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IVAC MUTANOME Phase I Clinical Trial

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. Read our disclaimer for details. Identifier: NCT02035956
Recruitment Status : Completed
First Posted : January 14, 2014
Last Update Posted : January 18, 2020
Information provided by (Responsible Party):
BioNTech SE ( BioNTech RNA Pharmaceuticals GmbH )

Brief Summary:
Clinical first-in-human study evaluating the safety, tolerability and immunogenicity of intra-nodal administration of a personalized vaccination with IVAC MUTANOME vaccine with or without initial treatment with RBL001/RBL002 vaccine in patients with advanced melanoma

Condition or disease Intervention/treatment Phase
Melanoma Biological: IVAC MUTANOME, RBL001/RBL002 Phase 1

Detailed Description:

IVAC MUTANOME is a poly-neo-epitopic coding RNA vaccine targeting the unique mutation signature of an individual patient. It is engineered on demand, provided as two patient-specific RNA drug products and administered as an individual treatment.

RBL001/RBL002 and IVAC MUTANOME are naked ribonucleic acid (RNA) based recombinant vaccines optimized to induce antigen-specific CD8+ and CD4+ T cell responses against melanoma associated target antigens.

The two antigens are well characterized antigens in melanoma that have been previously utilized with excellent safety and proven immunogenicity as vaccine targets in a number of independent clinical trials.

The overall rationale of the study is to determine safety of the novel RNA-based vaccine strategy and determine the number and function of vaccine-induced antigen-specific immune-responses as early biomarkers for the clinical mode of action.

The IVAC MUTANOME vaccine approach is based on targeting multiple immunogenic tumour mutations unique to a given patient's tumour using a poly-epitopic RNA-based vaccine manufactured for use in a single patient only. Parallel to the target discovery process and on demand manufacturing of IVAC MUTANOME vaccine patients with RBL001 and/ or RBL002 positive-tumours will receive the RBL001/RBL002 vaccine. Patients which tumours that are RBL001 and RBL002 negative can also be included into the clinical study but will not receive RBL001/RBL002 prior to IVAC MUTANOME. Applying this approach the RBL001/RBL002 vaccine and the IVAC MUTANOME vaccine administration is expected to lead to several effects contributing to their immunological (therapeutic) effects.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: First-in-human Study Evaluating the Safety, Tolerability and Immunogenicity of i.n. Administration of a Personalized Vaccination With IVAC MUTANOME Vaccine w/o Initial Treatment With RBL001/RBL002 Vaccine in Patients With Advanced Melanoma
Actual Study Start Date : December 2013
Actual Primary Completion Date : February 14, 2017
Actual Study Completion Date : October 2019

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma Vaccines

Arm Intervention/treatment
Experimental: IVAC MUTANOME RBL001/RBL002
All participants will be treated with the personalized IVAC MUTANOME vaccine with or without prior treatment with RBL001/RBL002 vaccine depending on expression of these two antigens. Vaccines will be administered intra-nodally.
Biological: IVAC MUTANOME, RBL001/RBL002
Each patient will receive multiple repeated intranodal injections of IVAC MUTANOME vaccine with or without initial treatment with RBL001/RBL002.
Other Name: cancer vaccine

Primary Outcome Measures :
  1. Safety and tolerability of repetitive doses [ Time Frame: up to a maximum of 189 days ]
    Number of Patients with adverse events, total number of adverse events

Secondary Outcome Measures :
  1. Monitoring of vaccine-induced cellular immune response, [ Time Frame: 161 days ]
    Determination of pharmacodynamic activity

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Malignant Melanoma, resectable stage IIIA-C and IV (AJCC 2009 melanoma classification)
  • Patients with unresectable Malignant Melanoma stage IIIA-C in complete remission, partial remission or stable disease after treatment with vemurafenib or patients with slow progressive disease.
  • Malignant Melanoma, unresectable stage IV (AJCC 2009 melanoma classification) in complete remission, partial remission or stable disease after treatment with vemurafenib
  • All lines of treatment for malignant melanoma are accepted.
  • First line therapy for subjects not eligible or declining other first line therapies after all available treatment options have been transparently disclosed (to be documented in patient medical record).
  • ≥ 18 years of age
  • Written informed consent
  • ECOG performance status (PS) 0-1 (appendix G)
  • Life expectancy > 6 months
  • WBC ≥ 3x109/L
  • Haemoglobin ≥ 10 g/dl
  • Platelet count ≥ 100,000/mm³
  • LDH level < 2.0 x ULN
  • Negative pregnancy test (measured by β-HCG) for females which are childbearing potential
  • Suitable lymph nodes for injection using ultrasound guidance

Exclusion Criteria:

  • Pregnancy or breastfeeding
  • Primary ocular melanoma
  • History (< 5 years) of a second malignancy other than squamous or basal cell carcinoma, non-active prostate cancer or cervical carcinoma in situ
  • Brain metastases
  • Known or symptomatic pleural effusions and/or ascites
  • Known hypersensitivity to the active substance or to any of the excipients
  • A serious local infection (e.g. cellulitis, abscess) or systemic infection (e.g. pneumonia, septicemia) which requires systemic antibiotic treatment within 2 weeks prior to the first dose of study medication
  • Positive test for acute or chronic active hepatitis B or C infection, acute EBV or acute CMV injection
  • Clinically relevant autoimmune disease
  • Systemic immune suppression:
  • HIV disease
  • Use of chronic oral or systemic steroid medication (topical or inhalational steroids are permitted)
  • Other clinical relevant systemic immune suppression
  • Symptomatic congestive heart failure (NYHA 3 or 4)
  • Unstable angina pectoris
  • Radiotherapy within two weeks, myelosuppressive chemotherapy, ipilimumab and major surgery within 4 weeks/28 days before the first treatment. Interferon and approved BRAF inhibitors will be allowed as concurrent treatment.
  • Any investigational drug within 4 weeks/28 days or 5 half-lives depending on what gives the longer range before the first treatment of this study
  • Minor surgery within 14 days before the first treatment of this study
  • Fertile males and females who are unwilling to use a highly effective method of birth control (less than 1% per year, e.g. condom with spermicide, diaphragm with spermicide, birth control pills, injections, patches or intrauterine device) during study treatment and 28 days after the last dose of study treatment
  • Presence of a serious concurrent illness or other condition (e.g. psychological, family, sociological, or geographical circumstances) that does not permit adequate follow-up and compliance with the protocol

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): NCT02035956

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Medizinische Universität Wien
Wien, AT-Wien, Austria, 1090
Hautklinik und Poliklinik Universitätsmedizin der Johannes-Gutenberg Universität Mainz
Mainz, Germany, 55131
Klinik für Dermatologie, Venerologie und Allergologie UMM - Universitätsmedizin Mannheim Medizinische Fakultät Mannheim der Ruprecht-Karls-Universität Heidelberg
Mannheim, Germany, 68167
Sponsors and Collaborators
BioNTech RNA Pharmaceuticals GmbH
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Study Director: Ugur Sahin, Prof. Dr. BioNTech RNA Pharmaceuticals GmbH
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: BioNTech RNA Pharmaceuticals GmbH Identifier: NCT02035956    
Other Study ID Numbers: RB_0004-01
First Posted: January 14, 2014    Key Record Dates
Last Update Posted: January 18, 2020
Last Verified: January 2020
Keywords provided by BioNTech SE ( BioNTech RNA Pharmaceuticals GmbH ):
personalized therapy
personalized immuno therapy
cancer vaccine
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Immunologic Factors
Physiological Effects of Drugs