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
4900 - Molecular profiling and prognostic significance of TP53 mutations in Diffuse Large B Cell Lymphoma: identifying a high-risk subgroup
Presenter: Yuan-Kai Shi
Session: Poster Display session 3
Resources:
Abstract
3809 - Differential expression of various miRNAs in Pediatric Cytogenetically Normal Acute Myeloid Leukemia (CN-AML)
Presenter: Vikas Gaur
Session: Poster Display session 3
Resources:
Abstract
4750 - Circulating tumour cells in head and neck and non-small cell lung cancer
Presenter: Kenneth O'Byrne
Session: Poster Display session 3
Resources:
Abstract
3704 - OX40/OX40L protein expression in Non-small cell lung cancer and its role in clinical outcome and relationships with other immune biomarkers
Presenter: Xiaoshen Zhang
Session: Poster Display session 3
Resources:
Abstract
2235 - Effect of Serum Survivin on Survival among Non-Small Cell Lung Cancer Patients; NCI Experience
Presenter: Reham Rashed
Session: Poster Display session 3
Resources:
Abstract
2788 - Enhanced performance of prognostic estimation from TCGA RNAseq data using transfer learning.
Presenter: Helene Vanacker
Session: Poster Display session 3
Resources:
Abstract
4689 - Analysis of Circulating Tumor DNA for Early Relapse Detection in Stage III Colorectal Cancer After Adjuvant Chemotherapy
Presenter: Samuel Jacobs
Session: Poster Display session 3
Resources:
Abstract
1454 - Ascites-derived circulating microRNAs as potential diagnostic biomarkers of gastric cancer-associated malignant ascites
Presenter: Hye Sook Han
Session: Poster Display session 3
Resources:
Abstract
5574 - Results from TRIO030, a Pre-Surgical Tissue-Acquisition Study to Evaluate Molecular Alterations in Human Breast Cancer Tissue Following Short-Term Exposure to the Androgen Receptor Antagonist Darolutamide
Presenter: Hsiao-Wang Chen
Session: Poster Display session 3
Resources:
Abstract
1787 - JMJD2A is a novel epigenetic factor of chemotherapeutic susceptibility in gastric cancer
Presenter: Yasushi Sato
Session: Poster Display session 3
Resources:
Abstract