Multi Peptide Vaccination with XS15 in Addition to Standard Postoperative Radiation Therapy and Temozolomide Chemotherapy in Newly Diagnosed Glioblastoma

NCT04842513 | Completed Phase 1 DMC

• 1 other identifier: 2020-003357-30
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Newly diagnosed HLA-A2-positive MGMT-methylated glioblastoma patients will be vaccinated with a Multi peptide vaccination with Pam3Cys-GDPKHPKSF (XS15) as an immunomodulator in addition to standard postoperative radiation therapy and temozolomide chemotherapy to assess immunogenicity, efficacy, safety of the combination of multipeptide vaccination and the immune modulator XS15 emulsified in Montanide ISA 51 VG

Conditions

Glioblastoma Multiforme of Brain

Outcome Measures

Primary Outcomes (2)

• Adevrse Events

  The assessment of safety of the IMP will be accomplished by documentation of adverse events and grading according to CTCAE from first vaccination throughout the end of treatment, until 30 days after last vaccination.

  at 12 months after last vaccination

• Change of immunogenicity parameter from baselien

  The assessment of immunogenicity is the central biological efficacy endpoint of the clinical trial. Measurements of the induction of T-cell response after vaccination at 30 days, 60 days and 90 days from first vaccination and at 12 months after last vaccinationcompared to baseline as determined by ELISpot

  at 30 days, 60 days and 90 days from first vaccination and at 12 months after last vaccination

Study Arms (1)

Multipeptide plus XS15

EXPERIMENTAL

The vaccine will be applied by subcutaneous injection into the abdominal skin of the study patient. Vaccination will take place monthly (V1, V2 and V3). A total of three vaccinations will be performed. Peptide vaccines should be injected into the skin at the lower part of the abdomen of the patients. The exact site of vaccination (right or left) will be determined at the time of first vaccination and should not be changed during subsequent vaccinations.

Drug: Multipeptide plus XS15

Interventions

Multipeptide plus XS15 DRUG

The vaccine will be applied by subcutaneous injection into the abdominal skin of the study patient. Vaccination will take place monthly (V1, V2 and V3). A total of three vaccinations will be performed. Peptide vaccines should be injected into the skin at the lower part of the abdomen of the patients. The exact site of vaccination (right or left) will be determined at the time of first vaccination and should not be changed during subsequent vaccinations.

Multipeptide plus XS15

Eligibility Criteria

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

You may qualify if:

• Subjects meeting all of the following criteria will be considered for admission to the trial:
• For screening phase: (Consent C1)
• \. .Must be ≥ 18 years at the time of signing the informed consent 2. Suspected Glioblastoma (presenting with a MRI suggestive of glioblastoma and eligible for gross or subtotal resection and standard radiotherapy with temozolomide) For Vaccination phase (Consent C2)
• Histologically confirmed, newly diagnosed IDH1-wildtype glioblastoma (astrocytoma WHO grade IV)
• MGMT gene promoter methylation
• HLA phenotype HLA-A\*02:01 (as determined by a PCR-based 4-digit typing method)
• Gross or subtotal resection (20%, as determined by MRI)
• Postoperative MRI
• KPS ≥70%
• Life expectancy \> 6 months
• Patient is a candidate for and willing to receive standard radiation therapy with TMZ followed by maintenance TMZ cycles
• Patient is not on steroids or on stable or decreasing steroid levels not exceeding 2 mg/day dexamethasone (or equivalent doses of other steroids) during the last 3 days prior to first dose of IMP (Vaccination 1)
• Absolute lymphocyte count (ALC) \>0.5 x109/L (re-screening of lymphocyte counts is allowed at day of vaccination)
• Ability of subject to understand and the willingness to sign written informed consent for study participation prior to any study related assessments/procedures. Able to adhere to the study visit schedule and other protocol requirements.
• Female Patient of childbearing potential1 and male patients with female partner of childbearing potential1 is willing to use highly effective contraceptive methods during treatment and for 30 days after the end of treatment. According to the CTFG Recommendations highly effective contraceptive methods are:

You may not qualify if:

• Subjects presenting with any of the following criteria will not be included in the trial:
• Karnofsky performance score (KPS) \< 70%
• Patient who cannot undergo MRI assessments
• Only Biopsy available
• Women during pregnancy and lactation.
• 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.
• Participation in other clinical trials or observation period of competing trials.
• Platelet count decrease \< 75 x109/L
• Bilirubin \> 1.5 x ULN (upper limit of normal according to the performing lab's reference range)
• ALT4 \> 3 x ULN
• AST5 \> 3 x ULN
• GGT \> 2.5 x ULN
• Serum creatinine increased \> 1.5 x ULN
• HIV infection or active Hepatitis B or C infection, or active infections requiring oral or intravenous antibiotics or that can cause a severe disease and pose a severe danger to lab personnel working on patients' blood or tissue (e.g. rabies).
• Clinically relevant autoimmune diseases (with the exception of thyroid diseases).

Sponsors & Collaborators

• University Hospital Tuebingen: lead

Study Sites (1)

University Hospital Tübingen

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Study Officials

• Ghazaleh Tabatabai, Prof

  University Hospital Tuebingen

  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 1, 2021
• First Posted: April 13, 2021
• Study Start: May 3, 2021
• Primary Completion: July 31, 2024
• Study Completion: July 31, 2024
• Last Updated: January 10, 2025

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)