A Phase I Study of Pembrolizumab in Combination with Enadenotucirev (enad) (SPICE) in Subjects with Metastatic or Advanced Carcinoma.

TPS3112 Background: EnAd is a tumor-selective chimeric Ad11/Ad3 group B oncolytic adenovirus developed using a process of directed evolution. Phase I clinical studies have identified a well-tolerated dose and regimen for EnAd monotherapy. EnAd shows a high level of selective replication and cell killing for a broad range of carcinoma cell lines with little replication in normal and non-carcinoma cells. Woller et al. have shown that an oncolytic virus can stimulate immune cell activity and that this stimulation can synergize with checkpoint inhibitor (CPI) activity and can reverse CPI resistance. This emerging data supports the rationale for the combination study of EnAd with CPI, pembrolizumab (anti-PD-1 antibody). SPICE is a phase I multi-center, open label, nonrandomized clinical study in subjects with metastatic or advanced carcinoma. The study design allows for an initial dose escalation stage, followed by a dose expansion stage which will include treatment of tumors normally non-responsive to CPI. Methods: In the initial dose escalation phase, 3 cohorts of patients with metastatic or advanced colorectal, urothelial, squamous cell head and neck and salivary gland carcinomas are administered intravenously an increasing dose of enadenotucirev and pembrolizumab in a standard