MEM-288

The tumor microenvironment had a higher proportion of anti-tumor macrophages and decreased markers of angiogenesis. MEM-288 is a promising immunotherapy agent in HGSOC, with further pre-clinical studies required to understand the mechanism of action in the peritoneal microenvironment and clinical activity in combination with other therapies.

P1, N=61, Recruiting, Memgen, Inc.

P1, N=61, Recruiting, Memgen, Inc. | N=18 --> 61

05), and subsequently developed a partial response (7 months) to carboplatin/etoposide rechallenge. Although no RECIST responses were yet met, tumor shrinkage associated with an immune-active TME in the injected tumors, systemic immune response activation, and strong benefit to chemotherapy rechallenge and long-term disease control. These proof-of-concept results guided the design of an expansion study of MEM-288 with nivolumab for second-line treatment of metastatic NSCLC refractory to anti-PD(L)1 ± chemotherapy.

Of note, a pt with strong stimulation of tumor and systemic T cell immunity after MEM-288 had subsequent CR (ongoing > 7 months) to docetaxel + ramucirumab following prior treatment failure with platinum doublet + ICI received before MEM-288. Preliminary safety, antitumor and immune response data are encouraging. Updated results and immune data from this study will be presented. An expansion arm is planned with combination MEM-288 and anti-PD1 antibody in pts with advanced NSCLC refractory to ICI.

An oncolytic adenovirus (MEM-288) expressing MEM40+IFNβ in phase 1 clinical testing induced cancer cell loss concomitant with enhanced T-cell infiltration and increased systemic presence of tumor T-cell clonotypes in NSCLC patients. This approach to simultaneously target two major DC-activating pathways has potential to significantly impact the solid tumor immunotherapy landscape.

Following completion of the monotherapy study, an expansion arm is planned where MEM-288 will be combined with anti-PD1 antibody in patients with advanced NSCLC refractory to ICI. Ethics Approval The studies described received IRB approval (Moffitt: Adverra IRB, # Pro00060205, Duke: DUHS IRB, #Pro00109517) prior to commencement, and in the clinical trial described all participants gave informed consent before taking part.

MEM-288 has potent anti-tumor activity in an immune competent ovarian cancer mouse model, likely through recruitment of cytotoxic T-cells and promotion of a systemic anti-tumor T-cell response.

MEM-288 drives MEM40 + IFNβ expression in freshly resected human lung tumors and generates potent anti-tumor responses as a monotherapy and in combination with immune checkpoint inhibitors. Furthermore, MEM-288 induced enhancement of tumor-reactive TILs and provides a rationale for studies to determine whether MEM-288 pre-treatment generates a superior TIL product for more effective adoptive T cell therapy.

P1, N=18, Recruiting, Memgen, Inc. | Not yet recruiting --> Recruiting | Initiation date: Nov 2021 --> Feb 2022

P1, N=18, Not yet recruiting, Memgen, Inc.

This immune stimulatory capacity complements the additional mechanistic features of MEM-288, including enhanced tumor-specific viral replication, oncolysis, and tumor antigen release. MEM-288 is currently being prepared for first-in-human clinical testing in solid tumors as a monotherapy and in combination with ICI.

These positive preclinical data suggest MEM-288 is a potent tumor-selective oncolytic virus with desirable mechanistic features that can be ideally combined with ICI, even in the ICI refractory setting. These studies warrant clinical evaluation for lung cancer and other tumor types that are currently under development.