Abstract CT159: A phase 1 study of intraperitoneal MCY-M11 therapy for women with platinum resistant high grade serous adenocarcinoma of the ovary, primary peritoneum, or fallopian tube, or subjects with peritoneal mesothelioma with recurrence after prior chemotherapy
Authors: Ghobadi Armin , Thaker Premal , Weng David , Vanas Julie , Ekwede Irene , Pavlova Mira , Keefe Robert , Kuo Michael , Ullmann Claudio Dansky , Hassan Raffit , Annunziata Christina 
Published: August 2019

Abstract
Background: Chimeric antigen receptor CAR T cell therapy for solid tumors has not yet achieved the success seen in hematologic malignancies. Many challenges remain, including the type of antigen being targeted, the risk for on-target off-tumor toxicity, a frequent high degree of immune tolerance within an immune suppressive environment, together with autologous product manufacturing hurdles, which hinder timely delivery of treatment to the patient. Also, most current CAR T therapies are viral based, limiting the ability to administer repeated, longer-term treatments. MaxCyte has developed its first CAR product, MCY-M11, applying the CARMA™ non-viral, mRNA-based platform for rapid (less than 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 and relevant therapeutic target because of its high differential expression in many solid tumors with only low levels of expression in mesothelial cells of mostly non-critical normal tissues. The transient expression of the CAR transgene may be important in limiting potential excessive or unwanted toxicity, while allowing for multiple therapeutic infusions needed to trigger a potent and more effective host immune response. In an in vivo murine model, MCY-M11 cells were shown to have 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 phase 1 study of MCY-M11 in patients with advanced ovarian cancer and peritoneal mesothelioma (NCT03608618) is described here.
Methods: A standard 3+3 design phase 1 study exploring 4 ascending cell dose levels, in patients with relapsed/refractory adenocarcinoma of the ovary, fallopian tube, primary peritoneum, or peritoneal mesothelioma. A minimum of 15 patients will be enrolled to receive one cycle of 3 weekly doses (D1, D8, D15) of MCY-M11 administered intraperitoneally. The primary objective is to characterize safety (Incidence and severity of adverse events assessed per NCI CTCAE v5.0), tolerability, and feasibility of infusion of MCY-M11. Secondary objectives include assessment of antitumor activity (RECIST, irRECIST, and serum biomarkers), and correlates of CAR performance and immune activation. The study is being conducted at two centers, and the first patient was dosed in October 2018. Recruitment in dose level 1 cohort continues.
Citation Format: Armin Ghobadi, Premal Thaker, David Weng, Julie Vanas, Irene Ekwede, Mira Pavlova, Robert Keefe, Michael Kuo, Claudio Dansky Ullmann, Raffit Hassan, Christina Annunziata. A phase 1 study of intraperitoneal MCY-M11 therapy for women with platinum resistant high grade serous adenocarcinoma of the ovary, primary peritoneum, or fallopian tube, or subjects with peritoneal mesothelioma with recurrence after prior chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT159.