MelanomaPhase 1Lipo-MERITNCT02410733
Evaluation of the Safety and Tolerability of i.v. Administration of a Cancer Vaccine in Patients With Advanced Melanoma
A Phase 1 study testing Lipo-MERIT in people with Melanoma, run by BioNTech SE at 4 sites in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- Lipo-MERIT
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 119 participants
- Where
- 4 sitesGermany
- Study dates
- Mar 2015to 20 Jun 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Cohort I: stage IV malignant melanoma (American joint committee on cancer (AJCC) 2009 melanoma classification)
- Cohorts II-VII and expanded cohorts: stage IIIB-C, or stage IV of malignant melanoma (AJCC 2009 melanoma classification) [only applicable until approval of protocol version 10.0] Expanded cohort C only patients with stage IV melanoma (AJCC 2009 melanoma classification) with measurable disease (at least one target lesion according irRECIST) [applicable for all patients included after approval of protocol version 10.0 and higher] and with disease progression at the time of first treatment with Investigational medicinal product (IMP) [applicable for all patients included after approval of protocol version 11.0]
- Therapy only for subjects not eligible or declining any other available approved therapy after all available treatment options have been transparently disclosed (to be documented!)
- Expression of either NY-ESO-1, tyrosinase, MAGE-A3, and/or TPTE confirmed by RT-qPCR analysis from formalin-fixed paraffin-embedded (FFPE)
- ≥ 18 years of age
- Written informed consent
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- Eastern cooperative oncology group (ECOG) performance status (PS) 0-1
- Life expectancy ≥ 6 months
- White blood cell (WBC) ≥ 3x10^9/L
- Hemoglobin ≥ 9 g/dL
- Platelet count ≥ 100,000/mm^3
- Alanine aminotransferase/Aspartate aminotransferase (ALT/AST) < 3 x upper limit of normal (ULN) (except patients with liver metastasis)
- Negative pregnancy test (measured by Human chorionic gonadotropin [β-HCG]) for females with childbearing age
Who cannot join
- Pregnancy or breastfeeding
- Primary ocular melanoma
- Concurrence of a second malignancy other than squamous or basal cell carcinoma, non-active prostate cancer, or cervical carcinoma in situ or non-active treated urothelial carcinoma
- Brain metastases
- Patients with history of treated or inactive brain metastasis are eligible for treatment in expanded cohort C, provided they meet all of the following criteria:
- measurable disease outside of the brain (in addition to inactive brain metastasis);
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- no ongoing requirement of corticosteroids as therapy for brain metastases,
- with corticosteroids discontinued ≥1 week prior to visit 2 (day 1) with no ongoing symptoms attributable to brain metastasis;
- the screening brain radiographic imaging is ≥ 4 weeks since completion of radiotherapy
- Post-splenectomy Patients
- 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
- Positive test for acute or chronic active hepatitis B or C infection
- Clinically relevant active autoimmune disease
- Systemic immune suppression:
- Human immunodeficiency virus (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 and minor surgery within 14 days prior to the first study treatment administration
- Myelosuppressive chemotherapy within 14 days and after reconstitution of blood values prior to the first study treatment administration
- Ipilimumab within 28 days prior to the first study treatment administration
- Treatments with BRAF inhibitors, MEK inhibitors, or the combination of both, and anti-programmed death-1 (PD-1) antibodies within 14 days prior to the first administration of study treatment (not applicable for patients with parallel treatment in expanded cohorts A, B, or C at the discretion of the investigator)
- Interferon, major surgery, vaccination, and other investigational agents within 28 days or 5 half-lives depending on what gives the longer range before the first treatment
- Approved BRAF inhibitors vemurafenib or dabrafenib, approved anti-PD-1 inhibitors nivolumab or pembrolizumab as well as approved MEK inhibitor trametinib, or the approved combination of BRAF-MEK inhibitors in patients in dose escalation cohorts. Concomitant treatment with approved BRAF inhibitors, approved anti-PD-1 antibodies or MEK inhibitor as well as the approved combination of BRAF-MEK inhibitors is allowed for patients included in the expanded cohorts, after analysis of safety data collected for the dose escalation cohorts and data and safety monitoring board (DSMB) approval. Local radiation will be allowed as concurrent treatment for patients in expanded cohort as well.
