Phase I study of intravenous Seneca Valley virus (NTX-010), a replication competent oncolytic virus, in patients with neuroendocrine (NE) cancers

Abstract

4629 Background: NTX-010 is a naturally occurring replication competent picornavirus with potent and selective tropism for human NE tumors, including small cell cancers and carcinoid. NTX-010 elicts rapid cytolysis in vitro and durable responses following IV dosing in multiple xenograft models. Methods: A first-in-human phase I study of IV NTX-010 was conducted across 5 log-increment dose cohorts from 107 vp/kg to 1011 vp/kg, in patients with NE cancers. Study endpoints included toxicity assessment, response assessment, evaluation of viral titers and clearance in blood, sputum, nasal swabs, urine, and stool, and assessment of neutralizing antibody (Ab) development. Results: 30 patients were treated (6 small cell, 24 carcinoid-type). All small cell patients were heavily pretreated (> third line) and received 107 vp/kg. In these patients, median PFS was 1.2 months and median OS was 4.1 months, including 1 long term (16 month +) survivor with prolonged SD after progressing through prior therapies. Carcinoid patients in cohorts 1–4 have 70% SD rate and median PFS of 5.4 months (95% CI 3.6 to NE); median OS has not been reached. Cohort 5, a 12 patient expansion cohort at 1011 vp/kg restricted to carcinoid, is still being monitored and shows promising antitumor activity including improvement in carcinoid syndrome symptoms, decline in 5HIAA and other serum markers, minor responses by CT scan, and an objective PET response (>50% decrease in SUV). There were no DLTs in any cohort. Evidence of intratumoral viral replication includes delayed kinetics in serum viral titer, post-infusion serum titers greater then the dose administered and positive immunohistochemistry and/or RT-PCR signal for viral antigens in tumor mass despite Ab production. Viral clearance was documented in all subjects and correlated temporally with development of antiviral Ab. Conclusions: NTX-010 is the first picornavirus to be evaluated as an anticancer therapeutic. A single IV dose of 1011 vp/kg of NTX-010 is safe, has predictable viral kinetics, and shows promising activity against NE tumors. Phase II testing of this novel agent either as a single agent or in combination with standard cytotoxic therapies is warranted. [Table: see text]