GAPVAC Phase I Trial in Newly Diagnosed Glioblastoma Patients

NCT02149225 | Completed Phase 1 DMC

• 2 other identifiers: GAPVAC-1012013-002801-71
• Study Type: interventional
• Target: 16
• Locations: 5 countries
• Sites: 6

Brief Summary

The primary objective of this study is to assess the safety and tolerability, feasibility and biological activity (immunogenicity) of the actively personalized vaccination (APVAC) concept in newly diagnosed glioblastoma (GB) patients.

Conditions

Glioblastoma

Keywords

Actively personalized peptide vaccinations; Newly diagnosed Glioblastoma; Concurrent to first line temozolomide maintenance therapy

Outcome Measures

Primary Outcomes (2)

• Safety profile of patient-tailored APVAC vaccines when administered with immunomodulators concurrent to maintenance TMZ cycles

  Number of Adverse Events (AEs) and Serious Adverse Events (SAEs) and percentage of patients with AEs and SAEs (listed per grade and MedDRA (Medical Dictionary for Regulatory Activities ) preferred terms) will be reported.

  Continously for about 40 weeks plus follow-up

• Frequency of CD8 T cells specific for vaccinated APVAC peptides as measure of immunological response to and biological activity of the vaccine

  To analyze whether vaccinations with APVAC drug products plus poly-ICLC and GM-CSF induce immune responses in the patients. Peripheral blood mononuclear cells will be analyzed for the presence and functionality of T cells recognizing the peptides vaccinated within the individualized APVACs. * Immunogenicity rate: Number of vaccine induced T-cell responses normalized to the number of peptides vaccinated. * Immune responder rate: Number of patients with at least one vaccine induced T-cell response * Multi-TUMAP responder rate: Number of patients with at least two vaccine induced T-cell response * Average number of immune responses per patient

  Till 17 weeks of vaccination

Secondary Outcomes (3)

• Frequency of immune cell populations in the blood and concentrations of a large panel of serum and plasma proteins with immunological relevance as a measure of the immune status of the patient

  Up to 10 months

• Overall survival

  2018 (estimated)

• Progression-free survival

  At 6 months

Study Arms (1)

APVAC1 and 2 vaccine plus polyICLC and GMCSF concurrent to TMZ

EXPERIMENTAL

Drug: APVAC1 vaccine plus Poly-ICLC and GM-CSF; Drug: APVAC2 vaccine plus Poly-ICLC and GM-CSF

Interventions

APVAC1 vaccine plus Poly-ICLC and GM-CSF DRUG

APVAC1 vaccines (i.d.) will be individually assembled for each patient and can be applied to the patient approx. 3 months after enrollment. APVAC1 drug products are composed of 5 to 10 peptides from the GAPVAC warehouse. The APVAC1 vaccine will be applied concurrent to maintenance TMZ cycles after completion of chemoradiation therapy (CRT). Beginning on day 15 of the first maintenance TMZ cycle, patients will receive 11 vaccinations with APVAC1 drug products during 22 weeks. 578 μg per peptide per vial are used. Poly ICLC (1.5 mg s.c.) will be used as immunomodulator with all vaccinations except the second applications of APVAC1 (Day 2) and APVAC2 vaccines (Day 2\*) to avoid dose accumulation on consecutive days. The 2. immunomodulator GM-CSF (75 μg) will be applied i.d. with the first six vaccinations with both vaccines, APVAC1 and APVAC2. A total of 12 GM-CSF doses will be applied. GM-CSF will be applied to the APVAC vaccination site 10-30 min before injection of the APVACs.

Also known as: Actively Personalized Vaccine, Hiltonol, Leukine

APVAC1 and 2 vaccine plus polyICLC and GMCSF concurrent to TMZ

APVAC2 vaccine plus Poly-ICLC and GM-CSF DRUG

APVAC2 vaccines (i.d.) will be ready for use ca. 6 months after enrollment, as these peptides have to be newly synthesized for each patient following identification of the mutanome and corresponding mutated peptides in the HLA ligandome. APVAC2 drug products are composed of 1 or 2 peptides de novo synthesized for an individual patient. Patients will be repeatedly vaccinated with APVAC2 drug products beginning on day 15 of the 4. maintenance TMZ cycle. Patients will receive 8 vaccinations within 10 weeks. 578 μg per peptide per vial are used. Poly-ICLC (1.5 mg s.c.) will be used as immunomodulator with all vaccinations except the second applications of APVAC1 (Day 2) and APVAC2 vaccines (Day 2\*) to avoid dose accumulation on consecutive days. GM-CSF (75 μg) will be applied i.d. with the first six vaccinations with both vaccines, APVAC1 and APVAC2. A total of 12 GM-CSF doses will be applied. GM-CSF will be applied to the APVAC vaccination site 10-30 min before injection of the APVACs.