- After approval of protocol version 10.0 and higher only anti-PD-1 antibodies are allowed for treatment of patients in expanded cohort C.
- Fertile males and females who are unwilling to use a highly effective method of birth control (less than 1% per year, e.g. condom with spermicide, diaphragm with spermicide, birth control pills, injections, patches or intrauterine device) during study treatment and for at least 28 days (male patients) and 90 days (female patients of childbearing potential) after the last dose of study treatment
- Presence of a severe 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
Trial locations and contacts
4 sites in 1 country.
Germany4 sites
Johann Wolfgang Goethe Universität Frankfurt, Klinik für Dermatologie, Venerologie und Allergologie
Frankfurt, 60590
Universität Heidelberg, Dermatologie und NCT
Heidelberg, 69120
Universitätsmedizin Mainz, Hautklinik und Poliklinik
Mainz, 55131
Universitätsmedizin Mannheim, Klinik für Dermatologie, Venerologie und Allergologie
Mannheim, 68167
About this study
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
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.
Read the 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.
- Conditions
- Melanoma
- Being tested
- Lipo-MERIT
- Keywords
- melanoma, Lipo-MERIT, cancer vaccine, RB_0003-01, BioNTech, BioNTech SE, BioNTech RNA, RNA, RNA vaccine, BNT111
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lipo-MERITBiological
vaccination
| Study group | Role | What they receive |
|---|---|---|
| Lipo-MERIT | Experimental | 7 dose escalation cohorts (3 +3 design) and 3 expanded cohorts Receives: Biological: Lipo-MERIT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Adverse Events as a Measure of safety and tolerability
Number of patients with adverse events, total number of adverse events, dose limiting toxicities
Measured: up to 8 years
Secondary outcomes (6)
Objective response rate (ORR)
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.
Measured: up to 8 years
Disease control rate (DCR)
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.
Measured: up to 8 years
Duration of response (DoR)
DoR defined as the time from initial response until first objective tumor progression according to irRECIST.
Measured: up to 8 years
Progression Free Survival (PFS)
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.
Measured: up to 8 years
Overall survival (OS)
OS defined as the time of first trial treatment until death from any cause.
Measured: up to 8 years
Change of induced T-cell responses for Lipo-MERIT vaccine from visit 2 (day 1) to day 71 (assessed by immunoassays)
Vaccine induced T-cell responses assessed by immunoassays in skin.
Measured: up to 8 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2015 (estimated)
- Study startMar 2015
- Primary completion20 Jun 2023
- Study completion20 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by BioNTech SEThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 119 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioNTech SE
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- BioNTech Responsible Person, Study director, BioNTech SE
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02410733
- Sponsor's protocol ID
- RB_0003-01
- Other IDs
- 2013-001646-33
- Acronym
- Lipo-MERIT
- Status last verified
- Mar 2026
- First submitted
- 24 Mar 2015
- Last updated
- 12 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Sahin U, Oehm P, Derhovanessian E, Jabulowsky RA, Vormehr M, Gold M, Maurus D, Schwarck-Kokarakis D, Kuhn AN, Omokoko T, Kranz LM, Diken M, Kreiter S, Haas H, Attig S, Rae R, Cuk K, Kemmer-Bruck A, Breitkreuz A, Tolliver C, Caspar J, Quinkhardt J, Hebich L, Stein M, Hohberger A, Vogler I, Liebig I, Renken S, Sikorski J, Leierer M, Muller V, Mitzel-Rink H, Miederer M, Huber C, Grabbe S, Utikal J, Pinter A, Kaufmann R, Hassel JC, Loquai C, Tureci O. An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma. Nature. 2020 Sep;585(7823):107-112. doi: 10.1038/s41586-020-2537-9. Epub 2020 Jul 29.
