MEM-288 Oncolytic Virus Alone and in Combination With Nivolumab in Solid Tumors Including Non-Small Cell Lung Cancer

Pancreatic Cancer Clinical Trial

Official title: Phase I Study of MEM-288 Oncolytic Virus Alone and in Combination With Nivolumab in Solid Tumors Including Non-Small Cell Lung Cancer (NSCLC)

Status Recruiting

Clinical Trial Summary

This phase I trial is designed in two parts. First as an open-label, dose escalation trial of MEM-288 monotherapy in which investigators aim to find the maximum tolerated dose (MTD) and recommended phase II dose (RP2D). Subjects with selected solid tumors including non-small cell lung cancer (NSCLC) who have a tumor lesion which is accessible for injection will undergo intratumoral injection of MEM-288. Following completion of the monotherapy study portion of the study, an expansion arm is designed to test MEM-288 with concurrent anti-PD-1 (nivolumab) therapy for patients with first relapsed or refractory advanced/metastatic NSCLC following front-line anti-PD-1/PD-L1 with or without concurrent chemotherapy. The study rationale is that the oncolytic effect of MEM-288 combined with the presence of CD40L and type 1 interferon (IFN) in injected tumors will provide a strong signal for dendritic cell (DC)-mediated T cell activation leading to generation of systemic anti-tumor T cell responses with broad specificity akin to what is observed in the abscopal effect. Further study rationale is the anti-tumor effect of MEM-288 will be enhanced by nivolumab by reversing T cell exhaustion.

Clinical Trial Description

MEM-288 is a conditionally replicative oncolytic adenovirus vector encoding transgenes for human interferon beta (IFNβ) and a recombinant chimeric form of CD40-ligand (MEM40). MEM-288 was developed as an immunotherapy for cancer and was engineered to selectively replicate in cancer cells leading to cancer cell lysis but not cytotoxicity towards normal cells. Simultaneously, MEM-288 is designed to stimulate an anti-tumor immune response through expression of its encoded immune agonist transgenes. MEM-288 is designed to provide both antitumor activity as a standalone monotherapy and in combination with immune checkpoint inhibitor(s) to enhance the efficacy of immune checkpoint inhibition in solid tumors.

This phase I trial will be conducted in two parts. The first part is an open-label, dose escalation trial of MEM-288 monotherapy in which investigators aim to find the MTD and recommended phase II dose for the planned combination of MEM-288 with an immune checkpoint inhibitor. Patients (≥ 18 years old) eligible for study enrollment include those with either advanced/metastatic NSCLC, cutaneous squamous-cell carcinoma (cSCC), Merkel cell, melanoma, triple negative breast cancer (TNBC), pancreatic cancer, or head and neck cancer, who progressed following previous anti-PD-1/PD-L1 therapy, with a tumor lesion which is accessible for injection.

The primary study objective of the monotherapy dose escalation portion of the study is to determine the safety, tolerability, and maximum tolerated dose (MTD) of intratumoral administration of MEM-288 as a single agent. Secondary objectives will assess efficacy overall response rate, as well as disease control rate, progression free survival, duration of response, and anti-tumor immune responses.

The second part of the phase 1 trial is an expansion arm designed to test MEM-288 with concurrent anti-PD-1 (nivolumab) therapy for patients with first relapsed or refractory advanced/metastatic NSCLC following front-line anti-PD-1/PD-L1 with or without concurrent chemotherapy.

The primary study objective of the combination portion of the study is to determine the overall response rate of the combination of MEM-288 plus nivolumab in patients with advanced recurrent/metastatic NSCLC. Secondary objectives will assess the safety and tolerability of MEM-288 plus nivolumab, as well as disease control rate, progression free survival, duration of response, and anti-tumor immune responses.

MEM-288 will be administered via intratumoral injection once every 3 weeks (planned 2 doses, maximum 6 doses) at an assigned dose cohort level (from 1x10^10 to 1x10^11 viral particles) for the monotherapy portion of the study.

For the combination portion of the study, MEM-288 will be administered via intratumoral injection once every 3 weeks (planned 2 doses, maximum 6 doses) at an assigned dose total dose of 1x10^11 viral particles. MEM-288 may be injected in multiple lesions until the maximum injection dose (1x10^11 viral particles) is reached. Nivolumab will be administered at a dose of 360 mg via intravenous infusion once every 3 weeks, with optional maintenance nivolumab therapy every 3 weeks for up to 2 years. ;

Related Conditions & MeSH terms

• Advanced Cancer
• Carcinoma
• Carcinoma, Merkel Cell
• Carcinoma, Non-Small-Cell Lung
• Cutaneous Squamous Cell Carcinoma
• Head and Neck Cancer
• Lung Neoplasms
• Melanoma
• Merkel Cell Carcinoma
• Metastatic Cancer
• Non Small Cell Lung Cancer
• Pancreatic Cancer
• Solid Tumor
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

• NCT number: NCT05076760
• Study type: Interventional
• Source: Memgen, Inc.
• Contact: Mark J. Cantwell, PhD
• Phone: 858-869-1477
• Email: mcantwell@memgenbio.com
• Status: Recruiting
• Phase: Phase 1
• Start date: February 23, 2022
• Completion date: November 2026