MEM-288 Oncolytic Virus Alone and in Combination With Standard of Care Therapy in Advanced Solid Tumors

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 other agents to enhance the efficacy of immune checkpoint inhibition or chemotherapy. This phase I trial is conducted in multiple 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. Part 1A has completed and is closed to enrollment. 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. Following completion of Part 1A, there are multiple dose expansion arms designed to test MEM-288 with concurrent therapies 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 the safety and tolerability of MEM-288 in combination with either nivolumab (Part 1B) or docetaxel (Part 1C). 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 Part 1A . For study Parts 1B and 1C, 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. For Part 1B, 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. For Part 1C, patients with advanced NSCLC will be randomized to receive either an initial priming dose of MEM-288 injected into an accessible lesion (s) alone (Day 1) followed by MEM-288 in combination with standard of care docetaxel every 3 weeks up to 6 doses or MEM-288 injected into an accessible lesion(s) in combination with standard of care docetaxel therapy Day 1 and every 3 weeks up to 6 doses.