Abstract LB-B002: A phase 1 trial of the oncolytic virus SVV-001 with Nivolumab and Ipilimumab in patients with high grade Neuroendocrine Neoplasms

High-grade neuroendocrine neoplasms (NENs), including poorly differentiated neuroendocrine carcinomas (NECs) and well-differentiated grade 3 neuroendocrine tumors (NETs), are aggressive malignancies with limited effective treatment options. Immune checkpoint inhibitors (ICIs) have demonstrated limited clinical activity in these neoplasms. Seneca Valley Virus (SVV-001) is a novel oncolytic RNA virus that has shown synergistic activity with ICIs in preclinical cancer models. Additionally, SVV-001 has been observed to reverse ICI resistance in vivo, further supporting its evaluation in combination with nivolumab and ipilimumab. This is an investigator-initiated, phase 1, dose-escalation and cohort-expansion study evaluating intratumoral SVV-001 in combination with nivolumab and ipilimumab in patients with histologically confirmed poorly differentiated NEC or well-differentiated grade 3 NET. The trial was activated in March 2025, with patient enrollment currently ongoing. A standard 3+3 dose-escalation design is being employed to determine the recommended phase 2 dose (RP2D). Following dose escalation, an expansion cohort will further evaluate safety and preliminary signals of activity. Tumor endothelial marker 8 (TEM8), a potential biomarker of SVV-001 sensitivity, will be assessed as part of correlative studies. Hereby we present the interim safety and the first efficacy results from dose escalation cohorts. As of January 12, 2026, the trial has completed enrolling patients in first two cohorts – dose level 1 (DL1) and dose level 2, and 2 patients in dose level 3 (DL3) cohort. All 9 enrolled patients received one dose of SVV-001 in combination with ipilimumab and nivolumab per protocol. No DLTs were observed in DL1 and DL2. Overall two patients experienced Grade 3 serious adverse events (anorexia, weight loss; hyperbilirubinemia, increase of alanine amino transferase; and seizures) unrelated to SVV-001, and one patient reported Grade 3 adverse event (elevated creatinine, xerostomia) possibly related to SVV-001 injection. Two patients achieved a partial response, 2 had stable disease and 3 came off study due to disease progression. Updated safety and efficacy data will be presented at symposium. The interim data demonstrate an acceptable safety profile and encouraging signs of efficacy in a disease representing a significant unmet medical need. NCT06889493 Aman Chauhan, Isildinha M. Reis, Chinmay Jani, Rakhi Modak, Daniel Bilbao. Cortes, Stephanie Baboun, Alexander Rivera, Hung Trinh, Paul Hallenbeck, Jaime Merchan, Gilberto Lopes, Peter Hosein. A phase 1 trial of the oncolytic virus SVV-001 with Nivolumab and Ipilimumab in patients with high grade Neuroendocrine Neoplasms [abstract]. In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr LB-B002.