Clinical trial • Phase I/II • Oncology

CLDN6 CAR-T for Solid tumors | Non-small cell lung cancer | Ovarian cancer | Uterine cancer | Gastric cancer | Testicular cancer | Carcinoma of unknown primary

Phase I/II trial of CLDN6 CAR-T for Solid tumors | Non-small cell lung cancer | Ovarian cancer | Uterine cancer | Gastric cancer | Testicular cancer | Car…

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Solid tumors | Non-small cell lung cancer | Ovarian cancer | Uterine cancer | Gastric cancer | Testicular cancer | Carcinoma of unknown primary
Trial Stage
Phase I/II
Drug Modality
Cell therapy | Other RNA

Key dates

Initial CTIS Submission Date
14-06-2024
First CTIS Authorization Date
01-07-2024

Trial design

open-label, none/not specified-controlled, adaptive Phase I/II trial across 11 sites in Netherlands, Sweden, Germany.

Open Label
Yes
Comparator
None/Not specified
Adaptive
True, dose-escalation design with expansion cohorts; MTD/RP2D to be identified based on occurrence of dose-limiting toxicities (DLT) with MTD defined as highest tolerated dose where <33% of patients experience a DLT.
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
206

Eligibility

Recruits 206 Vulnerable population selected; no specific description of vulnerable populations or consent/assent procedures is provided in the available trial record..

Vulnerable Population
Vulnerable population selected; no specific description of vulnerable populations or consent/assent procedures is provided in the available trial record.

Inclusion criteria

  • {"criterion_text":"- Must have a 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 (IHC) assay for specific detection of CLDN6 protein expression in formalin-fixed, paraffin-embedded neoplastic tissues.\n- Must have measurable disease per RECIST 1.1 (except for germ cell tumor where patients can be evaluated according to cancer antigen (CA)-125, AFP, or beta human chorionic gonadotropin [βhCG] [as applicable] or ovarian cancer patients where patients can be evaluated according to CA-125. The pre-treatment sample must be at least twice the upper limit of normal [ULN]).\n- 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 the patient is not a candidate for such available therapy."}

Exclusion criteria

  • {"criterion_text":"- Has received prior CAR-T therapy, except CLDN6 CAR-T therapy.\n- Has received vaccination with live virus vaccines within 6 weeks prior to the start of lymphodepletion (LD).\n- Receives concurrent systemic (oral or i.v.) steroid therapy > 10 mg prednisolone daily, or its equivalent, for an underlying condition.\n- Current evidence of new or growing brain or spinal metastases during screening.\n- 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."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Occurrence of treatment-emergent adverse events (TEAEs) including ≥ Grade 3, serious, fatal TEAEs by relationship\n- Occurrence of dose reduction and discontinuation of investigational medicinal product (IMP) due to TEAEs\n- Occurrence of dose-limiting toxicity (DLT) during the DLT evaluation period","definition_or_measurement_approach":""}

Secondary endpoints

  • {"endpoint_text":"- Change from baseline in the levels and kinetics of soluble immune factors measured by cytokine multiplex assay\n- Objective response rate (ORR) defined as the proportion of patients in whom a complete response (CR) or partial response (PR) (per RECIST 1.1 or defined by tumor marker change from baseline when RECIST evaluation is not feasible) is observed as best overall response\n- Disease control rate (DCR) defined as the proportion of patients in whom a CR or PR or stable disease (SD) per RECIST 1.1 or defined by tumor marker change from baseline when RECIST evaluation is not feasible (SD assessed at least 6 weeks after the first dose) is observed as best overall response\n- Duration of response (DOR) defined as the time from first objective response (CR or PR per RECIST 1.1 or first response defined by tumor marker change from baseline when RECIST evaluation is not feasible) to first occurrence of objective PD or death from any cause, whichever occurs first","definition_or_measurement_approach":"Change from baseline in soluble immune factors measured by cytokine multiplex assay; ORR defined as proportion with CR or PR per RECIST 1.1 or defined by tumor marker change when RECIST not feasible; DCR defined as proportion with CR, PR or SD per RECIST 1.1 (SD assessed ≥6 weeks after first dose) or tumor marker change when RECIST not feasible; DOR defined as time from first objective response to objective PD or death."}

Recruitment

Planned Sample Size
206
Recruitment Window Months
249
Consent Approach
Informed consent to be obtained using subject information and informed consent forms (multiple ICF documents listed: e.g., L1_SIS-ICF_Main_FP and other versions). The available record lists multiple ICF documents and versions but does not provide specific detail on assent, age-specific consent processes, or languages.

Geography

Total Number Of Sites
11
Total Number Of Participants
206

Netherlands

Earliest CTIS Part Ii Submission Date
06-06-2024
Latest Decision Or Authorization Date
11-11-2025
Processing Time Days
523
Number Of Sites
2
Number Of Participants
55

Sites

Site Name
Netherlands Cancer Institute
Department Name
Medical Oncology
Principal Investigator Name
John Haanen
Principal Investigator Email
j.haanen@nki.nl
Contact Person Name
John Haanen
Contact Person Email
j.haanen@nki.nl
Site Name
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Department Name
Medical Oncology
Principal Investigator Name
Sander Bins
Principal Investigator Email
s.bins@erasmusmc.nl
Contact Person Name
Sander Bins
Contact Person Email
s.bins@erasmusmc.nl

Sweden

Earliest CTIS Part Ii Submission Date
06-06-2024
Latest Decision Or Authorization Date
11-11-2025
Processing Time Days
523
Number Of Sites
1
Number Of Participants
10

