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JOURNAL ONKOLOGIE – STUDIE

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

Rekrutierend

NCT-Nummer:
NCT04503278

Studienbeginn:
September 2020

Letztes Update:
25.11.2020

Wirkstoff:
CLDN6 CAR-T, CLDN6 RNA-LPX

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
BioNTech Cell & Gene Therapies GmbH

Collaborator:
-

Studienleiter

BioNTech Responsible Person
Study Director
BioNTech SE

Kontakt

BioNTech clinical trials patient information
Kontakt:
Phone: +49 6131 9084
Phone (ext.): 1919
E-Mail: patients@biontech.de
» Kontaktdaten anzeigen

Studienlocations (3 von 3)

Universitätsklinikum Erlangen - Hämatologie & Intrinsische Onkologie - Medizinische Klinik 5
91054 Erlangen
(Bayern)
GermanyRekrutierend» Google-Maps
Medizinische Hochschule Hannover - Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation
30625 Hannover
(Niedersachsen)
GermanyRekrutierend» Google-Maps
He Nederlands Kanker Instituut (The Netherlands Cancer Institute) - Antoni van Leeuwenhoek Ziekenhuis (NKI-AVL)
1066 Amsterdam
NetherlandsRekrutierend» Google-Maps

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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.

Studien-Rationale

Primary outcome:

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:

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)

Studien-Arme

  • Experimental: Part 1 CLDN6 CAR-T
    Dose escalation in lymphodepleted patients until the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D).
  • Experimental: Part 2 Vaccine-modulated
    Dose escalation until the MTD and/or RP2D.

Geprüfte Regime

  • CLDN6 CAR-T:
    administered as an i.v. infusion.
  • CLDN6 RNA-LPX:
    administered as an i.v. injection at protocol-specified intervals.

Quelle: ClinicalTrials.gov


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