Sponsor decision

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.

The study will consist of two parts. The Safety Lead-in Part will evaluate safety and tolerability of CLDN6 CAR T ± CLDN6 RNA-LPX therapy in three arms with different dosing regimens. In the Safety Lead-in Part, participants will be randomized in a 1:1:1 ratio. Data from the Safety Lead-in Part up to the cut off will be used to select the dose for the single-arm Main Part of the study.

To increase the potency of the transferred CAR-T cells, a lymphodepleting chemotherapy regimen (comprising fludarabine and cyclophosphamide) will be administered in participants prior to infusion of CLDN6 CAR-T.

It is expected that it will take approximately 28 months for each participant to complete screening, apheresis, pre-treatment, treatment, and primary follow-up.

Participants who receive a CLDN6 CAR-T infusion will complete the long-term follow-up (LTFU) to assess safety and efficacy of the CLDN6 CAR-T treatment for a total of 15 years after CLDN6 CAR-T infusion. No investigational medicinal product (IMP) will be administered during the LTFU.

Key Inclusion Criteria:

• 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.

Key Exclusion Criteria:

• 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 cardiac conditions defined as exclusionary per protocol.
• Have any concurrent conditions that could pose an undue medical hazard or interfere with the interpretation of the study results.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.