RBL001/RBL002 Phase I Clinical Trial (MERIT)
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 Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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|
- Number of adverse events [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]Number of Patients with adverse events, total number of adverse events, dose-limiting toxicities
- Determination of antitumoral immune responses [ Time Frame: 90 days ] [ Designated as safety issue: No ]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.
- Clinical Monitoring of Tumor Lesions [ Time Frame: 90 days ] [ Designated as safety issue: No ]Tumor lesion status as determined by CT or MRI results evaluated by irRC and RECIST.
|Study Start Date:||June 2012|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||June 2014 (Final data collection date for primary outcome measure)|
Experimental: RBL001/RBL002 intranodal administration
All participants will be treated with RBL001/RBL002 after allocation to one of the four escalating dose cohorts:
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
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.
|Contact: Alexandra Kemmer-Brueck||+49 6131 63580 ext 0||Alexandra.Kemmer-Brueck@biontech.de|
|Contact: Cedrik M Britten, Dr.||+49 6131 63580 ext 0||Cedrik.Britten@biontechrna.de|
|Medizinische Universität Wien, Abteilung für Dermatologie||Recruiting|
|Vienna, Austria, A-1090|
|Contact: Christoph Hoeller, Prof. Dr.|
|Principal Investigator: Christoph Höller, Prof. Dr.|
|Medizinische Fakultät der Universität Duisburg-Essen||Recruiting|
|Essen, Germany, 45122|
|Contact: Dirk Schadendorf, Prof. Dr.|
|Principal Investigator: Dirk Schadendorf, Prof. Dr.|
|Universtitätsmedizin der Johannes-Gutenberg Universtität||Recruiting|
|Mainz, Germany, 55131|
|Contact: Carmen Loquai, Dr.|
|Principal Investigator: Carmen Loquai, PD Dr.|
|Contact: Jochen Utikal, Prof. Dr.|
|Principal Investigator: Jochen Utikal, Prof. Dr.|
|Study Director:||Ugur Sahin, Prof. Dr.||Biontech RNA Pharmaceuticals GmbH|