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 | Recruiting Phase 1

• 3 other identifiers: BNT211-012019-004323-202024-514962-38-00
• Study Type: interventional
• Target: 214
• Locations: 4 countries
• Sites: 12

Brief 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 advanced solid tumors.

Conditions

Solid Tumor

Keywords

CLDN6-positive relapsed or refractory advanced solid tumors; Testicular cancer; Ovarian cancer; Gastric cancer; Endometrial cancer; Non-small cell lung cancer (NSCLC)

Outcome Measures

Primary Outcomes (3)

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

  up to 25 months

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

  up to 25 months

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

  Day 1 to day 28

Secondary Outcomes (4)

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

  Baseline up to 25 months

• Objective response rate

  up to 25 months

• Disease control rate

  up to 25 months

• Duration of response

  up to 25 months

Study Arms (2)

Part 1 - CLDN6 CAR-T

EXPERIMENTAL

Dose escalation in lymphodepleted patients until the MTD and/or RP2D.

Biological: CLDN6 CAR-T

Part 2 Vaccine-modulated - CLDN6 uRNA-LPX/CLDN6 modRNA-LPX

EXPERIMENTAL

Dose escalation until the MTD and/or RP2D.

Biological: CLDN6 CAR-T; Biological: CLDN6 uRNA-LPX/CLDN6 modRNA-LPX

Interventions

CLDN6 CAR-T BIOLOGICAL

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

Part 1 - CLDN6 CAR-T; Part 2 Vaccine-modulated - CLDN6 uRNA-LPX/CLDN6 modRNA-LPX

CLDN6 uRNA-LPX/CLDN6 modRNA-LPX BIOLOGICAL

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

Part 2 Vaccine-modulated - CLDN6 uRNA-LPX/CLDN6 modRNA-LPX

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• 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.

Sponsors & Collaborators

• BioNTech Cell & Gene Therapies GmbH: lead

Study Sites (12)

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

COMPLETED

Charité - Universitätsmedizin Berlin - Campus Benjamin Franklin

Berlin, 12200, Germany

RECRUITING

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

Cologne, 50937, Germany

RECRUITING

Universitätsklinikum Erlangen - Hämatologie & Intrinsische Onkologie - Medizinische Klinik 5

Erlangen, 91054, Germany

RECRUITING

Universitätsklinikum Hamburg Eppendorf - II Medizinische Klinik und Poliklinik

Hamburg, 20246, Germany

RECRUITING

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

Hanover, 30625, Germany

RECRUITING

Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg

Heidelberg, 69120, Germany

RECRUITING

Universitätsmedizin Mainz - III Medizinische Klinik und Poliklinik

Mainz, 55131, Germany

RECRUITING

Universitätsklinikum Regensburg - Klinik und Poliklinik für Innere Medizin III

Regensburg, 93053, Germany

RECRUITING

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

Amsterdam, 1066, Netherlands

RECRUITING

Erasmus MC - Universitair Medisch Centrum - Medical oncology

Rotterdam, 3015, Netherlands

RECRUITING

Karolinska Comprehensive Cancer Center Cancerstudieenheten Huddinge Karolinska Universitetssjukhuset

Stockholm, 14186, Sweden

RECRUITING

Related Publications (2)

• 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.

  PMID: 37872225 DERIVED

• 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.

  PMID: 37592303 DERIVED

MeSH Terms

Conditions

Testicular Neoplasms; Ovarian Neoplasms; Stomach Neoplasms; Endometrial Neoplasms; Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases; Endocrine System Diseases; Testicular Diseases; Gonadal Disorders; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Neoplasms, Female; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Uterine Neoplasms; Uterine Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• BioNTech Responsible Person

  BioNTech SE

  STUDY DIRECTOR

Central Study Contacts

BioNTech clinical trials patient information

CONTACT

+49 6131 9084; patients@biontech.de

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2020
• First Posted: August 7, 2020
• Study Start: September 16, 2020
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2041
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

NL (2); SE (1); DE (8); AU (1)