A Clinical Study Investigating the Therapeutic Effects and Safety of an Investigational Cell Therapy Given With and Without an Additional Investigational Product in Males With Testicular Cancer or a Form of Cancer That Developed From Sperm

NCT06940804 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: BNT211-022024-511941-20-00
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is designed to evaluate the safety, efficacy, cellular kinetics, and immunogenicity of Claudin 6 (CLDN6) Chimeric antigen receptor T cell (CAR-T) ± CLDN6 ribonucleic acid-lipoplex (RNA-LPX) in participants born male with relapsed or refractory CLDN6-positive testicular or extragonadal germ cell tumors (GCTs) after prior salvage therapy.

Conditions

Testicular Germ Cell Tumor; Extragonadal Germ Cell Tumor

Keywords

Advanced germ cell tumor; Metastatic germ cell tumors; CLDN6-positive relapsed or refractory advanced solid tumors; Salvage therapy; Testicular cancer; Immunotherapy; Autologous T-cells

Outcome Measures

Primary Outcomes (3)

• Safety Lead-in Part: Occurrence of treatment emergent adverse events (TEAEs) including Grade ≥3, adverse events of special interest (AESIs) and serious or fatal TEAEs by casual relationship to study treatment

  For each treatment arm

  Up to 110 weeks after first dose of IMP

• Main Part: Overall response rate (ORR) assessed by the blinded independent central review (BICR)

  Defined as the percentage of participants in whom a confirmed complete response (CR) or partial response (PR) (per response evaluation criteria in solid tumors version 1.1 (\[RECIST 1.1\]) is observed as best overall response

  Up to 110 weeks after first dose of IMP

• LTFU: Occurrence of AEs suspected to be related to CLDN6 CAR-T

  AEs may include: new malignancy (hematologic or solid) from genetically modified cells; new neurologic disorder, or exacerbation of a pre-existing disorder; new rheumatologic or autoimmune disorder, or exacerbation of a prior rheumatologic or other autoimmune disorder; new hematologic disorder; other new clinical condition considered by the investigator to be related to the prior genetically engineered T-cell therapy.

  Up to 15 years after CLDN6 CAR-T administration

Secondary Outcomes (18)

• Safety Lead-in and Main Part: Occurrence of TEAEs including Grade ≥3, AESIs, and serious or fatal TEAEs by casual relationship to study treatment

  From first dose of IMP until 90 days after last dose of IMP, or until a new anticancer therapy is started, whichever occurs first

• Safety Lead-in and Main Part: Geometric mean of pharmacokinetic parameter maximum concentration (Cmax) of CLND6 CAR-T

  Up to 97 weeks after first IMP dose

• Main Part: Geometric mean of pharmacokinetic parameter Cmax of interleukin (IL)-6

  Up to 97 weeks after first IMP dose

• Safety Lead-in and Main Part: Geometric mean of pharmacokinetic parameter time to maximum concentration (Tmax) of CLND6 CAR-T

  Up to 97 weeks after first IMP dose

• Main Part: Geometric mean of pharmacokinetic parameter Tmax of IL-6

  Up to 97 weeks after first IMP dose

Study Arms (4)

Safety Lead-in Part - CLDN6 CAR-T (dose level 1) + CLDN6 RNA-LPX

EXPERIMENTAL

Biological: CLDN6 CAR-T; Biological: CLDN6 RNA-LPX

Safety Lead-in Part - CLDN6 CAR-T (dose level 2)

