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A Study to Evaluate Safety, Feasibility, Efficacy of Multiple Dosing With VB10.NEO Immunotherapy in Patients With Locally Advanced or Metastatic Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03548467
Recruitment Status : Recruiting
First Posted : June 7, 2018
Last Update Posted : June 25, 2018
Information provided by (Responsible Party):
Vaccibody AS

Brief Summary:
This open labelled first in human dose phase 1/2a study is designed to evaluate safety, feasibility and efficacy of multiple dosing with individualised VB10.NEO immunotherapy in patients with locally advanced or metastatic solid tumours.

Condition or disease Intervention/treatment Phase
Locally Advanced or Metastatic Solid Tumours Drug: VB10.NEO Phase 1 Phase 2

Detailed Description:

This open labelled first in human dose phase 1/2a study is designed to evaluate safety, feasibility and efficacy of multiple dosing with individualised VB10.NEO immunotherapy in patients with locally advanced or metastatic solid tumours including melanoma, non-small cell lung cancer (NSCLC), clear renal cell carcinoma, urothelial cancer or squamous cell carcinoma of the head and neck (SCCHN), who did not reach complete responses with immune checkpoint inhibitor (CPI) therapy as their standard of care (SOC) treatment.

Upon screening, the patients must have been receiving for at least 12 weeks a CPI (anti-PD-1 or anti-PD-L1) as the patient's standard of care, and according to currently approved indications. The VB10.NEO vaccine will be added to this continuing CPI treatment and shall not replace, omit, postpone or terminate the standard therapy. Patients will be enrolled in case of some benefit to CPI treatment is expected, as defined by partial remission, stable disease or disease progression (in case of a mixed response to CPI, provided at least one lesion shows measurable regression and patient, according to the investigator, would have a clinical benefit of continued immunotherapy).

The assumption is to combine the immuno-stimulating effect of CPIs with immune responses towards specific neo-antigens in the vaccine, which may possibly increase the anti-tumour effect to reach durable efficacy

The study will be conducted in two parts. Part A will evaluate safety, feasibility and efficacy of individualised VB10.NEO immunotherapy. The expansion part B will explore efficacy and safety in further patients with selected types of cancer showing signs of effect during part A.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 65 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Open Label
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Labelled First Human Dose Phase 1/2a Study to Evaluate Safety, Feasibility, Efficacy of Multiple Dosing With Individualised VB10.NEO Immunotherapy in Patients With Locally Advanced or Metastatic Melanoma, Non-small Cell Lung Cancer (NSCLC), Clear Renal Cell Carcinoma, Urothelial Cancer or Squamous Cell Carcinoma of Head and Neck, Who Did Not Reach Complete Responses With Current Standard of Care Immune Checkpoint Blockade
Actual Study Start Date : April 4, 2018
Estimated Primary Completion Date : January 2023
Estimated Study Completion Date : March 2023

Arm Intervention/treatment
Experimental: Open-Label
Treatment with individualized VB10.NEO immunotherapy will commence as soon as the patient-specific VB10.NEO vaccine is available and if the patient-specific vaccine meets all pre-specified product release criteria after manufacturing. The vaccinations will be given as intramuscular injection by the study personnel at the study centres.
Drug: VB10.NEO
VB10.NEO is a vaccine and is supplied as a sterile, ready to use solution (14 vaccinations will be given).

Primary Outcome Measures :
  1. Rate of Adverse Events including SAEs (Safety/tolerability) [ Time Frame: Up to 24 months ]
    Total number, severity (CTCAE grade) of adverse events(AEs), and if AE is leading to treatment discontinuation.

Secondary Outcome Measures :
  1. Immunogenicity by T-cell activity to each neoepitope of VB10.NEO immunotherapy [ Time Frame: Up to 24 months ]
    Descriptive analyses for each patient of of the immune-response to each neoepiotope

  2. Objective Response Rate (ORR) [ Time Frame: Up to 24 months ]
    Description of tumor response by iRECIST at regular intervals

  3. Duration of Response (DOR) [ Time Frame: Up to 24 months ]
    Descriptive analysis of DOR by iRECIST at regular intervals

  4. Progression-free survival (PFS) [ Time Frame: Up to 24 months ]
    Descriptive analysis of PFS by iRECIST at regular intervals

  5. Survival at end of treatment (EoT) and end of study (EoS) [ Time Frame: At 14 months and 24 months ]
    Proportion of patients who are live at EoT and EoS

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Have histologically confirmed locally advanced or metastatic melanoma, NSCLC, RCC, urothelial carcinoma or SCCHN.
  2. Patients must have been on CPI (i.e., anti-PD-1 or anti PD-L1) for at least 12 weeks before screening and must be on CPI treatment as part of their cancer treatment as prescribed by the treating physician.
  3. 18 years or older.
  4. Patients who as per RECIST at screening are:

