Response features, efficacy and safety of CD318-targeted CAR-T cell therapy against pancreatic cancer – ResCPa study

In order to study feasibility, safety and (preliminary) efficacy for CD318-CAR-T cell therapy against PDAC we will perform a multicentric phase I/IIa clinical study in patients (n = max. 38 [for all dose escal.]) with metastatic or locally advanced PDAC refractory or ineligible to SoC in four participating clinical centers with expertise in CAR-T cell therapy and early clinical trials in oncology (Tübingen, Heidelberg, Freiburg, Würzburg). We will screen patients for eligibility at each center, e.g., through tumor conferences, and, subsequently, carry out an expression screen of CD318 on PDAC (Institute of Pathology, Tübingen). Leukapheresis will be performed at each center, and the CD318-CAR-T cell product will be manufactured at the GMP cell therapeutics facility Tübingen. After lymphodepletion by cyclophosphamide and nab-paclitaxel, CD318-CAR-T cells will be administered i.v. as single dose or dual dosing (q2w) in escalating doses in a 3+3 study design (part I, n = max. 30 pat.) and as dual dosing with R2PD in an expansion cohort (part II, n = 8 pat.) (see Appendix). Patient follow-up will be carried out for 12 months with safety monitoring (incl. immune-related toxicities) and assessment of tumor responses (day 30, months 3, 6, 9 & 12) by CT/MRI imaging, serum tumor markers and circulating tumor DNA. Tumor biopsies taken before and after CAR-T cell infusion will be assessed regarding changes in PDAC muta-tional burden. Expansion, persistence and (potentially) exhaustion of circulating CD318-CAR-T cells will be monitored after infusion using flow cytometry – based immunomonitoring.

Status: In Vorbereitung

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