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Solid TumorPhase 1NCT04503278

A Clinical Study of the Safety and Effectiveness of an Investigational Cell Therapy Given With and Without an Investigational RNA-based Vaccine in Patients With Organ Tumors

A Phase 1 study testing CLDN6 CAR-T and CLDN6 uRNA-LPX/CLDN6 modRNA-LPX in people with Solid Tumor, run by BioNTech Cell & Gene Therapies GmbH at 12 sites in 4 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This is a Phase I, FIH, open-label, multi-site, dose escalation trial with expansion cohorts to evaluate safety and preliminary efficacy of claudin 6 (CLDN6) chimeric antigen receptor T cells (CAR-T) with or without CLDN6 ribonucleic acid lipoplexes (RNA-LPX) in patients with CLDN6-positive relapsed or refractory… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumor
What is being tested?
CLDN6 CAR-T and CLDN6 uRNA-LPX/CLDN6 modRNA-LPX
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
214 participants
Where
12 sitesin 4 countries
Study dates
16 Sep 2020to Aug 2041
Phase
Phase 1
Are there results?
Not yet: the study is under way

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

  • Each patient enrolled in the trial must have CLDN6-positive tumor regardless of tumor histology defined as ≥ 50% of tumor cells expressing CLDN6 protein at an intensity of ≥2+ using a semi-quantitative immunohistochemistry assay in a central laboratory for specific detection of CLDN6 protein expression in formalin-fixed, paraffin-embedded (FFPE) neoplastic tissues.
  • Availability of a FFPE tumor tissue sample. FFPE sample can be from an archival tumor tissue sample. It should be from the most recent tumor tissue obtained and must not be >3 years old. If an archival sample is not available, the patient must be biopsied for CLDN6 staining. If an archival tumor sample is ≤3 years old but the patient has received a treatment that may influence expression of CLDN6 after the archival tumor sample was obtained, a fresh tumor biopsy is required.
  • Must have histological documentation of the original primary tumor via a pathology report.
  • Must have measurable disease per RECIST v1.1 (except for germ cell tumors, where patients can be evaluated according to Cancer-Antigen (CA)-125, Alpha-fetoprotein or beta-human chorionic gonadotropin (βhCG) [as applicable], or ovarian cancer, where patients can be evaluated according to CA-125. The pre-treatment sample must be at least twice the upper limit of normal).
  • Must have a histologically confirmed solid tumor that is metastatic or unresectable and for which there is no available standard therapy likely to confer clinical benefit, or the patient is not a candidate for such available therapy.
  • Must be ≥ 18 years of age at the time the pre-screening informed consent is signed.
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  • Must sign an informed consent form indicating that he or she understands the purpose of and procedures required for the trial and are willing to participate in the trial prior to any trial-related assessments or procedures.
  • Must have an Eastern Cooperative Oncology Group performance status of 0 to 1.
  • Must have adequate coagulation function at screening as defined in the protocol.
  • Must have adequate hematologic function at screening as defined in the protocol.
  • Must have adequate hepatic function at screening as defined in the protocol.
  • Must have adequate renal function at screening as defined in the protocol.
  • Must be able to attend trial visits as required by the protocol.
  • Women of childbearing potential (WOCBP) must have a negative serum (βhCG) test/value at screening. Patients who are post-menopausal or permanently sterilized can be considered as not having reproductive potential.
  • WOCBP must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the entire trial and thereafter.
  • WOCBP and men who are sexually active with a WOCBP and have not had a vasectomy must agree to use highly effective birth control method(s), as defined in the protocol. True abstinence is an acceptable alternative to the use of contraception.
  • Men must agree not to father a child or donate sperm, and WOCBP must agree not to become pregnant during the trial and for at least 12 months after the CLDN6 CAR-T infusion or CLDN6 RNA-LPX treatment.
  • For Part 2 only:
  • Histologically or cytologically confirmed solid tumor fulfilling inclusion criteria 1-4 that is metastatic or unresectable, and for whom there is no available standard therapy likely to confer clinical benefit, or patient who is not a candidate for such available therapy.

