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

NCT04808245 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: NCT-2018-576
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 8

Brief Summary

The study "A MultIceNTER Phase I Peptide VaCcine Trial to Exploit NeoePitope-Specific T Cells for the Treatment of H3K27M-Mutated Gliomas - (INTERCEPT H3)" is a non-controlled, open-label, single arm, multicenter phase I trial involving patients with gliomas carrying an H3.1K27M or H3.3K27M mutation.

Conditions

Newly Diagnosed H3-mutated Glioma

Keywords

Diffuse midline glioma; Histone H3; H3K27M; DIPG; Glioma; Glioblastoma; Immunotherapy

Outcome Measures

Primary Outcomes (2)

• Assessment of safety of repeated fixed dose vaccinations with the H3K27M peptide vaccine administered with radiotherapy and Atezolizumab in patients with H3K27M-mutant gliomas. Primary safety endpoint is the Regime Limiting Toxicity (RLT).

  Safety of H3K27M peptide vaccine administered with radiotherapy and Atezolizumab. Primary safety endpoint is the Regime Limiting Toxicity (RLT).

  Through study completion, an average of one year

• Assessment of immunogenicity of repeated fixed dose vaccinations with the H3K27M peptide vaccine administered with radiotherapy and Atezolizumab in patients with H3K27M-mutant gliomas.

  Immunogenicity (Immune response Yes/No) will be assessed for all evaluable patients. The primary immunogenicity endpoint is the presence of an H3K27M-specific T-cell response. H3K27M-specific T cell responses are measured on Peripheral Blood Mononuclear Cells (PBMC) using IFN-gamma ELISpot.

  From Day 1 until the date of study termination (until day 540); approximately 16 times

Secondary Outcomes (4)

• Progression-free survival (PFS)

  From day of first diagnosis until the date of first documented progression or date of death from any cause, whichever came first, assessed up to the date of study termination (approximately until day 540)

• Overall response rate (ORR)

  Baseline visit to end of study (approximately until day 540)

• Analyze the association between immunogenicity and the clinical outcome parameters ORR

  Through study completion, an average of one year

• Analyze the association between immunogenicity and the clinical outcome parameters PFS

  Through study completion, an average of one year

Study Arms (1)

Standard patient cohort

EXPERIMENTAL

All fifteen patients will receive in total 11 doses of H3K27M peptide vaccine starting with standard radiotherapy (RT) and 14 doses of the human anti-PD-L1 antibody Atezolizumab/ Tecentriq® (every three weeks, q3w) starting four weeks after completion of RT. The first 3 vaccines will be given bi-weekly (q2w) in combination with RT. One dose of vaccination will be given at the beginning of recovery (RE) period following RT. Vaccines 5-11 (q6w) will be initiated with Atezolizumab after completion of RE. The H3K27M peptide vaccine is administered in combination with topical Imiquimod that serves as an adjuvant. For safety reasons, the first three patients will be enrolled sequentially: Each patient will receive the first vaccination at the earliest 28 days after the previous patient has received the first vaccination.

Drug: Tecentriq 1200 MG in 20 ML Injection; Biological: H3K27M peptide vaccine; Other: Imiquimod (5%)

Interventions

Tecentriq 1200 MG in 20 ML Injection DRUG

One vial of Tecentriq® (1200 mg) will be administered as an intravenous (i.v.) infusion over 60 minutes every 3 weeks starting 4 weeks after radiotherapy. If the first infusion is tolerated, all subsequent infusions will be delivered over 30 minutes.

Also known as: Atezolizumab

Standard patient cohort

H3K27M peptide vaccine BIOLOGICAL

The H3K27M peptide vaccine is injected subcutaneously (s.c.). For a single vaccination 300 μg of the peptide will be emulsified in a total volume of 1 ml.

Standard patient cohort

Imiquimod (5%) OTHER

One sachet of Aldara® cream (250 mg) will be applied to an area of 5 x 5 cm around the injection site of the H3K27M peptide vaccine 15 min after vaccination and left on the skin for approximately 8 hours according to the instructions in the SmPC. 24 hours after the vaccination a second sachet of Aldara® will be applied by the patient as instructed above and left on the skin for approximately 8 hours.

Also known as: Aldara

Standard patient cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Hemoglobin \< 9 g/dL (5.59 mmol/L)
• White blood cell count (WBC) decrease (\<3.0 x 109/L) or increase (\> 10.0 x 109/L)
• Absolute neutrophil count (ANC) decrease (\< 1.5 x 109/L)
• Platelet count decrease (\< 100 x 109/L)
• Bilirubin \> 1.5 x ULN (upper limit of normal according to the performing lab´s reference range)
• ALT \> 2.5 x ULN
• AST \> 2.5 x ULN
• GGT \> 2.5 x ULN
• 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

Sponsors & Collaborators

• German Cancer Research Center: lead
• Johannes Gutenberg University Mainz: collaborator
• Charite University, Berlin, Germany: collaborator
• Roche Pharma AG: collaborator
• German Cancer Aid: collaborator

Study Sites (8)

Department of Neurology and Polyclinic, Universitiy Clinic Heidelberg

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

University Medical Center Mannheim, Department of Neurology

Mannheim, Baden-Wurttemberg, 68167, Germany

Location

University Clinic Tuebingen, Neurological Clinic, Department of Neurology

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Dr. Senckenberg Institute for Neurooncology, University Hospital Frankfurt

Frankfurt am Main, Hesse, 60528, Germany

Location

Clinical Neuro-Oncology Section, University Hospital Bonn (UKB)

Bonn, North Rhine-Westphalia, 53127, Germany

Location

Neurooncology Department, University Hospital Essen

Essen, North Rhine-Westphalia, 45147, Germany

Location

Clinic and Polyclinic for Neurosurgery, University Hospital Carl Gustav Carus Dresden

Dresden, Saxony, 1307, Germany

Location

Department of Neurosurgery with Pediatric Neurosurgery

Berlin, State of Berlin, 10117, Germany

Location

Related Publications (2)

• Ochs K, Ott M, Bunse T, Sahm F, Bunse L, Deumelandt K, Sonner JK, Keil M, von Deimling A, Wick W, Platten M. K27M-mutant histone-3 as a novel target for glioma immunotherapy. Oncoimmunology. 2017 May 12;6(7):e1328340. doi: 10.1080/2162402X.2017.1328340. eCollection 2017.

  PMID: 28811969 BACKGROUND

• Grassl N, Sahm K, Susse H, Poschke I, Bunse L, Bunse T, Boschert T, Mildenberger I, Rupp AK, Ewinger MP, Lanz LM, Denk M, Tabatabai G, Ronellenfitsch MW, Herrlinger U, Glas M, Krex D, Vajkoczy P, Wick A, Harting I, Sahm F, von Deimling A, Bendszus M, Wick W, Platten M. INTERCEPT H3: a multicenter phase I peptide vaccine trial for the treatment of H3-mutated diffuse midline gliomas. Neurol Res Pract. 2023 Oct 19;5(1):55. doi: 10.1186/s42466-023-00282-4.

  PMID: 37853454 DERIVED

MeSH Terms

Conditions

Glioma; Glioblastoma

Interventions

atezolizumab; Injections; Imiquimod

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Astrocytoma

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Michael Platten, Prof.

  German Cancer Research Center Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2021
• First Posted: March 22, 2021
• Study Start: February 15, 2023
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: September 22, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (8)