RNA-Immunotherapy of IVAC_W_bre1_uID and IVAC_M_uID (TNBC-MERIT)
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|ClinicalTrials.gov Identifier: NCT02316457|
Recruitment Status : Active, not recruiting
First Posted : December 15, 2014
Last Update Posted : January 18, 2020
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer (Triple Negative Breast Cancer (TNBC))||Biological: IVAC_W_bre1_uID Biological: IVAC_W_bre1_uID/IVAC_M_uID||Phase 1|
- The IVAC® WAREHOUSE concept is based on RNA drug products shelved in a warehouse and targeting shared tumour-associated antigens (TAAs). The BioNTech Group (henceforward the "company") has identified a set of target antigens commonly expressed in TNBC. The selected breast cancer-associated antigens have been shown by immunogenicity testing to constitute suitable targets for immunotherapy and form the basis for the development of a novel RNA-based immunotherapy approach.
- The IVAC® MUTANOME concept is based on the identification of tumour-specific mutations by next-generation sequencing (NGS) and on-demand RNA manufacturing for use in single patients to target multiple neo-antigens derived from mutated epitopes. The novel therapeutic concept is supported by a series of research projects and high level publications that have led to a broad acceptance that mutation-specific T cells bear enormous potential to confer anti-tumoural activity in cancer patients1-5.
- The TNBC-MERIT study will introduce the novel therapeutic concept for the individualized treatment of breast cancer that is based on (i) treatment with a patient-specific liposome complexed RNA tailored to the antigen-expression profile of any given patient's tumour (IVAC® WAREHOUSE immunotherapy - IVAC_W_bre1_uID) and (ii) on treatment with de novo synthesized RNAs targeting up to 20 individual tumour mutations (IVAC® MUTANOME immunotherapy - IVAC_M_uID) following treatment with IVAC® WAREHOUSE. The scientific rationale for the combination of the two IVAC® approaches is based on the assumption that immunotherapies that (1) acknowledge tumour heterogeneity on a single-patient level and (2) target the whole range of antigens selectively expressed on tumours ("cancer antigenome"), including immunogenic shared and unique antigens, bear the highest potential to constitute an effective treatment of tumours.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||39 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||First-in-human Clinical Study With RNA-Immunotherapy Combination of IVAC_W_bre1_uID and IVAC_M_uID for Individualized Tumour Therapy in Triple Negative Breast Cancer Patients|
|Actual Study Start Date :||October 2016|
|Estimated Primary Completion Date :||June 2020|
|Estimated Study Completion Date :||November 2020|
Experimental: ARM1 IVAC_W_bre1_uID
Patients enrolled in ARM1 will receive a treatment with four RNAs. This includes two to three variant RNAs selected from the IVAC®WAREHOUSE plus p53 RNA. The selection process of RNAs from the warehouse is based on RT-PCR-based profiling of RNA extracted from patient tumour sample specimens, pre-defined cut-offs and algorithms to select the three relevant RNAs for a given patient.
Experimental: ARM2 IVAC_W_bre1_uID/IVAC_M_uID
Patients enrolled in ARM2 will optionally receive the IVAC®WAREHOUSE treatment as described above followed by the personalized IVAC® MUTANOME immunotherapy. The mutation selection process constitutes a multi-step process including identification of somatic mutations by NGS, mutation confirmation and prioritization, selection, and on demand manufacturing.
Experimental: ARM3 IVAC_W_bre1_uID + RBLTet.1
Patients enrolled in ARM3 will receive a treatment with four RNAs. This includes two to three variant RNAs selected from the IVAC®WAREHOUSE plus p53 RNA. The selection process of RNAs from the warehouse is based on RT-PCR-based profiling of RNA extracted from patient tumour sample specimens, pre-defined cut-offs and algorithms to select the three relevant RNAs for a given patient. RBLTet.1 RNA will be added to each RNA applied.
- Number of Adverse Events as a Measure of Safety and Tolerability of IVAC_W_bre1_uID [ Time Frame: day 90 ]Assessment of AEs
- Number of Adverse Events as a Measure of Safety and Tolerability of IVAC_W_bre1_uID plus IVAC_M_uID [ Time Frame: average on day 196 ]Assessment of AEs, End of treatment visit is depending on treatment schedule
- Change of induced T-cell responses for IVAC_W_bre_uID change from Visit 1 to V9 [ Time Frame: an average of 71 days ]Vaccine induced T-cell responses assessed by immuno assays in peripheral blood and skin
- Change of induced T-cell responses for IVAC_M_uID change from Visit 12 to V18 [ Time Frame: an average of 50 days ]Vaccine induced T-cell responses assessed by immuno assays in peripheral blood and skin
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 ClinicalTrials.gov identifier (NCT number): NCT02316457
|Johannes Gutenberg University|
|Mainz, RLP, Germany, 55131|
|National Center for Tumor Diseases (NCT)|
|Heidelberg, Germany, 69120|
|Dr. Horst Schmidt-Kliniken Wiesbaden|
|Wiesbaden, Germany, 65199|
|Uppsala University Hospital|
|Uppsala, Sweden, 75185|
|Study Director:||Ugur Sahin, Prof. Dr.||BioNTech SE|