Abstract 5047
Background
Malignant pleural mesothelioma (MPM) is a cancer with a worldwide increasing incidence due to the use of asbestos. MPM is incurable despite the use of multimodality treatment. Tumor spread confined to the thoracic cavity is a hallmark of MPM, providing a rational for local treatment. We developed a chimeric antigen receptor (CAR) targeting FAP (fibroblast activating protein), a cell-surface antigen that we have shown to be highly expressed in epithelial cancers.
Methods
Using a Δ-CD28-costimulated CAR, we initiated a phase I clinical trial (NCT01722149) to determine the safety and persistence of intra-pleural administered anti-FAP-CAR T cells in the periphery. A single dose of 1x 106 re-directed T cells was administered through a pleural catheter. Patients were monitored on an intensive care unit for 48h. Clinical evaluations of on-target and off-tumor toxicity were assessed for 3 months. Laboratory analyses included cytokines, CRP and the detection of CAR-T cells in the pleural effusion and blood over time. Radiological evaluation with PET-CT scans was performed as standard of care.
Results
Three patients with metastatic MPM were treated (all patients received at least two cycles of chemotherapy previous to CAR T-cell administration). No CAR T-cell-related toxicities were observed. Intense monitoring for cytokine release syndrome showed significant changes on a subset of cytokines. CAR T-cells were detected in the peripheral blood after treatment. Activity of the patient’s redirected T cells was confirmed in vitro. Furthermore, one patient received an anti-PD1 checkpoint blockade antibody 8 months after CAR T-cell instillation with no toxicity. With a median follow-up of 18 months, 2 out of 3 patients are alive.
Conclusions
In this phase I clinical trial, intra-pleural administration of anti-FAP CAR T-cells was well tolerated without any evidence of treatment related toxicity. Persistence of CAR T-cells was documented in the periphery.
Clinical trial identification
NCT01722149.
Editorial acknowledgement
Legal entity responsible for the study
Unviersity Hospital Zurich.
Funding
Swiss Cancer League.
Disclosure
A. Curioni: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: F. Hoffmann-La Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Merck Sharp and Dohme; Advisory / Consultancy: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer ; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Takeda . C. Britschgi: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Takeda. W. Weder: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Medtronic. R.A. Stahel: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy: AbbVie; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Officer / Board of Directors: F. Hoffmann-La Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Merck Sharp and Dohme; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Officer / Board of Directors: Takeda; Research grant / Funding (institution): Genentech. All other authors have declared no conflicts of interest.
Resources from the same session
2963 - Analytical performance of the Resolution-HRD plasma assay used to identify mCRPC patients with biallelic disruption of DNA repair genes for treatment with niraparib
Presenter: Ira Pekker
Session: Poster Display session 3
Resources:
Abstract
3523 - Results of a global external quality assessment scheme for EGFR testing on liquid biopsy
Presenter: Nicola Normanno
Session: Poster Display session 3
Resources:
Abstract
3295 - Clinical impact of plasma Next-Generation Sequencing (NGS) in advanced Non-small cell lung cancer (aNSCLC)
Presenter: Laura Bonanno
Session: Poster Display session 3
Resources:
Abstract
5632 - Feasibility study of a ctEGFR prototype assay on the fully automated Idylla™ platform
Presenter: Martin Reijans
Session: Poster Display session 3
Resources:
Abstract
3614 - Enhanced Access to EGFR Molecular Testing in NSCLC using a Cell-Free DNA Tube for Liquid Biopsy
Presenter: Theresa May
Session: Poster Display session 3
Resources:
Abstract
5664 - Analysis of circulating tumor DNA in paired plasma and sputum samples of EGFR-mutated NSCLC patients
Presenter: Christina Grech
Session: Poster Display session 3
Resources:
Abstract
4945 - Liquid biopsy and Array Comparative Genomic Hybridization (aCGH)
Presenter: Panagiotis Apostolou
Session: Poster Display session 3
Resources:
Abstract
5746 - Next-generation sequencing panel verification to detect low frequency single nucleotide and copy number variants from mixing cell line studies
Presenter: Rocio Rosas-Alonso
Session: Poster Display session 3
Resources:
Abstract
5901 - Automated rarefaction analysis for precision B and T cell receptor repertoire profiling from peripheral blood and FFPE-preserved tumor
Presenter: Luca Quagliata
Session: Poster Display session 3
Resources:
Abstract
2027 - A Heptamethine cyanine dye is a potential diagnostic marker for Myeloid-Derived Suppressor Cells
Presenter: Chaeyong Jung
Session: Poster Display session 3
Resources:
Abstract