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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04503278




Registration number
NCT04503278
Ethics application status
Date submitted
28/07/2020
Date registered
7/08/2020
Date last updated
31/05/2024

Titles & IDs
Public title
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
Scientific 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 With or Without CLDN6 RNA-LPX in Patients With CLDN6-positive Relapsed or Refractory Advanced Solid Tumors
Secondary ID [1] 0 0
2019-004323-20
Secondary ID [2] 0 0
BNT211-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumor 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - CLDN6 CAR-T
Other interventions - CLDN6 uRNA-LPX/CLDN6 modRNA-LPX

Experimental: Part 1 - CLDN6 CAR-T - Dose escalation in lymphodepleted patients until the MTD and/or RP2D.

Experimental: Part 2 Vaccine-modulated - CLDN6 uRNA-LPX/CLDN6 modRNA-LPX - Dose escalation until the MTD and/or RP2D.


Other interventions: CLDN6 CAR-T
administered as an intravenous (i.v.) infusion.

Other interventions: CLDN6 uRNA-LPX/CLDN6 modRNA-LPX
administered as an i.v. injection at protocol-specified intervals.
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Occurrence of treatment-emergent adverse events (TEAEs) including = Grade 3, serious, fatal TEAEs by relationship
Timepoint [1] 0 0
up to 25 months
Primary outcome [2] 0 0
Occurrence of dose reduction and discontinuation of investigational medicinal product (IMP) due to TEAEs
Timepoint [2] 0 0
up to 25 months
Primary outcome [3] 0 0
Occurrence of dose-limiting toxicity (DLT) during the DLT evaluation period
Timepoint [3] 0 0
Day 1 to day 28
Secondary outcome [1] 0 0
Change from baseline in the levels and kinetics of soluble immune factors measured by cytokine multiplex assay
Timepoint [1] 0 0
Baseline up to 25 months
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
up to 25 months
Secondary outcome [3] 0 0
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
Timepoint [3] 0 0
up to 25 months
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
up to 25 months

Eligibility
Key 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.

- 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.

- 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

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,

2. Have no neurological symptoms,

3. Have stable brain or spinal disease on the computer tomography or magnetic
resonance imaging scan within 4 weeks before signing of the ICF,

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,

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 CLDN6 RNA-LPX cancer
vaccine drug product, or another similar compound.

- Only for patients recruited for Part 2 with LD chemotherapy (CLDN6 CAR-T + CLDN6
RNA-LPX with LD chemotherapy): 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 (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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Factorial
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
16/09/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/01/2040
Actual
Sample size
Target
145
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
Germany
State/province [1] 0 0
Berlin
Country [2] 0 0
Germany
State/province [2] 0 0
Erlangen
Country [3] 0 0
Germany
State/province [3] 0 0
Hamburg
Country [4] 0 0
Germany
State/province [4] 0 0
Hannover
Country [5] 0 0
Germany
State/province [5] 0 0
Heidelberg
Country [6] 0 0
Germany
State/province [6] 0 0
Köln
Country [7] 0 0
Germany
State/province [7] 0 0
Mainz
Country [8] 0 0
Germany
State/province [8] 0 0
Regensburg
Country [9] 0 0
Netherlands
State/province [9] 0 0
Amsterdam
Country [10] 0 0
Netherlands
State/province [10] 0 0
Rotterdam
Country [11] 0 0
Sweden
State/province [11] 0 0
Stockholm

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
BioNTech Cell & Gene Therapies GmbH
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase I, FIH, open-label, multicenter, 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04503278
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
BioNTech Responsible Person
Address 0 0
BioNTech SE
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
BioNTech clinical trials patient information
Address 0 0
Country 0 0
Phone 0 0
+49 6131 9084
Fax 0 0
Email 0 0
patients@biontech.de
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04503278