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
5043 - Comprehensive results of a Phase Ib study with a HER2/neu B-cell peptide vaccine administered with cisplatin and 5-fluorouracil or capecitabine chemotherapy show safety, immunogenicity and clinical response in patients with HER2/Neu overexpressing advanced gastric cancer
Presenter: Ursula Wiedermann
Session: Poster Display session 3
Resources:
Abstract
4506 - Single intravenous preoperative administration of the oncolytic virus Pexa-Vec to prime anti-tumor immunity
Presenter: Adel Samson
Session: Poster Display session 3
Resources:
Abstract
1631 - Randomized phase 2 clinical trial of NY-ESO-1 protein vaccine combined with cholesteryl pullulan (CHP-NY-ESO-1) in resected esophageal cancer patients
Presenter: Shinichi Kageyama
Session: Poster Display session 3
Resources:
Abstract
4244 - T cell repertoire sequencing reveals dynamics of response to dendritic cell vaccine plus dasatinib for checkpoint blockade resistant metastatic melanoma
Presenter: Luca Quagliata
Session: Poster Display session 3
Resources:
Abstract
5791 - Ixovex, a novel oncolytic E1B-mutated adenovirus
Presenter: Mohiemen Anwar
Session: Poster Display session 3
Resources:
Abstract
4170 - Anti-CSPG4 DNA vaccination as a promising strategy for the treatment of CSPG4+ tumors: a comparative oncology trial
Presenter: Federica Riccardo
Session: Poster Display session 3
Resources:
Abstract
5780 - Antitumor activity, immunogenicity and safety of a novel PD-1 vaccine in combination with two chimeric HER-2 peptide vaccine in syngeneic Balb/c, C57Bl/6 models and in beagle dogs
Presenter: Pravin Kaumaya
Session: Poster Display session 3
Resources:
Abstract
5860 - Maternal immunization against ALK as a weapon to fight neuroblastoma
Presenter: Giuseppina Barutello
Session: Poster Display session 3
Resources:
Abstract
4720 - Phase 1 study evaluating safety, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of ABBV-428, first-in-class mesothelin (MSLN)-CD40 bispecific, in patients (pts) with advanced solid tumors
Presenter: Jason Luke
Session: Poster Display session 3
Resources:
Abstract
5717 - Anti-PD-L1/IL-15 fusion protein generates robust adaptive immune gene signatures in tumors leading to tumor inhibition and memory responses
Presenter: Stella Martomo
Session: Poster Display session 3
Resources:
Abstract