CD318-targeted CAR-T Cell Therapy in Patients With Pancreatic Cancer (ResCPa)

Summary

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, with limited therapeutic options and a five-year survival rate below 10 % in advanced stages. Standard treatments, such as multi-agent chemotherapy, provide only marginal survival benefits and are often associated with significant toxicity. Novel approaches are urgently needed.

The ResCPa study is a first-in-human, multicenter, phase I/IIa investigator-initiated trial evaluating the safety, feasibility, and preliminary efficacy of autologous CD318-targeted chimeric antigen receptor (CAR) T-cell therapy in patients with metastatic or locally advanced PDAC that has progressed after standard-of-care treatment. CD318 (also known as CDCP1) is highly expressed in primary and metastatic PDAC tissue but rarely found in healthy tissues, making it a promising and potentially safe immunotherapy target. Preclinical studies have shown potent anti-tumor activity of CD318-CAR-T cells in vitro and in PDAC mouse models without target-specific toxicity.

Eligible patients will undergo tumor tissue screening for CD318 expression. Those meeting the criteria will proceed to leukapheresis for autologous T-cell collection. The CD318-CAR construct, optimized in preclinical work, will be introduced via a GMP-produced lentiviral vector, and CAR-T cells will be expanded using automated manufacturing (CliniMACS Prodigy). Following lymphodepleting chemotherapy, patients will receive CD318-CAR-T cells in a dose-escalation design to determine the recommended phase II dose, with the option of dual dosing.

The primary objectives are to assess safety, tolerability, and feasibility of manufacturing and delivering CD318-CAR-T cells. Secondary objectives include preliminary anti-tumor activity (objective response rate, progression-free survival, overall survival), CAR-T cell expansion and persistence, and immunological correlates of response or resistance. Patients will be followed for at least 12 months post-infusion, with extended safety follow-up per regulatory requirements.

In parallel, an extensive translational research program will investigate CAR-T cell phenotypes, tumor microenvironment changes, and mechanisms of treatment resistance using single-cell multi-omics, spatial proteomics and transcriptomics, organoid co-culture models, and microbiome profiling. Insights from these studies aim to guide optimization of next-generation CAR-T therapies for PDAC and other solid tumors.

This trial is conducted by a German academic-industrial consortium including the University Hospital Tübingen, Miltenyi Biotec, University Hospital Freiburg, Klinikum rechts der Isar (TUM), Berlin Institute of Health (BIH), and other partners. The study is supported by the German Federal Ministry of Education and Research (BMBF) within the "National Decade Against Cancer" initiative.

Conditions

• Carcinoma, Pancreatic Ductal
• Pancreatic Neoplasms

Interventions

BIOLOGICAL

CD318-CAR-T cells

Autologous T cells collected by leukapheresis, genetically modified using a GMP-manufactured lentiviral vector encoding a fully human CD318-specific chimeric antigen receptor (CAR), and expanded on the CliniMACS Prodigy system. After lymphodepleting chemotherapy (fludarabine/cyclophosphamide), participants receive (Phase I) a single CAR-T infusion per BOIN dose-escalation to determine MTD/RP2D; (Phase IIa) an expansion at RP2D with a predefined dual-dosing schedule (two infusions) separated by a protocol-defined interval.

Sponsors & Collaborators

• University Hospital Freiburg

  collaborator OTHER

• Technical University of Munich

  collaborator OTHER

• National Center for Tumor Diseases, Heidelberg

  collaborator OTHER

• Wuerzburg University Hospital

  collaborator OTHER

• Berlin Institute of Health

  collaborator OTHER

• Miltenyi Biotec B.V. & Co. KG

  collaborator INDUSTRY

• University Hospital Tuebingen

  lead OTHER

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-07-31

Primary Completion

2028-12-31

Completion

2028-12-31