Abstract Background: 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. Methods: 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. Results: 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. Conclusion: The interim data demonstrate an acceptable safety profile and encouraging signs of efficacy in a disease representing a significant unmet medical need. Clinical Trial Identifier: NCT06889493 Citation Format: 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.
Chauhan et al. (Thu,) studied this question.