EXPERIMENTAL

Biological: CLDN6 CAR-T

Safety Lead-in Part - CLDN6 CAR-T (dose level 2) + CLDN6 RNA-LPX

EXPERIMENTAL

Biological: CLDN6 CAR-T; Biological: CLDN6 RNA-LPX

Main Part - Selected dose of CLDN6 CAR-T + CLDN6 RNA-LPX

EXPERIMENTAL

Doses as selected from the Safety Lead-in Part

Biological: CLDN6 CAR-T; Biological: CLDN6 RNA-LPX

Interventions

CLDN6 CAR-T BIOLOGICAL

Intravenous (IV) infusion

Main Part - Selected dose of CLDN6 CAR-T + CLDN6 RNA-LPX; Safety Lead-in Part - CLDN6 CAR-T (dose level 1) + CLDN6 RNA-LPX; Safety Lead-in Part - CLDN6 CAR-T (dose level 2); Safety Lead-in Part - CLDN6 CAR-T (dose level 2) + CLDN6 RNA-LPX

CLDN6 RNA-LPX BIOLOGICAL

IV injection

Main Part - Selected dose of CLDN6 CAR-T + CLDN6 RNA-LPX; Safety Lead-in Part - CLDN6 CAR-T (dose level 1) + CLDN6 RNA-LPX; Safety Lead-in Part - CLDN6 CAR-T (dose level 2) + CLDN6 RNA-LPX

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have a histologically confirmed diagnosis of a testicular or extragonadal GCT of extracranial origin.
• Evidence of measurable disease by RECIST 1.1 or if RECIST 1.1 evaluation is not possible, elevation of serum tumor marker(s) (AFP or βhCG).
• Participants with evidence of progressive or recurrent metastatic GCT defined as meeting at least one of the following criteria:
• Tumor biopsy of new or growing or unresectable lesions demonstrating viable non-teratomatous GCT. In the event of an incomplete gross resection where viable GCT is found, participants will be considered eligible for this study.
• Elevated serum tumor markers (AFP or ßhCG) that are increasing. Increase of an elevated lactate dehydrogenase alone does not constitute progressive disease.
• Development of new or enlarging lesions in the setting of persistently elevated AFP or ßhCG, even if the markers are not continuing to rise.
• Participants must have received prior high-dose chemotherapy with autologous stem cell transplantation or conventional dose chemotherapy as salvage therapy. There is no maximum limit for the number of prior treatments.
• Have a CLDN6-positive tumor assessed using an analytically validated immunohistochemistry assay at a central laboratory.
• Have an Eastern Cooperative Oncology Group performance status of 0 to 1.
• Have laboratory tests of adequate organ function as defined in the protocol.

You may not qualify if:

• Had major surgery within the 4 weeks before the first dose of study treatment.
• Have received a prior CLDN6 CAR-T therapy.
• Are receiving systemic (oral or IV) steroid therapy \>10 mg prednisolone daily, or its equivalent, for an underlying condition.
• Have unresolved side effects of any prior therapy or procedures not recovered to CTCAE version 5.0 Grade 1 or lower, except for AEs not constituting a safety risk by investigator judgment.
• Have a pure teratoma, or pure teratoma with somatic-type malignancy or a combination of these histologies without any additional histologic subtype.
• Have current evidence of active and/or uncontrolled brain or spinal metastases.
• Have an active autoimmune disease or any active immunologic disorder requiring immunosuppression with steroids or other immunosuppressive agents (protocol-defined exceptions apply). Note: Participants may be included if their disease is well controlled without the use of immunosuppressive agents, at the discretion of the investigator.
• Have a history of another primary cancer within the 24 months prior to signing the main informed consent form (exceptions for definitely treated malignancies that have been in complete remission for more than 24 months apply).
• Receipt of allogeneic stem cell transplantation in the 5 years prior to study enrollment.
• Have any concurrent conditions that could pose an undue medical hazard or interfere with the interpretation of the study results.

Sponsors & Collaborators

• BioNTech SE: lead

MeSH Terms

Conditions

Testicular Germ Cell Tumor; Neoplasms, Germ Cell and Embryonal; Testicular Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases; Endocrine System Diseases; Testicular Diseases; Gonadal Disorders

Study Officials

• BioNTech Responsible Person

  BioNTech SE

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2025
• First Posted: April 23, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): June 1, 2042
• Study Completion (Estimated): June 1, 2042
• Last Updated: July 2, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share