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

Criteria the registry did not label

• Histological documentation of glioblastoma (de novo or secondary GBM).
• Patient must be at first or subsequent relapse.
• HLA-A\*0201 positive patients (after pre-screening).
• ECOG performance status of 0 or 1.
• Age \> 18 years, life expectancy of least 4 months.
• Patient must be on stable or decreasing dose of steroids administered for glioblastoma, with a maximal dose of Dexamethasone of 4mg/day or equivalent.
• Adequate bone marrow, liver and kidney function (see Table 2 for definition).
• Negative Hepatitis B serology (HBcAg-seronegative).
• Capable of co-operating with the protocol schedule of Pembrolizumab combined with IMA950 and Poly-ICLC and follow-up.
• 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.
• Be willing and able to provide written informed consent for the trial.
• Be willing to provide tissue from a study-specific biopsy of a tumor lesion.
• 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.
• 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.
• 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:
• Any other vaccination given within 2 weeks before first IMA950 vaccination.
• 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 other than glioblastoma 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.
• Patients with evidence of history bleeding diathesis.
• 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.
• 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.
• 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.
• Has a known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients.
• 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.
• 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.
• Has known history of, or any evidence of active (non-infectious) pneumonitis that required(s) steroids.
• 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 known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
• Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• 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.
• 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.