MEM-288 / Memgen, Moffitt Cancer Center - LARVOL DELTA

MEM-288 Oncolytic Virus Alone and in Combination With Standard of Care Therapy in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Memgen, Inc. | N=61 ➔ 40 | Trial completion date: Nov 2026 ➔ Dec 2031 | Trial primary completion date: Nov 2025 ➔ Feb 2027

Enrollment change • Trial completion date • Trial primary completion date • Breast Cancer • Head and Neck Cancer • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Melanoma • Merkel Cell Carcinoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • Triple Negative Breast Cancer • ALK • BRAF • EGFR • KRAS • ROS1

Oncolytic adenovirus MEM-288 encoding membrane-stable CD40L and IFNβ induces an anti-tumor immune response in high grade serous ovarian cancer. (PubMed, Neoplasia) - "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."

IO biomarker • Journal • Oncolytic virus • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • CD40LG • IFNB1

Moffitt Initiates Groundbreaking Clinical Trial with Oncolytic Virus for Non-Small Cell Lung Cancer (Newswise) - P1a | N=61 | NCT05076760 | Sponsor: Memgen, Inc. | "Spearheaded by Moffitt, in collaboration with Duke Cancer Institute, the trial follows the successful completion of a first-in-human phase 1a trial of MEM-288 for non-small cell lung cancer. The phase 1a trial demonstrated that MEM-288 safely shrank tumors and enhanced antitumor immunity in patients...The recent phase 1a trial demonstrated promising results, with MEM-288 increasing both the density and efficacy of tumor-killing T cells. Importantly, it also enhanced systemic antitumor T cells capable of targeting metastatic sites beyond the injected tumors...This trial’s significance is underscored by a recent R01 grant (R01CA283730) awarded to Beg by the National Cancer Institute. The $2.3 million five-year grant....will support further research into MEM-288."

Enrollment closed • Financing • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Oncolytic adenovirus dually expressing interferon beta and membrane-stable CD40 ligand increases polyfunctional CD8+T cells associated with antitumor activity (AACR 2024) - P1 | "The robust polyfunctional CD8+ T cell response in these studies is consistent with T cell-driven antitumor activity found in both our preclinical tumor experiments and our clinical studies in advanced NSCLC patients responding to MEM-288. Overall, our findings suggest MEM40 + IFNβ generates a strong polyfunctional CD8+ T cell response in the TME that warrants continued evaluation to understand the pleiotropic mechanisms of this cancer immunotherapy."

IO biomarker • Oncolytic virus • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD40LG • CD8 • GZMB • IFNB1 • IFNG • PRF1 • PTPRC • TNFA

MEM-288 Oncolytic Virus Alone and in Combination With Nivolumab in Solid Tumors Including Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=61 | Recruiting | Sponsor: Memgen, Inc.

Combination therapy • IO biomarker • Oncolytic virus • Trial completion date • Trial primary completion date • Breast Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hepatology • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Melanoma • Merkel Cell Carcinoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • Triple Negative Breast Cancer • ALK • BRAF • EGFR • KRAS • ROS1

MEM-288 Oncolytic Virus Alone and in Combination With Nivolumab in Solid Tumors Including Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=61 | Recruiting | Sponsor: Memgen, Inc. | N=18 ➔ 61

Enrollment change • Breast Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hepatology • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Melanoma • Merkel Cell Carcinoma • Non Small Cell Lung Cancer • Non-melanoma Skin Cancer • Oncology • Pancreatic Cancer • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • Triple Negative Breast Cancer • ALK • BRAF • EGFR • KRAS • ROS1

The anti-tumor activity of IFNβ and membrane-stable CD40L expressing oncolytic virus MEM-288 in NSCLC patients is associated with modulation of the tumor microenvironment and systemic immune response (SITC 2023) - P1 | "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."

Biomarker • Clinical • IO biomarker • Oncolytic virus • Tumor microenvironment • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD40LG • IFNB1 • IFNG

A phase 1 first-in-human study of interferon beta (IFNβ) and membrane-stable CD40L expressing oncolytic virus (MEM-288) in solid tumors including non–small-cell lung cancer (NSCLC). (ASCO 2023) - P1 | "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."

IO biomarker • Oncolytic virus • P1 data • Gastrointestinal Cancer • Hepatology • Immune Modulation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CD40LG • CD8 • IFNB1 • IFNG

Memgen Announces New Clinical Data on MEM-288 in Advanced/Metastatic NSCLC at ASCO 2023 Annual Meeting (Businesswire) - P1 | N=18 | NCT05076760 | Sponsor: Memgen, Inc. | "Memgen...announced updated clinical data from its first-in-human study of MEM-288, an oncolytic viral therapy, in patients with advanced/metastatic refractory non-small cell lung cancer...at the...ASCO 2023 Annual Meeting....This MEM-288 dose-escalation, monotherapy study has now completed patient accrual of fourteen patients with advanced/metastatic non-small cell lung cancer (NSCLC) refractory to standard therapies including anti-PD(L)1. The study’s primary safety endpoint was achieved with no dose limiting toxicities at any dose level, and no patients stopped treatment due to toxicity....Four patients had significant shrinkage (range -26% to -54%) of injected lesions, which correlated with strong remodeling of the tumor microenvironment and infiltration of CD8+ T-cells, and significant necrosis and apoptosis of tumor cells measured in tumor biopsies."

