Evaluation of the Safety and Tolerability of i.v. Administration of a Cancer Vaccine in Patients With Advanced Melanoma (Lipo-MERIT)
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|ClinicalTrials.gov Identifier: NCT02410733|
Recruitment Status : Active, not recruiting
First Posted : April 8, 2015
Last Update Posted : December 29, 2021
|Condition or disease||Intervention/treatment||Phase|
|Melanoma||Biological: Lipo-MERIT||Phase 1|
- The Lipo-MERIT vaccine consists of four naked ribonucleic acid (RNA)-drug products (DPs) that are optimized to induce antigen-specific cluster of differentiation (CD)8+ and CD4+ T cell responses against the four selected malignant melanoma-associated antigens New York-ESO 1 (NY-ESO-1), tyrosinase, Melanoma-associated antigen A3 (MAGE-A3), and Trans-membrane phosphatase with tensin homology (TPTE).
- In this study, naked RNA DPs were formulated with liposomes to form RNA-lipoplexes (RNA-LPX) that (i) protect RNA from degradation in the serum, (ii) enable in vivo targeting of antigen-presenting cells (APC), and therefore (iii) constitute a novel vaccine formulation that supports intravenous administration. As of August 31, 2021 the RNA-DPs RBL001.1, RBL002.2, RBL003.1 and RBL004.1 initially used for treatment have been replaced by the improved RNA drug substances RBL001.3, RBL002.4, RBL003.3 and RBL004.3. These drug substances are formulated in lipoplexes to yield RNA-LPX (drug product). The added maximum duration of trial treatment with the new drug products is 18 months.
- The Lipo-MERIT vaccine is expected to lead to several effects contributing to its immunological (therapeutic) effect. First, the RNA-LPX home to APCs in lymphoid organs after intravenous injection, where they are rapidly taken up by professional APCs. Incorporated RNA is translocated to the cytoplasm leading to its translation by the host ribosome complex into four Antigen encoding proteins which are processed and presented on both Human leukocyte antigen (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, the Lipo-MERIT vaccine is expected to transiently activate APCs (change of surface marker expression and cytokine secretion) via signaling of Toll-like receptor (TLR)s, subsequently leading to the transient induction of inflammatory cytokines (such as Interferon (IFN)-α and Interferon gamma induced protein 10 [IP-10]) supporting the induction of tumor-antigen specific T cell responses.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||119 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Clinical First-in-human Dose Escalation Study Evaluating the Safety and Tolerability of Intravenous Administration of a Tetravalent RNA-lipoplex Cancer Vaccine Targeting the Tumor-associated Antigens NY-ESO-1, Tyrosinase, MAGE-A3, and TPTE in Patients With Advanced Melanoma|
|Actual Study Start Date :||March 2015|
|Estimated Primary Completion Date :||May 2023|
|Estimated Study Completion Date :||May 2023|
7 dose escalation cohorts (3 +3 design) and 3 expanded cohorts
- Number of Adverse Events as a Measure of safety and tolerability [ Time Frame: up to 8 years ]Number of patients with adverse events, total number of adverse events, dose limiting toxicities
- Objective response rate (ORR) [ Time Frame: up to 8 years ]ORR defined as the number of patients with complete responses (CR) or partial responses (PR) as best overall response according to Immune-related Response Evaluation Criteria in Solid Tumors criteria (irRECIST) divided by the number of patients in the efficacy analysis set.
- Disease control rate (DCR) [ Time Frame: up to 8 years ]DCR defined as the number of patients with CR or PR or stable disease (SD) as best overall response according to irRECIST divided by the number of patients in the efficacy analysis set.
- Duration of response (DoR) [ Time Frame: up to 8 years ]DoR defined as the time from initial response until first objective tumor progression according to irRECIST.
- Progression Free Survival (PFS) [ Time Frame: up to 8 years ]PFS defined as the time from the first vaccination to confirmed occurence of Progression or death from any course, which ever occurs first, per irRECIST.
- Overall survival (OS) [ Time Frame: up to 8 years ]OS defined as the time of first trial treatment until death from any cause.
- Change of induced T-cell responses for Lipo-MERIT vaccine from visit 2 (day 1) to day 71 (assessed by immunoassays) [ Time Frame: up to 8 years ]Vaccine induced T-cell responses assessed by immunoassays in 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): NCT02410733
|Johann Wolfgang Goethe Universität Frankfurt, Klinik für Dermatologie, Venerologie und Allergologie|
|Frankfurt, Germany, 60590|
|Universität Heidelberg, Dermatologie und NCT|
|Heidelberg, Germany, 69120|
|Universitätsmedizin Mainz, Hautklinik und Poliklinik|
|Mainz, Germany, 55131|
|Universitätsmedizin Mannheim, Klinik für Dermatologie, Venerologie und Allergologie|
|Mannheim, Germany, 68167|
|Study Director:||BioNTech Responsible Person||BioNTech SE|