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 1/2

Recruiting

• Conditions: Solid Tumors

• Registration Number: 2024-514962-38-00
• Lead Sponsor: BioNTech Cell & Gene Therapies GmbH, BioNTech Cell & Gene Therapies GmbH

Brief Summary

To assess the safety and tolerability of claudin 6 (CLDN6) Chimeric antigen receptor T cell (CAR-T) ± CLDN6 Liposomally-formulated vaccine encoding ribonucleic acid (RNA-LPX) and to assess the comparability of CLDN6 CAR-T from the manual and automated processes

Detailed Description

Not available

Study Timeline

• Study First Posted: 2024-07-01
• Last Update Posted: 2024-07-04

Recruitment & Eligibility

• Status: Ongoing, recruiting
• Sex: Not specified
• Target Recruitment: 145

Inclusion Criteria

Each patient enrolled in the trial must have CLDN6-positive tumor regardless of tumor histology defined as ≥ 50% of tumor cells expressing ≥ 2+ CLDN6 protein using a semi-quantitative immunohistochemistry (IHC) assay in a central laboratory for specific detection of CLDN6 protein expression in formalin-fixed, paraffin-embedded (FFPE) neoplastic tissues.

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 (beta-human chorionic gonadotropin) 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 that 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.

Availability of a FFPE tumor tissue sample. FFPE can be from an archival tumor tissue sample, and it should be from the most recent tumor tissue obtained. If this is not available, patient must be biopsied for CLDN6 staining.

Must have histological documentation of the original primary tumor via a pathology report.

Must have measurable disease per RECIST 1.1 (except for germ cell tumors, where patients can be evaluated according to Cancer-Antigen (CA)-125, Alpha-fetoprotein or human chorionic gonadotropin [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 patient who 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 (ICF) 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.

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 events (CTCAE v.5) Grade ≤ 1.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Occurrence of treatment-emergent adverse events (TEAEs) including ≥ Grade 3, serious, fatal TEAEs by relationship		Occurrence of treatment-emergent adverse events (TEAEs) including ≥ Grade 3, serious, fatal TEAEs by relationship
Occurrence of dose reduction and discontinuation of investigational medicinal product (IMP) due to TEAEs		Occurrence of dose reduction and discontinuation of investigational medicinal product (IMP) due to TEAEs
Occurrence of dose-limiting toxicity (DLT) during the DLT evaluation period		Occurrence of dose-limiting toxicity (DLT) during the DLT evaluation period

Secondary Outcome Measures

Name	Time	Method
Change from baseline in the levels and kinetics of soluble immune factors measured by cytokine multiplex assay		Change from baseline in the levels and kinetics of soluble immune factors measured by cytokine multiplex assay
Objective response rate (ORR) defined as the proportion of patients in whom a complete response (CR) or partial response (PR) (per response evaluation criteria in solid tumors [RECIST 1.1]) is observed as best overall response		Objective response rate (ORR) defined as the proportion of patients in whom a complete response (CR) or partial response (PR) (per response evaluation criteria in solid tumors [RECIST 1.1]) is observed as best overall response
Duration of response (DOR) defined as the time from first objective response (CR or PR per RECIST 1.1) to first occurrence of objective progressive disease (PD) per RECIST 1.1/recurrence or death from any cause, whichever occurs first		Duration of response (DOR) defined as the time from first objective response (CR or PR per RECIST 1.1) to first occurrence of objective progressive disease (PD) per RECIST 1.1/recurrence or death from any cause, whichever occurs first

Trial Locations

Locations (11)

Charite Universitaetsmedizin Berlin KöR; 🇩🇪 Berlin, Germany

Medizinische Hochschule Hannover; 🇩🇪 Hanover, Germany

Universitaetsklinikum Regensburg AöR; 🇩🇪 Regensburg, Germany

National Center For Tumor Diseases (NCT) Heidelberg; 🇩🇪 Heidelberg, Germany

University Medical Center Hamburg-Eppendorf; 🇩🇪 Hamburg, Germany

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR; 🇩🇪 Mainz, Germany

University Hospital Cologne AöR; 🇩🇪 Cologne, Germany

Universitaetsklinikum Erlangen AöR; 🇩🇪 Erlangen, Germany

Region Stockholm – SLSO; 🇸🇪 Stockholm, Sweden

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC); 🇳🇱 Rotterdam, Netherlands

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Charite Universitaetsmedizin Berlin KöR

🇩🇪Berlin, Germany

Antonia Busse

Site contact

+4930450513514

antonia.busse@charite.de