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
2600 - Atezolizumab (atezo) vs chemotherapy (chemo) in patients (pts) with platinum-treated locally advanced or metastatic urothelial carcinoma (mUC): a long-term overall survival (OS) and safety update from the Phase III IMvigor211 study
Presenter: Michiel Van der Heijden
Session: Poster Display session 3
Resources:
Abstract
3598 - Three-Year Follow-Up From the Phase 3 KEYNOTE-045 Trial: Pembrolizumab (Pembro) Versus Investigator’s Choice (Paclitaxel, Docetaxel, or Vinflunine) in Recurrent, Advanced Urothelial Cancer (UC)
Presenter: Andrea Necchi
Session: Poster Display session 3
Resources:
Abstract
2382 - First Report of Efficacy and Safety From a Phase 2 Trial of Tislelizumab, an Anti-PD-1 Antibody, for the Treatment of PD-L1+ Locally Advanced or Metastatic Urothelial Carcinoma (UC) in Asian Patients
Presenter: Dingwei Ye
Session: Poster Display session 3
Resources:
Abstract
2388 - Quality of Life of Metastatic Urothelial Cancer (mUC) Patients Treated with Enfortumab Vedotin (EV) Following Platinum-Containing Chemotherapy and a Checkpoint Inhibitor (CPI): Data from EV-201 Cohort 1
Presenter: Bradley McGregor
Session: Poster Display session 3
Resources:
Abstract
3748 - Safety and efficacy of atezolizumab (atezo) in patients (pts) with autoimmune disease (AID): subgroup analysis of the SAUL study in locally advanced/metastatic urinary tract carcinoma
Presenter: Yohann Loriot
Session: Poster Display session 3
Resources:
Abstract
1126 - Validation of the VIO prognostic index in patients with metastatic urothelial carcinoma treated with immune-checkpoint inhibitors
Presenter: Rafael Morales Barrera
Session: Poster Display session 3
Resources:
Abstract
3693 - Pathologic outcomes after neoadjuvant chemotherapy for high-risk muscle invasive bladder cancer
Presenter: Justin Matulay
Session: Poster Display session 3
Resources:
Abstract
4840 - Analysis of response to prior therapies and therapies after treatment with erdafitinib in fibroblast growth factor receptor (FGFR)-positive patients (pts) with metastatic urothelial carcinoma (mUC)
Presenter: Arlene Siefker-Radtke
Session: Poster Display session 3
Resources:
Abstract
1221 - Clinical outcomes by sex with atezolizumab (atezo) monotherapy in patients (pts) with locally advanced/metastatic urothelial carcinoma (mUC)
Presenter: Jean Hoffman-censits
Session: Poster Display session 3
Resources:
Abstract
1715 - National Small Cell Bladder Cancer Audit: Results from 26 UK institutions
Presenter: Caroline Chau
Session: Poster Display session 3
Resources:
Abstract