VXM01 Plus Avelumab Combination Study in Progressive Glioblastoma

NCT03750071 | Unknown Phase 1 DMC

• 1 other identifier: VXM01-AVE-04-INT
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

VXM01 in combination with avelumab in n=30 patients with progressive glioblastoma following standard treatment, with or without second surgery

Conditions

Recurrent Glioblastoma

Outcome Measures

Primary Outcomes (1)

• Treatment-emerging adverse events (safety and tolerability of VXM01 in combination with avelumab)

  AEs listed together with information on onset, duration, severity, seriousness, relationship to the study drug, relationship to chemotherapy and to the underlying disease, outcome, and action taken. Frequency tables by System Organ Class and preferred term.

  Up to 60 weeks after first IMP administration

Secondary Outcomes (6)

• Clinical response as assessed by time to progression (TTP)

  Up to 60 weeks after first IMP administration

• Clinical response as assessed by progression free survival (PFS)

  Up to 60 weeks after first IMP administration

• Clinical response as assessed by recurrence-free survival after re-operation (RFS)

  Up to 60 weeks after first IMP administration

• Clinical response as assessed by Overall Survival (OS)

  Up to 60 weeks after first IMP administration

• Best overall response (OR) on MRI according to iRANO in subjects with or without surgery prior to trial entry (up to re-operation)

  Up to 60 weeks after first IMP administration

Study Arms (1)

VXM01/Avelumab

EXPERIMENTAL

Combination of VXM01, Ty21a transformed with a eukaryotic expression cassette encoding VEGFR-2, and anti-PD-L1 Checkpoint Inhibitor Avelumab

Biological: VXM01; Biological: Avelumab

Interventions

VXM01 BIOLOGICAL

Ty21a transformed with a eukaryotic VEGFR-2 Expression Plasmid

Also known as: Investigational VEGFR-2 DNA Vaccine

VXM01/Avelumab

Avelumab BIOLOGICAL

Monoclonal anti-PD-L1 Antibody

Also known as: Bavencio

VXM01/Avelumab

Eligibility Criteria

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

You may qualify if:

• Subjects who are able to understand and follow instructions during the trial
• Ability and willingness to give written informed consent, signed and dated
• Male or female subjects. Female subjects must be post-menopausal for at least 2 years or surgically sterile
• Age ≥18 years
• Histologically diagnosed intracranial supratentorial malignant glioma (glioblastoma WHO Grade IV)
• 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
• Candidates for a tumor reoperation (for the resectable arm \[n=6\] only)
• \- Neurosurgical intervention should be postponable for 30 days
• 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 \<1.5x ULN. Subjects with documented benign cyclical neutropenia are allowed if WBC count is ≥ 1.5 × 109/L with absolute neutrophil count ≥ 1.0 × 109/L and appropriate hematology parameters: leukocytes ≥4.0 x 109 / L, lymphocytes ≥0.6 x 109/L
• Adequate hepatic function defined by a total bilirubin level ≤ 1.5 × the upper limit of normal range (ULN), an aspartate aminotransferase (AST), level ≤ 2.5 × ULN, and an alanine aminotransferase (ALT) level ≤ 2.5 × ULN or, for subjects with documented metastatic disease to the liver, AST and ALT levels ≤ 5 × ULN. Subjects with documented Gilbert disease are allowed if total bilirubin ≤ 3 x ULN
• Adequate renal function defined by an estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula
• Patients must be able to undergo MRI
• Absence of active bacterial infection requiring antibiotic treatment
• Karnofsky performance status ≥70
• Primary tumor samples available for pathology review, central detection of T-cell responses in the peripheral blood and in the tumor tissue

You may not qualify if:

• Cardiovascular disease defined as:
• Uncontrolled hypertension (systolic blood pressure \>160 mmHg or diastolic blood pressure \>100 mmHg)
• Arterial thromboembolic event within 6 months before trial entry, including:
• i. Myocardial infarction ii. Unstable angina pectoris iii. Cerebrovascular accident iv. Transient ischemic attack
• Congestive heart failure New York Heart Association grade III to IV
• Serious ventricular arrhythmia requiring medication and arrhythmias requiring Implantable Cardioverter Defibrillator (ICDs)
• Clinically significant peripheral artery disease \> grade 2b according to Fontaine
• History of intracranial hemorrhage
• Hemoptysis within 6 months before trial entry
• Known oesophageal varices
• Significant traumatic injury or surgery within 4 weeks before trial entry
• Gastrointestinal fistula
• Thrombolysis therapy within 4 weeks before trial entry
• History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that based on the investigator's 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
• Previous malignant disease (other than the tumor disease for this trial) within the last 5 years (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

Sponsors & Collaborators

• Vaximm GmbH: lead
• Merck KGaA, Darmstadt, Germany: collaborator
• Pfizer: collaborator

Study Sites (2)

Neurology Clinic and National Center for Tumor Diseases

Heidelberg, 69120, Germany

Location

Neurology Clinic

Mannheim, 68167, Germany

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

avelumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Wolfgang Wick, MD

  University Clinics Heidelberg

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 26, 2018
• First Posted: November 21, 2018
• Study Start: November 21, 2018
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2022
• Last Updated: October 20, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2)