Study design and execution, patient selection and treatment
Tumors, tumor
TUMOR, SPINAL METASTASES, DISEASE, SOLID TUMORS, TUMORS, SECONDARY, ONCOLOGY
The study design comprises a dose escalation part and a dose expansion part with indication-specific cohorts including GCT, EOC and other indications to start when the recommended phase 2 dose (RP2D) obtained with the dedicated phase 2 manufacturing process is defined.The primary endpoints for the dose escalation part are to characterize the safety and tolerability of CLDN6 CAR-T cells ± CARVac and to identify the maximum tolerated dose (MTD)/RP2D. Evaluation of the antitumor activity of CLDN6 CAR-T cells ± CARVac per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 and characterization of soluble immune factors (cytokines) induced by treatment are the secondary endpoints. An MTD/RP2D was not established, as dose escalation is being repeated with CAR-T cells manufactured with an automated manufacturing process.The dose expansion part of the study enrolled adults diagnosed with advanced metastatic solid tumors of any type lacking further systemic treatment options, Eastern Cooperative Oncology Group (ECOG) 0–1 and measurable disease per RECIST 1.1. Patients with new or growing brain or spinal metastases during screening were excluded. Patients for the study were recruited from a CLDN6 prescreening. Additional eligibility criteria are noted in the Of 180 patients prescreened for CLDN6 expression with a semiquantitative immunohistochemistry assay between September 2020 and November 2021, 54 (30%) met the inclusion criteria for tumor CLDN6 positivity defined as ≥50% of tumor cells displaying an intermediate (2+) or strong (3+) membrane staining intensity (Fig. 