Progressive glioblastoma (WHO grade IV) MedDRA version: 20.0 Level: PT Classification code 10018336 Term: Glioblastoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: VXM01
Product Code: VXM01
Pharmaceutical Form: Oral suspension
INN or Proposed INN: not yet assigned
Current Sponsor code: VXM01
Other descriptive name: VXM01
Concentration unit: CFU/ml
Sponsors
VAXIMM GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects who are able to understand and follow instructions during the trial 2. Ability and willingness to give written informed consent, signed and dated 3. Male or female subjects. Female subjects must be post-menopausal for at least 2 years or surgically sterile 4. Age =18 years 5. Histologically diagnosed intracranial supratentorial malignant glioma (contrast-enhancing glioblastoma WHO Grade IV) 6. Evidence of tumor progression by RANO criteria following at least one prior therapy regimen that must have contained radiation and chemotherapy with temozolomide, as measured by MRI ? Raditotherapy must have been completed at least 3 months prior to the inclusion visit 7. Candidates for a tumor reoperation (for the resectable arm [n=6] only) ? Neurosurgical intervention should be postponable for 30 days 8. Adequate bone marrow function including: Absolute neutrophil count (ANC) =1,500/mm3 or =1.5 x 109/L; Platelets = 100,000/mm3 or =100 x 109/L; Hemoglobin = 9 g/dL (may have been transfused); INR =65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: 1. Cardiovascular disease: - uncontrolled hypertension - arterial thromboembolic event within 6 m before trial entry 2. Congestive heart failure NY Heart Association grade III to IV 3. Serious ventricular arrhythmia requiring medication and arrhythmias requiring ICD 4. Clinically significant peripheral artery disease > grade 2b according to Fontaine 5. History of relevant intracranial hemorrhage 6. Hemoptysis within 6 m before trial entry 7. Known oesophageal varices 8. Upper or lower gastrointestinal bleeding within 6 m before inclusion 9. Significant traumatic injury or surgery within 4 w before trial entry 10. Non-healing wound, incomplete wound healing, bone fracture or gastrointestinal ulcers within three years before inclusion, or positive gastroscopy within 3 m before inclusion 11. Gastrointestinal fistula 12. Thrombolysis therapy within 4 w before trial entry 13. History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that based on the investigators judgement provides a reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the trial results or render the patient at high risk for treatment complications 14. Previous malignant disease (other than glioblastoma) within the last 5 y (except adequately treated non-melanoma skin cancers, carcinoma in situ of skin, bladder, cervix, colon/rectum, breast, or prostate) unless a complete remission without further recurrence was achieved at least 2 years prior to trial entry and the subject was deemed to have been cured with no additional therapy required or anticipated to be required 15. Prior organ transplantation, including allogeneic stem cell transplantation 16. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent: a. Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible b. Administration of steroids through a route known to result in a minimal systemic exposure are acceptable 17. History of uncontrolled intercurrent illness including but not limited to uncontrolled diabetes 18. Known prior hypersensitivity to investigational product or any component in its formulations or any other drug scheduled or likely to be given during the trial, including known severe hypersensitivity to monoclonal antibodies (Grade = 3) 19. Persisting toxicity related to prior therapy (Grade > 1); however, alopecia, sensory neuropathy Grade = 2, or other Grade = 2 AEs not constituting a safety risk based on investigator’s judgment are acceptable 20. Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune 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 trial participation or trial treatment administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the patient inappropriate for entry into this trial 21. Active infection requiring systemic therapy 22. Known history of HIV or known acquired immunodeficiency syndrome or multi-drug resistant gram-negative bacteria 23. HBV or HCV infection at screening 24. Women of childbearing potential 25. History of serious ophthalmologic
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To examine the safety and tolerability of VXM01 in combination with avelumab;Secondary Objective: Secondary objectives •Efficacy of VXM01 in combination with avelumab by assessment of tumor objective response rate (ORR) per Immunotherapy Response Assessment in Neuro-Oncology (iRANO) criteria and according to Okada et al., 2015 in non-resected and resected subjects (up to re-operation) •Efficacy of VXM01 in combination with avelumab by assessment of clinical response Exploratory objectives •Effect of VXM01 plus avelumab on immuno- and biomarkers in tumor tissue and blood samples pre-and post-treatment •To characterize the pharmacokinetics (PK) of avelumab in combination with VXM01 •To characterize the immunogenicity of avelumab in combination with VXM01 • To characterize the gut microbiome pre- and post treatment;Primary end point(s): Safety and tolerability up to 60 weeks after first IMP administration (incl. EoS visit, week 60);Timepoint(s) of evaluation of this end point: Every study visit up to and including EoS visit, week 60 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints • Best overall response (OR) and Duration of Response (DoR) on MRI according to iRANO in subjects with or without surgery prior to trial entry (up to re-operation) • Clinical response as assessed by time to progression (TTP), progression free survival (PFS), recurrence-free survival after re-operation (RFS) and overall survival (OS) up to end of trial Exploratory endpoints • Patient-individual VEGFR-2 specific IFN-gamma T cell responses pre- and post-vaccination, determined by Enzyme Linked Immuno Spot (ELISpot) using cryopreserved peripheral blood mononuclear cells (all subjects) • Frequency of peripheral regulatory T cells (Tregs) and myeloid derived suppressor cells (MDSCs) measured using flow cytometry analysis • Tumor tissue immunohistochemistry / -fluorescence staining evaluations including, but not limited to, VEGFR-2 expression on tumor cells and tumor vasculature, effector T cell infiltration, Tregs, MDSCs, PD-1, PD-L1 (primary tumors of all subjects and recurrent tumors of re-operated subjects) • Tumor PTEN mutation/deletion status (primary tumors of all subjects and recurrent tumors of re-operated subjects) • Microsatellite instability (MSI) / DNA mismatch repair (MMR) status • TCR sequencing of tumor infiltrating lymphocytes (TILs) and peripheral T cells. • PK profile of avelumab in combination with VXM01 • Anti-avelumab anti-drug antibodies (ADA) • Gut microbiome status;Timepoint(s) of evaluation of this end point: End of study | — |
Countries
Germany, Netherlands
Contacts
Public ContactSubmission Specialist
SMS-oncology (CATO SMS)
Outcome results
None listed