Ignite Creation Date:
2025-12-25 @ 2:54 AM
Ignite Modification Date:
2026-03-01 @ 9:33 AM
Study NCT ID:
NCT02410733
Status:
COMPLETED
Last Update Posted:
2023-07-19
First Post:
2015-03-24
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Evaluation of the Safety and Tolerability of i.v. Administration of a Cancer Vaccine in Patients With Advanced Melanoma
Sponsor:
BioNTech SE
Organization:
Study Overview
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
Status:
COMPLETED
Status Verified Date:
2023-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Lipo-MERIT
Brief Summary:
The purpose of this study is to determine the safety and tolerability of intravenous administration of a tetravalent RNA-lipoplex cancer vaccine targeting four tumor-associated antigens in patients with advanced melanoma.
Detailed Description:
* 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 As of August 31, 2021 the RNA-DPs RBL001.1, RBL002.2, RBL003.1 and RBL004.1 initially used for treatment have been replaced by the improved RNA drug substances RBL001.3, RBL002.4, RBL003.3 and RBL004.3.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.
* 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 Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 2013-001646-33 | EUDRACT_NUMBER | None | View |