A MultIceNTER Phase I Peptide VaCcine Trial for the Treatment of H3-Mutated Gliomas

Inclusion Criteria: * Patients present with histologically confirmed diagnosis of an H3.1K27M or H3.3K27M-mutated diffuse midline glioma WHO grade IV (with or without measurable residual tumor after tumor resection or biopsy after primary diagnosis) * Tumoral H3.1K27M or H3.3K27M mutation proven by immunohistochemistry or H3 DNA sequencing * No previous treatment except for surgery * Estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method) * Availability of tumor tissue for translational analyses (FFPE bulk tissue or biopsy) * Patients are scheduled to receive radiotherapy * Patients should be immunocompetent (i.e. no concomitant treatment with dexamethasone (or equivalent), or receive stable/decreasing steroid levels not exceeding 2 mg/day dexamethasone (or equivalent) during the last 3 days prior to clinical screening; no severe lymphopenia) * minimum 18 years old, smoking or non-smoking, of any ethnic origin and sex * Karnofsky Performance Status minimum 60. For patients with spinal gliomas, paralysis-caused mobility impairments will not be considered * Ability of patient to understand character and individual consequences of the clinical trial * Evidence of informed consent document personally signed and dated by the patient (or a witness in case the patient is unable to write) covering all trial-related procedures and indicating that the patient has been informed of all pertinent aspects of the study and that the patient consents to participate in the trial. * Non-nursing and non-pregnant women: Women of child-bearing potential (WOCBP) must have a negative urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) prior to the start of the investigational medicinal product (IMP). A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. In case of possible postmenopausal status or doubtful childbearing potential, assessment of serum FSH (follicle-stimulating hormone) level will be performed once at baseline visit to confirm postmenopausal status. In this case, urine pregnancy tests during the trial as well as contraception are not necessary. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. * WOCBP must be using a highly effective method of birth control (failure rate of less than 1% per year) to avoid pregnancy throughout the study and at least 5 months after the last dose of the IMP. Such methods include: * combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral intravaginal transdermal * progestogen-only hormonal contraception associated with inhibition of ovulation: oral injectable implantable * intrauterine device (IUD) * intrauterine hormone-releasing system (IUS) * bilateral tubal occlusion * vasectomised partner * sexual abstinence * Fertile men must be willing and able to use an effective method of birth control (condom) throughout the study for up to at least 5 months after the last dose of the IMP, if their sexual partners are WOCBP, using an effective method as well (acceptable methods see above). A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy. * Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures Exclusion Criteria: * Current use of immunosuppressive medication including treatment with systemic immunomodulatory agents at least 4 weeks or five half-lives of the drug, prior to starting study treatment, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication). * Previous or concurrent standard or experimental treatment for the tumor other than resection. This includes local therapies such as interstitial radiotherapy or local chemotherapy (i.e. BCNU wafers), loco-regional hyperthermia, electric fields, and antiangiogenic therapy (such as Bevacizumab). * Abnormal (≥ Grade 2 CTCAE v5.0) laboratory values for thyroid gland: free T4 and TSH * Abnormal (≥ Grade 2 CTCAE v5.0) laboratory values for hematology, liver and renal function (serum creatinine). In detail, the following values apply as exclusion criteria: 1. Hemoglobin \< 9 g/dL (5.59 mmol/L) 2. White blood cell count (WBC) decrease (\<3.0 x 109/L) or increase (\> 10.0 x 109/L) 3. Absolute neutrophil count (ANC) decrease (\< 1.5 x 109/L) 4. Platelet count decrease (\< 100 x 109/L) 5. Bilirubin \> 1.5 x ULN (upper limit of normal according to the performing lab´s reference range) 6. ALT \> 2.5 x ULN 7. AST \> 2.5 x ULN 8. GGT \> 2.5 x ULN 9. Serum creatinine increase (\> 1.5 x ULN) * Patients with history or presence of HIV and/or HBV/HCV positivity (testing performed according to local standards) * Patients with history or known presence of tuberculosis (positive QuantiFERON®-TB Gold test or tuberculin skin test). Patients with an indeterminate result of the QuantiFERON®-TB Gold test are not eligible unless additional testing demonstrates a negative result (tuberculin skin test or repeated QuantiFERON®-TB Gold test). If a tuberculin skin test is performed, an induration of \> 6 mm is "positive" for a patient with history of BCG vaccine, while an induration of \> 10 mm is "positive" for a patient without history of BCG vaccine. If necessary, a QuantiFERON®-TB Gold test might be complemented by additional specific diagnostic tests as per standard procedures. * Patients with severe infection(s) or signs/symptoms of infection within 2 weeks prior to start of treatment including radiotherapy and IMP * Active infection requiring systemic therapy * Patients who have received a live, attenuated vaccine within 4 weeks prior to start of treatment including radiotherapy and IMP * Patients with a prior solid organ transplantation or hematopoietic stem cell transplantation * Active autoimmune disease including history of severe autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible * Clinically significant (i.e. active) cardiovascular disease: Cerebral vascular accident/stroke (\< 6 months prior to enrolment), myocardial infarction (\< 6 months prior to enrolment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication * History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within the last 5 years unless the patient has been diseasefree for 5 years. * Other severe acute or chronic medical conditions including colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study * History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v5.0 Grade ≥ 3) * Participation in other clinical trials or their observation period during the last 30 days before start of treatment including radiotherapy and IMP No patient will be allowed to enroll in this trial more than once.