Dr Chauhan on Oncolytic Virus SVV-001 Plus Ipi/Nivo in Neuroendocrine Cancers

Aman Chauhan, MD, discusses a first-in-human study of intratumoral Seneca Valley virus (SVV-001) combined with ipilimumab (Yervoy) and nivolumab (Opdivo) in patients with neuroendocrine cancer. In this interview from the 2026 North American Neuroendocrine Tumor Society (NANETS) Symposium, he explains why earlier intravenous studies of this oncolytic virus failed to show benefit, and how a change in the route of administration reopened the question.

Chauhan, associate professor of medicine at the University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, notes that earlier phase 1 and phase 2 studies of the virus, including work from prolific researchers at Memorial Sloan Kettering, established tremendous safety but failed to show benefit. The reason, in his view, was delivery. When the virus was given as an intravenous infusion, the body mounted an immune response against it, generated neutralizing antibodies, and cleared it. Within 2 weeks there was essentially no active drug left, and the earlier studies administered only a single dose.

The field has since shifted toward intralesional therapy, and Chauhan describes injecting the virus directly into the tumor with the help of an interventional radiologist. That approach gives the virus an opportunity to grow, thrive, and infect the tumor instead of being neutralized in circulation.

Chauhan also points to TEM8, a biomarker identified in recent years that serves as an excellent receptor for Seneca Valley virus. Screening for TEM8-positive tumors can enhance the infectivity rate, and because TEM8-positive tumors are known to be more aggressive and carry a worse prognosis, Chauhan frames that selection strategy as addressing an unmet need rather than simply enriching for response.

The third element is combination. The study pairs SVV-001 with ipilimumab and nivolumab, agents Chauhan calls a game changer across many cancers but that have been largely ineffective in neuroendocrine disease. Of 10 patients treated with ipilimumab and nivolumab, he estimates 1 or 2 will respond, because these cancers are immunologically inert, or cold, and do not elicit an immune reaction to checkpoint inhibition. The hypothesis was whether injecting an oncolytic virus could convert cold tumors to hot ones by triggering oncolysis and the release of neoantigen. Preclinical work conducted with Seneca Therapeutics showed deep, durable responses in animal tumor models given the virus alongside PD-1 and CTLA-4 agents, with cures in many cases.

In the first-in-human study, 13 patients received a single injection of Seneca Valley virus with intravenous ipilimumab and nivolumab. That cohort cleared the safety analysis with no dose-limiting toxicity, clearing the path to part B, in which patients can receive up to 6 doses and move closer to therapeutic exposure. Even with a single dose, Chauhan reports hints of efficacy, with 2 partial responses and disease shrinkage, and 1 case that read as a partial response by RECIST but showed no visible tumor on FDG PET. He cautions that the cohort is small. The trial is open at the University of Miami and is expected to open at the University of California, San Francisco.