Who cannot join

  • Has received prior CAR-T therapy, except CLDN6 CAR-T therapy.
  • Has received vaccination with live virus vaccines within 6 weeks prior to the start of lymphodepletion (LD).
  • Receives concurrent systemic (oral or i.v.) steroid therapy >10 mg prednisolone daily, or its equivalent, for an underlying condition.
  • Has side effects of any prior therapy or procedures for any medical condition not recovered to National Cancer Institute Common Terminology Criteria for Adverse Avents version 5.0 Grade ≤1.
  • Medical conditions:
  • Current evidence of new or growing brain or spinal metastases during screening. Patients with known brain or spinal metastases may be eligible if they:
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  • Have had radiotherapy or another appropriate therapy for the brain or spinal metastases. The therapy must be completed at least 3 weeks prior to CLDN6 CAR-T administration,
  • Have no neurological symptoms,
  • Have stable brain or spinal disease on the computer tomography or magnetic resonance imaging scan within 3 weeks before CLDN6 CAR-T administration,
  • Are not undergoing acute corticosteroid therapy or steroid taper. Chronic steroid therapy is acceptable provided that the dose is stable for the last 14 days prior to screening (≤10 mg prednisolone daily or equivalent),
  • Do not require steroid therapy within 7 days before the first dose of CLDN6 CAR-T, and
  • Do not have anticipated imminent fracture or cord compression due to spinal bone metastases.
  • Has history of epilepsy. Isolated seizures in the past or febrile seizures in childhood are permitted; has a history of a cerebrovascular accident or transient ischemic attack less than 6 months ago.
  • Pericardial effusion requiring any drainage is excluded.
  • Has an active autoimmune disease including but not limited to inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or multiple sclerosis. Has any active immunologic disorder requiring immunosuppression with steroids or other immunosuppressive agents with the exception of patients with isolated vitiligo, resolved childhood asthma or atopic dermatitis, controlled hypoadrenalism or hypopituitarism, and euthyroid patients with a history of Grave's disease. Patients with controlled hyperthyroidism must be negative for thyroglobulin, thyroid peroxidase antibodies, and thyroid-stimulating immunoglobulin prior to trial drug administration.
  • Seropositivity for human immunodeficiency virus.
  • Known history/positive serology for hepatitis B requiring active antiviral therapy (unless immune due to vaccination or resolved natural infection or unless passive immunization due to immunoglobulin therapy). Patients with positive serology must have hepatitis B virus viral load below the limit of quantification.
  • Active hepatitis C virus (HCV) infection; patients who have completed curative antiviral treatment with HCV viral load below the limit of quantification are allowed.
  • Has a known hypersensitivity to a component of CLDN6 CAR-T or the CLDN6 RNA-LPX drug product, or another similar compound.
  • History of severe immediate hypersensitivity reaction to LD chemotherapy consisting of cyclophosphamide or fludarabine.
  • Has a history of another primary cancer within the 2 years prior to enrollment except for the following: Non-melanoma skin cancer, cervical carcinoma in situ, superficial bladder cancer, prostate cancer with currently undetectable prostate specific antigen, or other non-metastatic carcinoma that has been in complete remission without treatment for more than 2 years.
  • Receipt of allogenic stem cell transplantation in the 5 years prior to enrollment into the trial.
  • Patients with acute or chronic graft versus host disease.
  • Other comorbidities:
  • Has abnormal electrocardiograms that are clinically significant, such as QT prolongation.
  • In the opinion of the investigator, has any concurrent conditions that could pose an undue medical hazard or interfere with the interpretation of the trial results; these conditions include, but are not limited to:
  • Ongoing or active infection requiring antibiotic/antiviral/antifungal therapy
  • Concurrent congestive heart failure (New York Heart Association Functional Classification Class III or IV)
  • Concurrent unstable angina
  • Concurrent cardiac arrhythmia requiring treatment
  • Acute coronary syndrome within the previous 6 months
  • Significant pulmonary disease (shortness of breath at rest or on mild exertion) for example due concurrent severe obstructive pulmonary disease.
  • Has a cognitive, psychological or psychosocial impediment that would impair the ability of the patient to receive therapy according to the protocol or adversely affect the ability of the patient to comply with the informed consent process, protocol, or protocol-required visits and procedures.
  • Is pregnant or breastfeeding.
  • Disease-specific exclusion criteria:
  • Have a pure βhCG-secreting germ cell tumor.

Trial locations and contacts

12 sites in 4 countries.