    1. in partial response or;
    2. stable disease or,
    3. in progression, i.e., in case of a mixed response to CPI, provided at least one lesion shows measurable regression and who, according to the investigator, have a clinical benefit of continued immunotherapy.
  5. Adequate tumour specimen must be available for exome sequencing.
  6. Patients are eligible if progression occurs during the manufacturing process of the VB10.NEO vaccine.
  7. Patients who develop progressive disease under CPI after inclusion into the trial and discontinue CPI therapy have upon agreement with the sponsor and investigator the possibility to receive VB10.NEO once the manufacturing process of the vaccine is completed.
  8. Measurable disease per RECIST 1.1 criteria.
  9. ECOG performance status ≤ 1.
  10. Life expectancy at least 6 months in the best judgement of the investigator.
  11. Willing and able to sign a written informed consent form.

Exclusion Criteria:

  1. Ocular melanoma.
  2. Brain metastases (unless controlled and stable for at least 6 weeks) or leptomeningeal spread of disease.
  3. Positive serological test for hepatitis C virus or hepatitis B virus surface antigen (HBsAg) or human immunodeficiency virus (HIV).
  4. Other concomitant or prior malignant disease, except for adequately treated basal cell carcinoma or other nonmelanomatous skin cancer, low-grade urothelial cancer or other malignancies treated with curative intent within 2 or more years pre study entry and in complete remission at study entry.
  5. Active pre-existing autoimmune disease with the exception of: vitiligo, residual hypothyroidism due to autoimmune condition treated by hormone replacement, psoriasis.
  6. Immunosuppression including the continued use (> 7 days) of high-dose (>5 mg of prednisolone or equivalents) systemic steroids or the use of immunosuppressive agents for any concurrent condition. All systemically administered corticosteroids must be discontinued > 4 weeks prior to first study vaccine administration.
  7. Known allergy to aminoglycosides (especially kanamycin).
  8. Known immunodeficiency and/or immunosuppression.
  9. History of toxic shock syndrome.
  10. Evidence or history of clinically significant cardiac disease.
  11. Ongoing toxicity from prior therapy that is > grade 2 for skin toxicities and > grade 1 for all other toxicities, (National Cancer Institute (NCI) Common terminology criteria for adverse events, CTCAE version 4.0.), or that is progressing in severity, except toxicities not considered a safety risk (e.g., alopecia or fatigue).
  12. History of life threatening organ toxicity of grade 4 (CTCAE v. 4.0) related to CPI exposure, excluding endocrinopathies.
  13. Acute infections or fever.
  14. Tattoos, scars, or active lesions/rashes within 2 cm of the site of vaccination or any implantable leads.

    Current and prior treatment:

  15. Current participation in a clinical trial.
  16. Previous vaccination against infections within 30 days before study entry.
  17. Previous transplantations.

    Bone marrow function:

  18. Inadequate bone marrow function: Platelet count < 50,000/mcL.

    Anticoagulation therapy:

  19. Patients requiring therapeutic anticoagulation.

    Organ function:

  20. Inadequate liver function.
  21. Inadequate renal function.
  22. Clinically significant uncorrected electrolyte abnormalities (sodium, potassium, magnesium, phosphate) that are > CTCAE grade 3 for both low and high values).


  23. Female patients of childbearing potential not willing to use an effective form of contraception during treatment and for at least six months after the last dose of VB10.NEO.
  24. Pregnancy or intention to become pregnant during the study period.
  25. Nursing women.
  26. Evidence of any other medical conditions (such as psychiatric illness, infectious diseases, physical examination or laboratory findings) that may interfere with the study participation, affect patient compliance or place the patient at high risk from treatment-related complications.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03548467

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Contact: Hedda Wold +47 90997595

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Krankenhaus Nordwest gGmbH Recruiting
Frankfurt, Germany, 60488
Contact: Elke Jäger, PhD         
University Hospital Heidelberg, NCT, Im Neuenheimer Feld 460 Recruiting
Heidelberg, Germany, 69120
Contact: Jürgen Krauss, Dr.    +49-6221- 56 - 32837   
Contact: Jutta Schreiber   
Klinik und Poliklinik für Innere Medizin III, Hämatologie und Onkologie Recruiting
Munich, Germany, 81675
Contact: Angela Krackhardt, PhD         
Sponsors and Collaborators
Vaccibody AS
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Study Director: Mads Axelsen, MD Sponsor GmbH

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Responsible Party: Vaccibody AS Identifier: NCT03548467     History of Changes
Other Study ID Numbers: VB N-01
First Posted: June 7, 2018    Key Record Dates
Last Update Posted: June 25, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Vaccibody AS:
clear renal cell carcinoma
urothelial cancer or SCCHN

Additional relevant MeSH terms:
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Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms by Site
Carcinoma, Squamous Cell
Head and Neck Neoplasms