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RBL001/RBL002 Phase I Clinical Trial (MERIT)

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: NCT01684241
Recruitment Status : Completed
First Posted : September 12, 2012
Last Update Posted : January 18, 2020
Information provided by (Responsible Party):
BioNTech SE ( BioNTech RNA Pharmaceuticals GmbH )

Brief Summary:
Clinical first-in-human dose escalation study evaluating the safety and tolerability of intranodal administration of an RNA-based cancer vaccine targeting two tumor-associated antigens in patients with advanced melanoma

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

Detailed Description:

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

The Targeted 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 approach and determine vaccine target antigen directed immune responses as early biomarkers for clinical mode of action.

The RBL001/RBL002 vaccine is expected to lead to several effects contributing to its immunological (therapeutic) effect. First, ultrasound guided administration of naked RNA drug product into lymph nodes is expected to result in rapid uptake of naked RNA by lymph node resident professional antigen-presenting cells (APCs). Incorporated RNA is known to translocate to the cytoplasm leading to its translation by the host ribosome complex into the respective protein antigens. The recombinant vaccine is optimized for immunogenicity and enables presentation of diverse antigenic epitopes on both HLA-class I as well as HLA-class II molecules. Consecutively, antigen-specific CD8+ and CD4+ T cell responses will be triggered by HLA-peptide complexes on the surface of antigen presenting cells. In addition, RNA administration will also lead to transient activation (change of surface marker expression and cytokine secretion) of APCs in the targeted lymph nodes particularly via signaling of TLR 7 and 8 leading to an adjuvant effect, supporting the induction of target-specific T cell responses with systemic anti-tumor activity.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 29 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Clinical First-in-human Dose Escalation Study Evaluating the Safety and Tolerability of Intranodal Administration of an RNA-based Cancer Vaccine Targeting Two Tumor-associated Antigens in Patients With Advanced Melanoma
Study Start Date : June 2012
Actual Primary Completion Date : May 2015
Actual Study Completion Date : July 2015

Resource links provided by the National Library of Medicine

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

Arm Intervention/treatment
Experimental: RBL001/RBL002 intranodal administration

All participants will be treated with RBL001/RBL002 after allocation to one of the four escalating dose cohorts:

  • Cohort-1 50 µg RBL001 and 50 µg RBL002
  • Cohort-2 100 µg RBL001 and 100 µg RBL002
  • Cohort-3 300 µg RBL001 and 300 µg RBL002
  • Cohort-4 600 µg RBL001 and 600 µg RBL002
Biological: RBL001/RBL002
Each participant will receive 8 repeated intranodal administrations of RBL001 and RBL002 during a time frame of 43 to 51 days.
Other Name: cancer vaccine

Primary Outcome Measures :
  1. Number of adverse events [ Time Frame: 90 days ]
    Number of Patients with adverse events, total number of adverse events, dose-limiting toxicities

Secondary Outcome Measures :
  1. Determination of antitumoral immune responses [ Time Frame: 90 days ]
    Cellular immune responses, cytokines, AB responses, serum biomarkers, and further immunological parameters will be determined once or repeatedly in the course of treatment. In the latter case changes from baseline will be tabulated.

  2. Clinical Monitoring of Tumor Lesions [ Time Frame: 90 days ]
    Tumor lesion status as determined by CT or MRI results evaluated by irRC and RECIST.

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

Inclusion Criteria:

  • Stage IIC, IIIA-C or unresectable stage IV of cutaneous melanoma (AJCC 2009 melanoma classification)
  • 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!)
  • Antigen expression confirmed by RT-PCR analysis from FFPE
  • ≥ 18 years of age
  • Written informed consent (part I and part II)
  • ECOG performance status (PS) 0-1 or Karnofsky Index 70-100 %
  • Life expectancy > 3 months
  • WBC ≥ 3x109/L
  • Hemoglobin ≥ 10 g/dl
  • Platelet count ≥ 100,000/mm³
  • LDH level < 2.0 x ULN
  • Negative pregnancy test (measured by β-HCG) for females of childbearing age
  • Suitable lymph nodes for injection using ultrasound guidance

Exclusion Criteria:

  • Pregnancy or breastfeeding
  • Primary ocular melanoma
  • Presence of 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
  • Acute or chronic active hepatitis B or C infection, EBV or CMV
  • Receipt of allogenic stem cell transplantation
  • 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, chemotherapy, major surgery, immunotherapy, vaccination, any other concurrent anticancer therapy or any investigational drug within 28 days before the first treatment of this study
  • Minor surgery within 14 days before the first treatment of this study
  • Treatment with Ipilimumab within 84 days before the first treatment of this study
  • Fertile males and females who are unwilling to employ adequate means of contraception (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): NCT01684241

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Medizinische Universität Wien, Abteilung für Dermatologie
Vienna, Austria, A-1090
Medizinische Fakultät der Universität Duisburg-Essen
Essen, Germany, 45122
Universtitätsmedizin der Johannes-Gutenberg Universtität
Mainz, Germany, 55131
Universitätsklinik Mannheim
Mannheim, Germany
Sponsors and Collaborators
BioNTech RNA Pharmaceuticals GmbH
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Study Director: Ugur Sahin, Prof. Dr. Ribological GmbH
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Responsible Party: BioNTech RNA Pharmaceuticals GmbH Identifier: NCT01684241    
Other Study ID Numbers: RB_0001-01
First Posted: September 12, 2012    Key Record Dates
Last Update Posted: January 18, 2020
Last Verified: January 2020
Keywords provided by BioNTech SE ( BioNTech RNA Pharmaceuticals GmbH ):
Biontech RNA Pharmaceuticals GmbH
Biontech RNA
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