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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

Phase 1
18 Years
Open (Enrolling)

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Trial Information

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

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.

Inclusion Criteria:

- Stage IIC, IIIA-C or unresectable stage IV of cutaneous melanoma (AJCC 2009 melanoma

- First line therapy for subjects not eligible or declining other first line therapies
after all available treatment options have been transparently disclosed (to be

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of adverse events

Outcome Description:

Number of Patients with adverse events, total number of adverse events, dose-limiting toxicities

Outcome Time Frame:

90 days

Safety Issue:


Principal Investigator

Ugur Sahin, Prof. Dr.

Investigator Role:

Study Director

Investigator Affiliation:

Ribological GmbH


Germany: Paul-Ehrlich-Institut

Study ID:




Start Date:

June 2012

Completion Date:

June 2014

Related Keywords:

  • Melanoma
  • RNA
  • Immuno Therapy
  • RB_0001-01
  • Ribological
  • Melanoma
  • RBL001
  • RBL002
  • cancer vaccine
  • Melanoma