblastoma (de novo or secondary GBM).
  2. Patient must be at first or subsequent relapse.
  3. HLA-A*0201 positive patients (after pre-screening).
  4. ECOG performance status of 0 or 1.
  5. Age > 18 years, life expectancy of least 4 months.
  6. Patient must be on stable or decreasing dose of steroids, with a maximal dose of Dexamethasone of 4mg/day or equivalent.
  7. Adequate bone marrow, liver and kidney function (see Table 2 for definition).
  8. Negative Hepatitis B serology (HBcAg-seronegative).
  9. Capable of co-operating with the protocol schedule of Pembrolizumab combined with IMA950 and Poly-ICLC and follow-up.
  10. Have measurable disease according to the iRANO criteria. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
  11. Be willing and able to provide written informed consent for the trial.
  12. Be willing to provide tissue from a study-specific biopsy of a tumor lesion.
  13. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. A urine test can be considered if the serum test is not available.
  14. Female subjects of childbearing potential (Section 5.6.2) must be willing to use 2 methods of contraception or be surgically sterile, or abstain from heterosexual activity as outlined in Section 5.6.2 - Contraception, for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been in menopause for more than one year.

    Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

  15. Male subjects of childbearing potential must agree to use an adequate method of contraception as outlined in Section 5.6.2- Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.

Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

5.1.4. Main Study Exclusion Criteria

The subject must be excluded from participating in the trial if the subject:

  1. Any other vaccination given within 2 weeks before first IMA950 vaccination.
  2. Diagnosis of immunodeficiency or active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a condition that requires systemic steroids (> 10mg/day prednisone or equivalent) or immunosuppressive agents. Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  3. Patients with evidence of history bleeding diathesis.
  4. Pregnant or breastfeeding patients, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
  5. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  6. 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.
  7. Has a known history of active TB (Bacillus Tuberculosis)
  8. Hypersensitivity to pembrolizumab or any of its excipients.
  9. Has had a prior anti-cancer monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  10. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.

    Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.

    Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.

  11. Has known history of, or any evidence of active (non-infectious) pneumonitis that required(s) steroids.
  12. Has an active infection requiring systemic therapy.
  13. 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.
  14. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  15. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
  16. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  17. Has known past or active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected). Only patients with negative serology for past or current exposure to HBV and HCV will be eligible.
  18. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03665545


Contacts
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Contact: Aurélie VUILLEUMIER, Dr +41795535100 Aurelie.Vuilleumier@hcuge.ch
Contact: Pierre-Yves DIETRICH, Prof +41223729861 Pierre-Yves.Dietrich@hcuge.ch

Locations
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Switzerland
University Hospitals of Geneva Recruiting
Geneva, Switzerland, 1211
Contact: Cristina Riccadonna, PhD    +41(0)223722910    Cristina.Riccadonna@hcuge.ch   
Sponsors and Collaborators
University Hospital, Geneva
Investigators
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Principal Investigator: Pierre-Yves Dietrich, Prof. University Hospital, Geneva
Study Director: Pierre-Yves Dietrich, Prof. University Hospital, Geneva

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Responsible Party: Pierre-Yves Dietrich, Principal Investigator, University Hospital, Geneva
ClinicalTrials.gov Identifier: NCT03665545     History of Changes
Other Study ID Numbers: IMA950-106/CER 2018-00718
MK3475-480 ( Other Identifier: MSD )
First Posted: September 11, 2018    Key Record Dates
Last Update Posted: June 17, 2019
Last Verified: June 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Pierre-Yves Dietrich, University Hospital, Geneva:
glioblastoma

Additional relevant MeSH terms:
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Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Pembrolizumab
Poly ICLC
Poly I-C
Carboxymethylcellulose Sodium
Antineoplastic Agents, Immunological
Antineoplastic Agents
Interferon Inducers
Immunologic Factors
Physiological Effects of Drugs
Laxatives
Gastrointestinal Agents
Antiviral Agents
Anti-Infective Agents