CLDN6-positive relapsed or refractory advanced solid tumors MedDRA version: 21.0 Level: LLT Classification code 10043302 Term: Testicular cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10033128 Term: Ovarian cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10017758 Term: Gastric
Conditions
Interventions
Product Name: CLDN6 CAR-T
Product Code: CG001.2
Pharmaceutical Form: Dispersion for infusion
INN or Proposed INN: CG001.2
Current Sponsor code: CG001.2
Other descriptive name: CLDN6 CAR-T
Concentrati
Sponsors
BioNTech Cell & Gene Therapies GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For Parts 1, 2 and 3: -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 for specific detection of CLDN6 protein expression in formalin-fixed, paraffin-embedded neoplastic tissues. -Must have measurable disease per RECIST 1.1 (except for germ cell tumours). -Germ cell cancer patients without initial measurable disease per RECIST 1.1 and evaluable by cancer antigen (CA)-125, Alphafetoprotein (AFP) or hCG (as applicable] are eligible for the trial. For Parts 1 and 2: -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. For Part 2 only: Cohort 7: Vaccine-modulated CLDN6 CAR-T/CLDN6 CAR-T(A) without lymphodepletion - 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. For Part 3 only: Cohort 1: Testicular cancer -Histologically or cytologically tumor of the testis of any histological subtype that has relapsed and/or is refractory to standard therapy. There is no limit on the number of prior treatment regimens Cohort 2: Ovarian cancer -Histologically or cytologically confirmed ovarian cancer of any histology type including primary peritoneal or fallopian tube tumor that is resistant to a platinum-based chemotherapy regimen. There is no available standard therapy likely to confer clinical benefit to the patient, or they are not a candidate for such available therapy. There is no limit on the number of prior treatment regimens. - Patients without initial measurable disease per RECIST 1.1 and evaluable by CA-125 are eligible for the trial and the tumor response will be assessed by Gynecologic Cancer Intergroup (GCIG) criteria for evaluation of best overall response in patients without initial measurable disease and evaluable by CA-125. Cohort 3: Gastric cancer -Histologically or cytologically confirmed inoperable or metastatic gastric cancer that has failed or demonstrated intolerance to standard therapy - which includes platinum or fluoropyrimidine or taxane based chemotherapy. Human epidermal growth factor receptor 2 (HER2)-positive gastric cancer patient must have failed or demonstrated intolerance to HER2-targeting treatment. There is no limit on the number of prior treatment regimens. Cohort 4: Endometrial cancer -Histologically or cytologically confirmed Endometrial cancer of any histology type that is resistant to a platinum-based chemotherapy regimen, or for whom there is no available standard therapy likely to confer clinical benefit, or patient is not a candidate for such available therapy. There is no limit on the number of prior treatment regimens. Cohort 5: NSCLC -Histological or cytological diagnosis of metastatic non-squamous NSCLC and must have progressed on the standard therapy, including platinum-based chemotherapy and/or checkpoint inhibitor therapy. Patient with epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), receptor tyrosine kinase encoded by gene ROS-1 (ROS-1) or human gene encoding proto-oncogene B-Raf (BRAF) mut
Exclusion criteria
Exclusion criteria: -Has received prior CAR-T therapy, except CLDN6 CAR-T/CLDN6 CART(A) therapy. -Has received vaccination with live virus vaccines within 6 weeks prior to the start of LD. -Receives concurrent systemic (oral or intravenous [i.v.]) steroid therapy > 10 mg prednisolone daily, or its equivalent, for an underlying condition. -Current evidence of new or growing brain or spinal metastases during screening. Patients with known brain or spinal metastases may be eligible if they: -Had radiotherapy or another appropriate therapy for the brain or spinal metastases, -Have no neurological symptoms, -Have stable brain or spinal disease on the computer tomography or magnetic resonance imaging scan within 4 weeks before signing of the informed consent, -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), -Do not require steroid therapy within 7 d before the first dose of CLDN6 CAR-T/CLDN6 CAR-T(A), -Spinal bone metastases are allowed, unless imminent fracture or cord compression is anticipated. -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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: NOTE FOR THE READER CLDN6 (mod)RNA-LPX is used in this document to refer to both CLDN6 RNA-LPX and CLDN6 modRNA-LPX: -To assess the safety and tolerability of CLDN6 CAR-T / CLDN6 CAR-T(A) +/- CLDN6 (mod)RNA-LPX and to assess the comparability of CLDN6 CAR-T and CLDN6 CAR-T(A) -To identify the maximum tolerated dose (MTD)/RP2D for each IMP (i.e. CLDN6 CAR-T/CLDN6 CAR-T(A) +/- CLDN6 modRNA-LPX) based on the occurrence of dose-limiting toxicities (DLT) using the following definitions: -MTD is defined as the highest tolerated dose of CLDN6 CAR-T/CLDN6 CAR-T(A) +/- CLDN6 modRNA-LPX where less than 33% of the patients experience a DLT -Recommended phase 2 dose (RP2D) of CLDN6 CAR-T/CLDN6 CAR-T(A) +/- CLDN6 modRNA-LPX based on integrated evaluation of safety and other data for all dose levels tested;Secondary Objective: NOTE FOR THE READER CLDN6 (mod)RNA-LPX is used in this document to refer to both CLDN6 RNA-LPX and CLDN6 modRNA-LPX. -To describe the profile of soluble immune factors in CLDN6 CAR-T/CLDN6 CAR-T(A) +/- CLDN6 modRNA-LPX -To evaluate anti-tumor activity of CLDN6 CAR-T/CLDN6 CAR-T(A) +/- CLDN6 modRNA-LPX according to response evaluation criteria in solid tumors version 1.1 (RECIST 1.1);Primary end point(s): -Occurrence of treatment-emergent adverse events (TEAEs) within a patient including = Grade 3, serious, fatal TEAEs by relationship -Occurrence of dose reduction and discontinuation of investigational medicinal product (IMP) within a patient due to TEAEs -Occurrence of DLTs within a patient during the DLT evaluation period. ;Timepoint(s) of evaluation of this end point: -During the DLT evaluation period (a minimum of 28 days after the first dose). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -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 RECIST 1.1) is observed as best overall response -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 -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 (PD per RECIST 1.1)/recurrence or death from any cause, whichever occurs first;Timepoint(s) of evaluation of this end point: -During the treatment phase and primary follow up period (refer to the schedule of trial procedures in the protocol for further details). | — |
Countries
Germany, Netherlands, Sweden
Contacts
Public ContactLiane Monica Preußner
BioNTech Cell & Gene Therapies GmbH
Outcome results
None listed