1308TiP - A phase I study of intraperitoneal MCY-M11 Anti-mesothelin CAR 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

BackgroundChimeric 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 (<1day) 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 designThis 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 identificationNCT03608618. Legal entity responsible for the studyMaxCyte Inc. FundingMaxCyte Inc. DisclosureC. 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.