A study to learn about the safety and efficacy of the study drug product CLDN6 CAR-T with/without the second study drug product CLDN6 RNA-LPX in patients with a specific type of advanced cancer that has reoccurred and does not respond to standard of care treatment.

Phase 1

Conditions: CLDN6-positive relapsed or refractory advanced solid tumors
MedDRA version: 21.0Level: LLTClassification code 10043302Term: Testicular cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0Level: PTClassification code 10033128Term: Ovarian cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.1Level: PTClassification code 10017758Term: Gastric cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.0Level: PTClassification code 10046766Term: Uterine cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.0Level: LLTClassification code 10007460Term: Carcinoma of unknown primarySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.1Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2019-004323-20-DE

Lead Sponsor: BioNTech Cell & Gene Therapies GmbH

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 150

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

-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.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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