Abstract 2071
Background
Chimeric antigen receptor (CAR) T cell therapy of solid tumors has not yet met the success seen in hematologic cancers. Many challenges include the antigen targeted, on-target off-tumor toxicity, an immune suppressive environment, and product manufacturing hurdles for timely delivery of treatment to the patient. Also, repeat multi dosing is limited with current viral-based CAR T therapies. MaxCyte has developed its first CAR product, MCY-M11, applying the CARMA™ non-viral, mRNA-based platform for rapid (<1 day) manufacturing with efficient transfection of a human scFv targeting mesothelin, using fresh non-expanded peripheral blood mononuclear cells for autologous cell therapy. Mesothelin is an attractive target highly expressed in many solid tumors vs. low expression in mesothelium of mostly non-critical tissues. The transient expression of the CAR is intended to limit potential excessive or unwanted toxicity, allowing for multiple therapeutic infusions to facilitate a more effective immune response. In a mouse model, MCY-M11 cells had the ability to traffic to and inhibit growth of mesothelin-expressing ovarian cancer and improve survival, both in a dose-dependent manner and with multicycle administration. The first in human study of MCY-M11 in patients with ovarian cancer and peritoneal mesothelioma (NCT03608618) is described.
Trial design
This 3 + 3 phase I tests 4 ascending cell dose levels, in patients with relapsed/refractory adenocarcinoma of the ovary, fallopian tube, primary peritoneum, or peritoneal mesothelioma. At least 15 patients will be enrolled to receive one cycle of 3 weekly doses (D1, D8, D15) of intraperitoneal MCY-M11. The primary objective is safety (incidence and severity of adverse events per NCI CTCAE v5.0), tolerability, and feasibility of infusion of MCY-M11. Secondary objectives: antitumor activity (RECIST, irRECIST, tumor markers), correlates of CAR performance, and host immune activation. The study is conducted at two sites. The first patient was dosed in October 2018, recruitment is ongoing.
Clinical trial identification
NCT03608618.
Editorial acknowledgement
Legal entity responsible for the study
MaxCyte Inc.
Funding
MaxCyte Inc.
Disclosure
C. Annunziata: Advisory / Consultancy: MaxCyte. C. Dansky-Ullmann: Full / Part-time employment: MaxCyte. D. Weng: Advisory / Consultancy: MaxCyte Inc; Advisory / Consultancy: Kite Pharma; Advisory / Consultancy: Puma Biotech; Advisory / Consultancy: Genentech. J. Vanas: Full / Part-time employment: MaxCyte. R. Keefe: Full / Part-time employment: MaxCyte. M. Kuo: Full / Part-time employment: MaxCyte. P. Thaker: Shareholder / Stockholder / Stock options: Celsion; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Clovis; Advisory / Consultancy: Iovance; Advisory / Consultancy: Immunogen; Advisory / Consultancy: AstraZeneca; Speaker Bureau / Expert testimony: Merck; Speaker Bureau / Expert testimony: Tesaro. All other authors have declared no conflicts of interest.
Resources from the same session
4692 - Immune cell biomarkers on neo-adjuvant chemo-immunotherapy treatment for resectable stage IIIA NSCLC patients
Presenter: Raquel Laza-Briviesca
Session: Poster Display session 3
Resources:
Abstract
1707 - Clinical utility of precision immunoprofiling and monitoring of the tumor microenvironment using flow cytometry and CyTOF in patients with advanced NSCLC treated with atezolizumab: results from a phase II study for biomarker analysis (EPOC1702)
Presenter: Keisuke Kirita
Session: Poster Display session 3
Resources:
Abstract
3594 - Tumor mutation burden (TMB), PD-L1, IFN-γ signaling identify subgroups of patients (pts) who benefit from durvalumab (D, anti-PDL1) or D and tremelimumab (T, anti-CTLA4) treatment in urothelial bladder cancer (UC)
Presenter: Christophe Massard
Session: Poster Display session 3
Resources:
Abstract
744 - The decrease of TMB, TNB and HLA expression are the Mechanism of Drug Resistance of NSCLC to immunosuppressive PD-1/PD-l1.
Presenter: Sheng Yu
Session: Poster Display session 3
Resources:
Abstract
2350 - Eosinophilia during treatment of immune checkpoint inhibitors (ICIs) predicts succeeding onset of immune-related adverse events (irAEs)
Presenter: Rika Kizawa
Session: Poster Display session 3
Resources:
Abstract
5930 - A transcriptomic immunologic signature predicts favorable outcome in neoadjuvant chemotherapy treated triple negative breast tumors.
Presenter: Javier Pérez-peña
Session: Poster Display session 3
Resources:
Abstract
6127 - Alterations of TMB and TCR repertoires during Chemotherapy in East Asian lung cancer patients without TKI-related driver gene mutations
Presenter: Lele Song
Session: Poster Display session 3
Resources:
Abstract
1310 - Association of SCFA in gut microbiome and clinical response in solid cancer patients treated with andi-PD-1 antibody.
Presenter: Motoo Nomura
Session: Poster Display session 3
Resources:
Abstract
2286 - Extracellular matrix and tissue derived metabolites in a liquid biopsy identifies endotypes of metastatic melanoma patients with differential response to immune checkpoint inhibitor treatment
Presenter: Nicholas Willumsen
Session: Poster Display session 3
Resources:
Abstract
4107 - Pathologic scoring of pre-treatment H&E biopsies predicts overall survival in patients with metastatic clear cell renal cell carcinoma receiving nivolumab monotherapy
Presenter: Julie Stein
Session: Poster Display session 3
Resources:
Abstract