PubMed 32728218
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02410733
- Acronym / sponsor ID
- Lipo-MERIT / RB_0003-01
- Conditions
- Melanoma
- Keywords
- melanoma, Lipo-MERIT, cancer vaccine, RB_0003-01, BioNTech, BioNTech SE, BioNTech RNA, RNA
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 119 participants (actual)
- Lead sponsor
- BioNTech SEIndustry (pharma, biotech, devices)
- Study start
- Mar 2015 (actual)
- Primary completion
- 20 Jun 2023 (actual)
- Study completion
- 20 Jun 2023 (actual)
- First posted
- 8 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lipo-MERIT | Experimental | Biological: Lipo-MERIT7 dose escalation cohorts (3 +3 design) and 3 expanded cohorts |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Cohort I: stage IV malignant melanoma (American joint committee on cancer (AJCC) 2009 melanoma classification)
- Cohorts II-VII and expanded cohorts: stage IIIB-C, or stage IV of malignant melanoma (AJCC 2009 melanoma classification) [only applicable until approval of protocol version 10.0] Expanded cohort C only patients with stage IV melanoma (AJCC 2009 melanoma classification) with measurable disease (at least one target lesion according irRECIST) [applicable for all patients included after approval of protocol version 10.0 and higher] and with disease progression at the time of first treatment with Investigational medicinal product (IMP) [applicable for all patients included after approval of protocol version 11.0]
- Therapy only for subjects not eligible or declining any other available approved therapy after all available treatment options have been transparently disclosed (to be documented!)
- Expression of either NY-ESO-1, tyrosinase, MAGE-A3, and/or TPTE confirmed by RT-qPCR analysis from formalin-fixed paraffin-embedded (FFPE)
- ≥ 18 years of age
Key exclusion criteria (29 listed)
- Pregnancy or breastfeeding
- Primary ocular melanoma
- Concurrence of a second malignancy other than squamous or basal cell carcinoma, non-active prostate cancer, or cervical carcinoma in situ or non-active treated urothelial carcinoma
- Brain metastases
- Post-splenectomy Patients
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lipo-MERITvaccination | Biological | Lipo-MERIT |
Primary outcome
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
6 secondary outcomes
Objective response rate (ORR)
Time frame: up to 8 years
Disease control rate (DCR)
Time frame: up to 8 years
Duration of response (DoR)
Time frame: up to 8 years
Progression Free Survival (PFS)
Time frame: up to 8 years
Overall survival (OS)
Time frame: up to 8 years
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2026.
- Derived from this study: PubMed 32728218Sahin U, Oehm P, Derhovanessian E, Jabulowsky RA, Vormehr M, Gold M, Maurus D, Schwarck-Kokarakis D, Kuhn AN, Omokoko T, Kranz LM, Diken M, Kreiter S, Haas H, Attig S, Rae R, Cuk K, Kemmer-Bruck A, Breitkreuz A, Tolliver C, Caspar J, Quinkhardt J, Hebich L, Stein M, Hohberger A, Vogler I, Liebig I, Renken S, Sikorski J, Leierer M, Muller V, Mitzel-Rink H, Miederer M, Huber C, Grabbe S, Utikal J, Pinter A, Kaufmann R, Hassel JC, Loquai C, Tureci O. An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma. Nature. 2020 Sep;585(7823):107-112. doi: 10.1038/s41586-020-2537-9. Epub 2020 Jul 29.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
BioNTech Responsible Person study director
BioNTech SE
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Lipo-MERIT in people with Melanoma, run by BioNTech SE at 4 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Adverse Events as a Measure of safety and tolerability (time frame: up to 8 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02410733, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2026.