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A Trial to Evaluate the Safety and Efficacy of CLDN6 CAR-T +/- CLDN6 RNA-LPX

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04503278
Recruitment Status : Recruiting
First Posted : August 7, 2020
Last Update Posted : October 14, 2020
Information provided by (Responsible Party):
BioNTech SE ( BioNTech Cell & Gene Therapies GmbH )

Brief Summary:
This is a Phase I/IIa, FIH, open-label, multicenter, dose escalation trial with expansion cohorts to evaluate safety and preliminary efficacy of CLDN6 CAR-T +/- CLDN6 RNA-LPX in patients with CLDN6-positive relapsed or refractory advanced solid tumors.

Condition or disease Intervention/treatment Phase
Solid Tumor Biological: CLDN6 CAR-T Biological: CLDN6 RNA-LPX Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/IIa, First-in-human (FIH), Open-label, Dose Escalation Trial With Expansion Cohorts to Evaluate Safety and Preliminary Efficacy of CLDN6 CAR-T +/- CLDN6 RNA-LPX in Patients With CLDN6-positive Relapsed or Refractory Advanced Solid Tumors
Actual Study Start Date : September 16, 2020
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : September 2036

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Part 1 CLDN6 CAR-T
Dose escalation in lymphodepleted patients until the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D).
Biological: CLDN6 CAR-T
administered as an i.v. infusion.

Experimental: Part 2 Vaccine-modulated
Dose escalation until the MTD and/or RP2D.
Biological: CLDN6 CAR-T
administered as an i.v. infusion.

Biological: CLDN6 RNA-LPX
administered as an i.v. injection at protocol-specified intervals.

Primary Outcome Measures :
  1. Occurrence of treatment-emergent adverse events (TEAEs) within a patient including ≥ Grade 3, serious, fatal TEAEs by relationship [ Time Frame: up to 25 months ]
  2. Occurrence of dose reduction and discontinuation of investigational medicinal product (IMP) within a patient due to TEAEs [ Time Frame: up to 25 months ]
  3. Occurrence of dose-limiting toxicity (DLT) within a patient during the DLT evaluation period [ Time Frame: Day 1 to day 28 ]

Secondary Outcome Measures :
  1. Change from baseline in the levels of soluble immune factors [ Time Frame: Baseline up to 25 months ]
    Systemic effects in patients will be assessed (e.g., TNF, IFN-γ, IL-2, soluble IL-2Rα, IP-10, IL-12, IFN-α, IL-6, soluble IL-6R).

  2. 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 [ Time Frame: up to 25 months ]
  3. Disease control rate (DCR) defined as the proportion of patients in whom a CR or PR or stable disease (SD) (per RECIST 1.1, SD assessed at least 6 weeks after the first dose) is observed as best overall response [ Time Frame: up to 25 months ]
  4. Duration of response (DOR) defined as the time from first objective response (CR or PR per RECIST 1.1) to first occurrence of objective tumor progression (Progressive disease (PD) per RECIST 1.1) or death from any cause, whichever occurs first [ Time Frame: up to 25 months ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria: Phase 1 of the trial

  • Each patient enrolled in the trial must have CLDN6-positive tumor regardless of tumor histology defined as ≥ 50% of tumors 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.
  • 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.
  • Must have a histologically confirmed solid tumor 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.
  • Must be ≥ 18 years of age at the time the pre-screening informed consent is signed.
  • 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 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.
  • A man who is sexually active with a WOCBP and has not had a vasectomy must agree to use a barrier method of birth control.
  • All men must also not donate sperm 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 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: Phase 1 of the trial

  • Has received prior CAR-T cell 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 (NCI) common terminology criteria for adverse events (CTCAE v.5) 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. Had radiotherapy or another appropriate therapy for the brain or spinal metastases,
    2. Have no neurological symptoms,
    3. Have stable brain or spinal disease on the computer tomography (CT) or magnetic resonance imaging (MRI) scan within 4 weeks before signing of the Informed consent form,
    4. Must not be undergoing acute corticosteroid therapy or steroid taper. Chronic steroid therapy is acceptable provided that the dose is stable for the last 14 d prior to screening (≤ 10 mg prednisolone daily or equivalent),
    5. Do not require steroid therapy within 7 d before the first dose of CLDN6 CAR-T,
    6. Spinal bone metastases are allowed, unless imminent fracture or cord compression is anticipated.
  • Has history of seizures other than isolated febrile seizure in childhood; has a history of a cerebrovascular accident or transient ischemic attack less than 6 months ago.
  • Pericardial effusion requiring any drainage is excluded.
  • Has a history of autoimmune disease active or past 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 (HIV).
  • 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 CLDN6 RNA-LPX cancer vaccine 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 (ECGs) 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 (excluding asymptomatic atrial fibrillation)
    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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04503278

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Contact: BioNTech clinical trials patient information +49 6131 9084 ext 1919
Contact: BioNTech clinical trial information desk +49 6131 9084 ext 0

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He Nederlands Kanker Instituut (The Netherlands Cancer Institute) - Antoni van Leeuwenhoek Ziekenhuis (NKI-AVL) Recruiting
Amsterdam, Netherlands, 1066
Sponsors and Collaborators
BioNTech Cell & Gene Therapies GmbH
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Study Director: BioNTech Responsible Person BioNTech SE
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Responsible Party: BioNTech Cell & Gene Therapies GmbH Identifier: NCT04503278    
Other Study ID Numbers: BNT211-01
2019-004323-20 ( EudraCT Number )
First Posted: August 7, 2020    Key Record Dates
Last Update Posted: October 14, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No