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Updated May 2026 · ClinicalTrials.gov

RECRUITINGPhase 1INTERVENTIONAL

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

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

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 (NCT04503278) is a Phase 1 interventional studying Solid Tumor, sponsored by BioNTech Cell & Gene Therapies GmbH. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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.

What Stage of Research Is This?

Phase 1 trials test a new treatment for the first time in humans, focusing on safety, dosing, and how the body processes the drug. For Solid Tumor, a Phase 1 study typically enrolls a small number of participants — often healthy volunteers or patients who have exhausted standard treatment options. Phase 1 results determine whether a treatment moves into larger Phase 2 efficacy studies.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 214 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Solid Tumor subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Who May Qualify: - 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 tumors that can be measured on scans 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 diagnosed by tissue sample (biopsy-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 willing to sign a consent form is signed. - Must sign an willing to sign a consent form 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. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: * 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. * 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. Exclusion Criteria: * 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: 1. 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, 2. Have no neurological symptoms, 3. Have stable brain or spinal disease on the computer tomography or magnetic resonance imaging scan within 3 weeks before CLDN6 CAR-T administration, 4. 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), 5. Do not require steroid therapy within 7 days before the first dose of CLDN6 CAR-T, and 6. 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: 1. Ongoing or active infection requiring antibiotic/antiviral/antifungal therapy 2. Concurrent congestive heart failure (New York Heart Association Functional Classification Class III or IV) 3. Concurrent unstable angina 4. Concurrent cardiac arrhythmia requiring treatment 5. Acute coronary syndrome within the previous 6 months 6. 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.

Treatments Being Tested

BIOLOGICAL

CLDN6 CAR-T

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

BIOLOGICAL

CLDN6 uRNA-LPX/CLDN6 modRNA-LPX

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

Locations (12)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Peter MacCallum Cancer Centre
Melbourne, Victoria, Australia
Charité - Universitätsmedizin Berlin - Campus Benjamin Franklin
Berlin, Germany
Universitätsklinikum Köln AÖR-Centrum für Integrierte Onkologie (CIO)-Studienzentrum der Klinik I für Innere Medizin (CTU Cologne)
Cologne, Germany
Universitätsklinikum Erlangen - Hämatologie & Intrinsische Onkologie - Medizinische Klinik 5
Erlangen, Germany
Universitätsklinikum Hamburg Eppendorf - II Medizinische Klinik und Poliklinik
Hamburg, Germany
Medizinische Hochschule Hannover - Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation
Hanover, Germany
Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg
Heidelberg, Germany
Universitätsmedizin Mainz - III Medizinische Klinik und Poliklinik
Mainz, Germany
Universitätsklinikum Regensburg - Klinik und Poliklinik für Innere Medizin III
Regensburg, Germany
He Nederlands Kanker Instituut (The Netherlands Cancer Institute) - Antoni van Leeuwenhoek Ziekenhuis (NKI-AVL)
Amsterdam, Netherlands
Erasmus MC - Universitair Medisch Centrum - Medical oncology
Rotterdam, Netherlands
Karolinska Comprehensive Cancer Center Cancerstudieenheten Huddinge Karolinska Universitetssjukhuset
Stockholm, Sweden

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT04503278), the sponsor (BioNTech Cell & Gene Therapies GmbH), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT04503278 clinical trial studying?

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. The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT04503278?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT04503278?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT04503278. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT04503278. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.