Also known as: Actively Personalized Vaccine, Hiltonol, Leukine

APVAC1 and 2 vaccine plus polyICLC and GMCSF concurrent to TMZ

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed, newly diagnosed GB (astrocytoma WHO grade IV)
• HLA phenotype defined by warehouse composition (HLA-A\*02:01 or HLA-A\*24:02 positive patients only; both as determined by a PCR-based 4-digit typing method)
• Gross total resection (as defined by less than 1 cm2 residual tumor mass on the largest perpendicular axes in post-operative scan taken within 48 h post-surgery; standard MRI conformable to the present national and international guidelines is sufficient)
• At least 0.5 g tumor tissue freshly cryopreserved during surgery
• Age ≥18 years
• KPS ≥70%
• Life expectancy \> 6 months
• Patient is a candidate for and willing to receive standard CRT 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 enrollment
• Absolute lymphocyte count (ALC) \>1.0 x109/L (re-screening of lymphocyte counts is allowed)
• Ability of subject to understand and the willingness to sign written informed consent for study participation. Written consent by a legally authorized representative is not sufficient.
• Availability of an APVAC analysis and manufacturing slot confirmed by the sponsor
• Female patients who are post-menopausal (no menstrual period for a minimum of 1 year), or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), practice one of the following medically acceptable methods of birth control (hormonal methods, intrauterine device or double-barrier methods) or practice total abstinence
• Male patients willing to use contraception (condoms with spermicidal jellies or cream) upon study entry and during the course of the study, have undergone vasectomy or are practicing total abstinence

You may not qualify if:

• Hemoglobin \< 10 g/dL (6.2 mmol/L)
• White blood cell count (WBC) decrease (\<3.0 x109/L) or increase (\>10.0 x109/L)
• Absolute neutrophil count (ANC) decrease \< 1.5 x109/L
• Platelet count decrease \< 75 x109/L
• Bilirubin \> 1.5 x ULN (upper limit of normal according to the performing lab's reference range)
• ALAT \> 3 x ULN
• ASAT \> 3 x ULN
• GGT6 \> 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).
• Prior therapy for glioma (except surgery and steroids) including but not limited to carmustine wafers and immunotherapy
• Any condition contraindicating leukapheresis from peripheral veins
• Concurrent participation in another interventional clinical trial studying a drug or treatment regimen.
• Clinically relevant autoimmune diseases (with the exception of thyroid diseases)
• Immunosuppression, not related to prior treatment for malignancy, or prior drug reaction

Sponsors & Collaborators

• Immatics Biotechnologies GmbH: lead
• BioNTech SE: collaborator
• University Hospital Tuebingen: collaborator
• BCN Peptides: collaborator
• EU-funded GAPVAC Consortium: collaborator

Study Sites (6)

Rigshospitalet, The Finsen Centre, Department of Oncology

Copenhagen, 2100, Denmark

Location

Neurologische Klinik & Nationales Centrum für Tumorerkrankungen Heidelberg

Heidelberg, 69120, Germany

Location

Zentrum für Neurologie und Klinik für Neurochirurgie

Tübingen, 72076, Germany

Location

Leiden University Medical Center, Department of Medical Oncology

Leiden, 2333ZA, Netherlands

Location

Vall d'Hebron University Hospital

Barcelona, 08035, Spain

Location

Hôpitaux Universitaires de Genève

Geneva, 1211, Switzerland

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

poly ICLC; Granulocyte-Macrophage Colony-Stimulating Factor; sargramostim

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

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Wolfgang Wick, Professor

  University of Heidelberg Medical Center

  PRINCIPAL INVESTIGATOR

• Pierre-Yves Dietrich, Professor

  University Hospital, Geneva

  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: May 16, 2014
• First Posted: May 29, 2014
• Study Start: October 1, 2014
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2018
• Last Updated: August 7, 2018

Record last verified: 2018-08

Locations

NL (1); DE (2); DK (1); ES (1); CH (1)