12 sites in 4 countries

Germany8 sites

  • Charité - Universitätsmedizin Berlin - Campus Benjamin Franklin

    Berlin, 12200

  • Universitätsklinikum Köln AÖR-Centrum für Integrierte Onkologie (CIO)-Studienzentrum der Klinik I für Innere Medizin (CTU Cologne)

    Cologne, 50937

  • Universitätsklinikum Erlangen - Hämatologie & Intrinsische Onkologie - Medizinische Klinik 5

    Erlangen, 91054

  • Universitätsklinikum Hamburg Eppendorf - II Medizinische Klinik und Poliklinik

    Hamburg, 20246

  • Medizinische Hochschule Hannover - Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation

    Hanover, 30625

  • Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg

    Heidelberg, 69120

  • Universitätsmedizin Mainz - III Medizinische Klinik und Poliklinik

    Mainz, 55131

  • Universitätsklinikum Regensburg - Klinik und Poliklinik für Innere Medizin III

    Regensburg, 93053

Other trials in Germany

Netherlands2 sites

  • He Nederlands Kanker Instituut (The Netherlands Cancer Institute) - Antoni van Leeuwenhoek Ziekenhuis (NKI-AVL)

    Amsterdam, 1066

  • Erasmus MC - Universitair Medisch Centrum - Medical oncology

    Rotterdam, 3015

Other trials in Netherlands

Australia1 site

  • Peter MacCallum Cancer Centre

    Melbourne, Victoria, 3000

Other trials in Australia

Sweden1 site

  • Karolinska Comprehensive Cancer Center Cancerstudieenheten Huddinge Karolinska Universitetssjukhuset

    Stockholm, 14186

Other trials in Sweden

About this study

Official title: Phase I/IIa, First-in-human, Open-label, Dose Escalation Trial With Expansion Cohorts to Evaluate Safety and Preliminary Efficacy of CLDN6 CAR-T With or Without CLDN6 RNA-LPX in Patients With CLDN6-positive Relapsed or Refractory Advanced Solid Tumors

This is a Phase I, FIH, open-label, multi-site, dose escalation trial with expansion cohorts to evaluate safety and preliminary efficacy of claudin 6 (CLDN6) chimeric antigen receptor T cells (CAR-T) with or without CLDN6 ribonucleic acid lipoplexes (RNA-LPX) in patients with CLDN6-positive relapsed or refractory advanced solid tumors.

Read the detailed description

CLDN6 CAR-T is used as a general term to refer to CLDN6 CAR-T cells from the manual and automated manufacturing processes.

The trial consists of two parts.

The trial began using a manual CLDN6 CAR-T production process.

Part 1 is a CLDN6 CAR-T dose escalation in lymphodepleted patients until the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of CLDN6 CAR-T are defined.

Dose escalation with CLDN6 CAR-T cells from the automated manufacturing process follows an accelerated titration design, as opposed to the classical 3+3 trial design used for the dose escalation with CLDN6 CAR-T manufactured with the manual process.

In addition, an optional de-escalation dose level may be explored to further evaluate clinical safety and efficacy of CLDN6 CAR-T manufactured with the automated process.

Part 2 is a vaccine-modulated dose escalation using a bifurcated design until the MTD and/or RP2D of CLDN6 CAR-T + CLDN6 RNA-LPX are defined.

The trial started with a CLDN6 encoding uridine containing RNA formulated in lipoplexes (CLDN6 uRNA-LPX). In order to optimize CAR-T cell persistence in patients, an alternative RNA-LPX, CLDN6 modRNA-LPX, will be tested once the RP2D dose for CLDN6 CAR-T ± CLDN6 RNA-LPX is identified.

The planned trial duration per patient in the main trial is 25 months. Patients exposed to genetically engineered therapies may be at risk of delayed adverse events. Therefore, after patients complete or prematurely discontinue participation in the main trial, they will be asked to participate in a long-term follow-up (LTFU) period to assess long-term safety and efficacy for up to 15 years. Patients will be asked to re-consent to participate in this LTFU period.

Conditions
Solid Tumor
Being tested
CLDN6 CAR-T, CLDN6 uRNA-LPX/CLDN6 modRNA-LPX
Keywords
CLDN6-positive relapsed or refractory advanced solid tumors, Testicular cancer, Ovarian cancer, Gastric cancer, Endometrial cancer, Non-small cell lung cancer (NSCLC)
Medical subject headings
Testicular Neoplasms, Ovarian Neoplasms, Stomach Neoplasms, Endometrial Neoplasms, Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CLDN6 CAR-TBiological

    administered as an intravenous (i.v.) infusion.

  • CLDN6 uRNA-LPX/CLDN6 modRNA-LPXBiological

    administered as an i.v. injection at protocol-specified intervals.