P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

A phase 1 first-in-human study of MEM-288 oncolytic virus in solid tumors including non-small cell lung cancer (NSCLC): impact on tumor and systemic T cell immunity (AACR 2023) - P1 | "Of note, a pt with strong stimulation of tumor and systemic T cell immunity after MEM-288 had a subsequent CR (ongoing >6 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. Preliminary safety, antitumor and immune response data are encouraging. Updated results and immune data will be presented. An expansion arm is planned with combination MEM-288 and anti-PD1 antibody in pts with advanced NSCLC refractory to ICI."

IO biomarker • Oncolytic virus • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD40LG • CD8 • IFNB1 • IFNG

Turning up the heat: Oncolytic virus MEM-288 induces anti-tumoral immune response in pre-clinical models of high grade serous ovarian cancer (SGO 2023) - No abstract available

Oncolytic virus • Preclinical • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor

Impact of intralesional oncolytic viral therapy targeting in situ activation of CD40 and type 1 interferon signaling pathways on the TME and systemic T cell immunity in murine models and cancer patients (SITC 2022) - P1 | "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."

IO biomarker • Oncolytic virus • Preclinical • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD40 • CD40LG • CD8 • GZMB • IFNB1

Combination IFNβ and membrane-stable CD40L maximize tumor dendritic cell activation and lymph node trafficking to elicit systemic T-cell immunity. (PubMed, Cancer Immunol Res) - "Oncolytic viral therapies induce direct killing of tumor cells and activation of conventional dendritic cells (cDCs); however, cDC activation has not been optimized with current therapies. 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."

IO biomarker • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD40LG • CD8 • IFNB1

Memgen Reports Results From Its First-In-Human Clinical Trial of MEM-288 in Solid Tumors Refractory to Checkpoint Inhibitors at SITC 2022 (Businesswire) - P1 | N=18 | NCT05076760 | Sponsor: Memgen, Inc. | "Memgen...presented the first clinical data for MEM-288, its oncolytic viral therapy, at the Society for Immunotherapy of Cancer (SITC) 37th Annual Meeting....The interim results from this ongoing first-in-human Phase 1 trial indicate that MEM-288 is well tolerated and expands tumor-fighting T cells. Seven patients with solid tumors received at least one intratumoral injection of MEM-288 with no dose-limiting toxicity or discontinuation due to toxicity. The only reported adverse event in more than one patient was grade 1 injection site tenderness. The 7 patients included 6 with non-small cell lung cancer (NSCLC) and 1 with pancreatic cancer. All 6 NSCLC patients had already received 2 to 4 lines of therapy including one or more lines with checkpoint inhibitors before enrollment."

P1 data • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Thoracic Cancer

ONCOLYTIC ADENOVIRUS MEM-288 ENCODING MEMBRANE-STABLE CD40L AND IFN BETA INDUCES AN ANTI-TUMOR IMMUNE RESPONSE IN A HIGH GRADE SEROUS OVARIAN CANCER MOUSE MODEL (IGCS 2022) - "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."

IO biomarker • Oncolytic virus • Preclinical • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • CD40LG • CD8 • IFNB1 • IFNG

Oncolytic adenovirus encoding transgenes for IFN-beta and recombinant CD40 ligand promotes conventional dendritic cell activation and trafficking with enhanced tumor infiltrating lymphocytes for effective cancer immunotherapy (AACR 2022) - "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."

IO biomarker • Oncolytic virus • Lung Cancer • Oncology • Solid Tumor • CCR7 • CD40LG • CD8 • CD86 • IFNAR1 • IFNB1

Study of MEM-288 Oncolytic Virus in Solid Tumors Including Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: Memgen, Inc. | Not yet recruiting ➔ Recruiting | Initiation date: Nov 2021 ➔ Feb 2022

Enrollment open • Oncolytic virus • Trial initiation date • Breast Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hepatology • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Melanoma • Merkel Cell Carcinoma • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Non-melanoma Skin Cancer • Oncology • Pancreatic Cancer • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • Triple Negative Breast Cancer • ALK • BRAF • EGFR • KRAS • ROS1

Memgen Announces FDA Clearance of IND Application for MEM-288 (Businesswire) - “MEM-288 to be studied in patients with cancers not responding to checkpoint inhibitors including non-small cell lung cancer and triple-negative breast cancer. Initiation of patient screening in Phase 1 study of MEM-288 expected by 12/31/2021. Memgen, Inc....announced that the U.S. Food and Drug Administration (FDA) has accepted its investigational new drug (IND) application for MEM-288, the company’s wholly-owned cancer immunotherapy candidate for the treatment of multiple solid tumors.”

FDA event • New P1 trial • Breast Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Merkel Cell Carcinoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Triple Negative Breast Cancer

Study of MEM-288 Oncolytic Virus in Solid Tumors Including Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P1; N=18; Not yet recruiting; Sponsor: Memgen, Inc.

New P1 trial • Oncolytic virus • Breast Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hepatology • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Melanoma • Merkel Cell Carcinoma • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Non-melanoma Skin Cancer • Oncology • Pancreatic Cancer • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • Triple Negative Breast Cancer • ALK • BRAF • EGFR • KRAS • ROS1

[VIRTUAL] Defining anti-tumor immune stimulatory mechanisms of MEM-288, a CD40 ligand and IFN-beta dual-transgene armed oncolytic adenovirus (AACR 2021) - "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."

IO biomarker • Oncolytic virus • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD40LG • CD8 • CD86 • IFNAR1

[VIRTUAL] Development of MEM-288, a dual-transgene armed and conditionally replication-enhanced oncolytic adenovirus with potent systemic antitumor immunity (AACR-II 2020) - "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."

IO Biomarker • Oncolytic Virus • Lung Cancer • Melanoma • Oncology • Solid Tumor • Thoracic Cancer • CD40LG • PD-1