Sites

Site Name
Region Stockholm – SLSO
Department Name
Centrum för allogen Stamcellstransplantation
Principal Investigator Name
Stephan Mielke
Principal Investigator Email
stephan.mielke@regionstockholm.se
Contact Person Name
Stephan Mielke

Germany

Earliest CTIS Part Ii Submission Date
06-06-2024
Latest Decision Or Authorization Date
13-11-2025
Processing Time Days
525
Number Of Sites
8
Number Of Participants
141

Sites

Site Name
Universitaetsklinikum Erlangen AöR
Department Name
Medizinische Klinik 5
Principal Investigator Name
Andreas Mackensen
Principal Investigator Email
med5-direktion@uk-erlangen.de
Contact Person Name
Andreas Mackensen
Contact Person Email
med5-direktion@uk-erlangen.de
Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Universitätsmedizin Berlin, Campus Benjamin Franklin
Principal Investigator Name
Antonia Busse
Principal Investigator Email
antonia.busse@charite.de
Contact Person Name
Antonia Busse
Contact Person Email
antonia.busse@charite.de
Site Name
University Hospital Cologne AöR
Principal Investigator Name
Nadine Kutsch
Principal Investigator Email
Nadine.kutsch@uk-koeln.de
Contact Person Name
Nadine Kutsch
Contact Person Email
Nadine.kutsch@uk-koeln.de
Site Name
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR
Principal Investigator Name
Eva Wagner-Drouet
Principal Investigator Email
eva.wagner@unimedizin-mainz.de
Contact Person Name
Eva Wagner-Drouet
Contact Person Email
eva.wagner@unimedizin-mainz.de
Site Name
National Center For Tumor Diseases (NCT) Heidelberg
Principal Investigator Name
Guy Ungerechts
Principal Investigator Email
guy.ungerechts@nct-heidelberg.de
Contact Person Name
Guy Ungerechts
Site Name
University Medical Center Hamburg-Eppendorf
Department Name
II. Medizinische Klinik
Principal Investigator Name
Winfried Henning Alsdorf
Principal Investigator Email
w.alsdorf@uke.de
Contact Person Name
Winfried Henning Alsdorf
Contact Person Email
w.alsdorf@uke.de
Site Name
Universitaetsklinikum Regensburg AöR
Department Name
Klinik und Poliklinik für Innere Medizin III
Principal Investigator Name
Daniel Heudobler
Principal Investigator Email
daniel.heudobler@ukr.de
Contact Person Name
Daniel Heudobler
Contact Person Email
daniel.heudobler@ukr.de
Site Name
Medizinische Hochschule Hannover
Department Name
Klinik für Hämatologie, Hämaostaseologie,Onkologie und Stammzelltransplantation
Principal Investigator Name
Florian Heidel
Principal Investigator Email
heidel.florian@mh-hannover.de
Contact Person Name
Florian Heidel
Contact Person Email
heidel.florian@mh-hannover.de

Sponsor

Primary sponsor

Full Name
BioNTech Cell & Gene Therapies GmbH
Organisation Type
Pharmaceutical company
Country Of Registered Address
Germany

Contract research organisations

Name
Icon Public Limited Company
Responsibilities
Clinical Research Organization

Third parties

  • {"country":"Austria","full_name":"Abf Pharmaceutical Services GmbH","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"Mlm Medical Labs GmbH","duties_or_roles":"code:4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Ventana Medical Systems Inc.","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Medidata Solutions International Limited","duties_or_roles":"RTSM & EDC Support","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"BioKryo GmbH","duties_or_roles":"Sample Storage","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"Frigo-Trans GmbH","duties_or_roles":"IMP Storage","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"Precision for Medicine GmbH","duties_or_roles":"RTSM & EDC Support","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"Germany","full_name":"ProtaGene CGT GmbH","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
  • {"country":"Netherlands","full_name":"Pharmaceutical Research Associates Group B.V.","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Personalis Inc.","duties_or_roles":"code:4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"Ireland","full_name":"Icon Public Limited Company","duties_or_roles":"Clinical Research Organization","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
BNT211 (CLDN6 CAR-T)
Active Substance
CLDN6 CAR-T
Modality
Cell therapy
Routes Of Administration
INTRAVENOUS BOLUS USE
Route
INTRAVENOUS BOLUS USE
First In Human
Yes
Maximum Dose
1000000000 (unit: Other)
Investigational Product Name
BNT211 (CLDN6 CAR-T(A))
Active Substance
CLDN6 CAR-T(A)
Modality
Cell therapy
Routes Of Administration
INTRAVENOUS BOLUS USE
Route
INTRAVENOUS BOLUS USE
First In Human
Yes
Maximum Dose
500000000 (unit: Other)
Investigational Product Name
BNT211 (CLDN6 RNA-LPX)
Active Substance
CLDN6 RNA-LPX
Modality
Other RNA
Routes Of Administration
INTRAVENOUS BOLUS USE
Route
INTRAVENOUS BOLUS USE
First In Human
Yes
Maximum Dose
200 µg (max daily); max total 3550 µg
Investigational Product Name
BNT211 (RBP030.2)
Active Substance
RBP030.2
Modality
Other RNA
Routes Of Administration
INTRAVENOUS BOLUS USE
Route
INTRAVENOUS BOLUS USE
First In Human
Yes
Maximum Dose
100 µg (max daily); max total 1775 µg
Combination Treatment
Yes

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