Study groups in NCT04503278
Study groupRoleWhat they receive
Part 1 - CLDN6 CAR-TExperimentalDose escalation in lymphodepleted patients until the MTD and/or RP2D.
Receives: Biological: CLDN6 CAR-T
Part 2 Vaccine-modulated - CLDN6 uRNA-LPX/CLDN6 modRNA-LPXExperimentalDose escalation until the MTD and/or RP2D.
Receives: Biological: CLDN6 CAR-T; Biological: CLDN6 uRNA-LPX/CLDN6 modRNA-LPX

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Occurrence of treatment-emergent adverse events (TEAEs) including ≥ Grade 3, serious, fatal TEAEs by relationship

    Measured: up to 25 months

  2. Occurrence of dose reduction and discontinuation of investigational medicinal product (IMP) due to TEAEs

    Measured: up to 25 months

  3. Occurrence of dose-limiting toxicity (DLT) during the DLT evaluation period

    Measured: Day 1 to day 28

Secondary outcomes (4)

  1. Change from baseline in the levels and kinetics of soluble immune factors measured by cytokine multiplex assay

    Systemic effects in patients will be assessed (e.g., tumor necrosis factor, interferon (IFN)-γ, interleukin (IL)-2, IL-10, soluble IL-2Rα, interferon-gamma-induced- protein (IP)-10, IL-12, IFN-α, IL-6, soluble IL-6R).

    Measured: Baseline up to 25 months

  2. Objective response rate

    Defined as the proportion of patients in whom a complete response (CR) or partial response (PR) (per response evaluation criteria in solid tumors version 1.1 [RECIST v1.1] or defined by tumor marker change from baseline when RECIST evaluation is not feasible) is observed as best overall response

    Measured: up to 25 months

  3. Disease control rate

    Defined as the proportion of patients in whom a CR or PR or stable disease (SD) per RECIST v1.1 or defined by tumor marker change from baseline when RECIST evaluation is not feasible (SD assessed at least 6 weeks after the first dose) is observed as best overall response

    Measured: up to 25 months

  4. Duration of response

    Defined as the time from first objective response (CR or PR per RECIST v1.1 or first response defined by tumor marker change from baseline when RECIST evaluation is not feasible) to first occurrence of objective progressive disease (PD) or death from any cause, whichever occurs first

    Measured: up to 25 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Aug 2020
  2. Study start16 Sep 2020
  3. Primary completionAug 2028 (estimated)
  4. Study completionAug 2041 (estimated)

Resources

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
Non-randomised
Intervention model
Factorial
Masking
None (open label)
Enrolment
214 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04503278
Sponsor's protocol ID
BNT211-01
Other IDs
2019-004323-20, 2024-514962-38-00, 2019
Status last verified
Jun 2026
First submitted
28 Jul 2020
Last updated
18 Jun 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Mackensen A, Haanen JBAG, Koenecke C, Alsdorf W, Wagner-Drouet E, Borchmann P, Heudobler D, Ferstl B, Klobuch S, Bokemeyer C, Desuki A, Luke F, Kutsch N, Muller F, Smit E, Hillemanns P, Karagiannis P, Wiegert E, He Y, Ho T, Kang-Fortner Q, Schlitter AM, Schulz-Eying C, Finlayson A, Flemmig C, Kuhlcke K, Preussner L, Rengstl B, Tureci O, Sahin U. CLDN6-specific CAR-T cells plus amplifying RNA vaccine in relapsed or refractory solid tumors: the phase 1 BNT211-01 trial. Nat Med. 2023 Nov;29(11):2844-2853. doi: 10.1038/s41591-023-02612-0. Epub 2023 Oct 23.

    PubMed 37872225

  • Simon AG, Lyu SI, Laible M, Woll S, Tureci O, Sahin U, Alakus H, Fahrig L, Zander T, Buettner R, Bruns CJ, Schroeder W, Gebauer F, Quaas A. The tight junction protein claudin 6 is a potential target for patient-individualized treatment in esophageal and gastric adenocarcinoma and is associated with poor prognosis. J Transl Med. 2023 Aug 17;21(1):552. doi: 10.1186/s12967-023-04433-8.

    PubMed 37592303

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CLDN6 CAR-T and CLDN6 uRNA-LPX/CLDN6 modRNA-LPX in people with Solid Tumor, run by BioNTech Cell & Gene Therapies GmbH at 12 sites in 4 countries.

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 19 inclusion and 36 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: under way, not looking for participants, as of the sponsor's last update on 18 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in Germany, Netherlands, Australia, Sweden. 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?

This study is still under way. Results are not available in the source record yet.

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?

Occurrence of treatment-emergent adverse events (TEAEs) including ≥ Grade 3, serious, fatal TEAEs by relationship (time frame: up to 25 months). The study lists 3 primary outcomes in all. 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 NCT04503278, which also lists 2 linked publications.

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 18 Jun 2026.

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