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
4489 - A Window of Opportunity Trial of Atorvastatin Targeting p53 Mutant Malignancies
Presenter: Joaquina Baranda
Session: Poster Display session 3
Resources:
Abstract
1945 - Randomized Phase II Study of Trabectedin/Olaparib Compared to Physician’s Choice in Subjects with Previously Treated Advanced or Recurrent Solid Tumors Harboring DNA Repair Deficiencies.
Presenter: Christoph Heilig
Session: Poster Display session 3
Resources:
Abstract
3021 - Homogenisation of Leftover Surgical Tissue across multiple cancer types: a Feasibility Study (HoLST-F)
Presenter: Lavinia Spain
Session: Poster Display session 3
Resources:
Abstract
2882 - Safety, efficacy, and immune effects of intratumoral tilsotolimod in patients with refractory solid tumors: updated results from ILLUMINATE-101
Presenter: Hani Babiker
Session: Poster Display session 3
Resources:
Abstract
1950 - Phase 1 Dose Escalation of MSC-1, a humanized anti-LIF monoclonal antibody, in patients (pts) with advanced solid tumors: Updated results
Presenter: Erkut Borazanci
Session: Poster Display session 3
Resources:
Abstract
2391 - A phase 1 study of Sym021, an anti-PD-1 antibody (Ab), alone and in combination with Sym022 (anti-LAG-3) or Sym023 (anti-TIM-3)
Presenter: Anna Spreafico
Session: Poster Display session 3
Resources:
Abstract
5692 - FPA150 (B7-H4 antibody) Phase 1 Update in Advanced Solid Tumors: Monotherapy and in Combination with Pembrolizumab
Presenter: Zev Wainberg
Session: Poster Display session 3
Resources:
Abstract
2416 - MG1124, a novel CEACAM1-targeted monoclonal antibody, has therapeutic potential as a combination partner of PD-1 inhibitors in NSCLC patients
Presenter: Eun Hee Lee
Session: Poster Display session 3
Resources:
Abstract
2661 - Tumor stroma targeting and modulation by OMTX705 ADC, a novel and potent immunotherapeutic treatment of solid tumors.
Presenter: Myriam Fabre
Session: Poster Display session 3
Resources:
Abstract
3681 - Durvalumab + monalizumab, mFOLFOX6, and bevacizumab in patients (pts) with metastatic microsatellite-stable colorectal cancer (MSS-CRC)
Presenter: May Cho
Session: Poster Display session 3
Resources:
Abstract