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Updated: Jun 24, 2026
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Phase I Study of Oncolytic Virus VV1 as Monotherapy or in Combination with Avelumab in Patients with Relapsed
Jaime R Merchan1, Manish R Patel2, Timothy P Cripe3
1University of Miami, Miami, Florida.
Purpose:
VV1 is designed to induce selective oncolysis of tumor cells and amplify cellular antitumor immune responses. This open-label, phase I, multicenter clinical trial assessed the safety and tolerability of VV1 monotherapy administered intratumorally or intravenously or administered intravenously in combination with avelumab.
Patients And Methods:
Patients with advanced solid tumors received intratumoral (n = 27) or intravenous VV1 monotherapy (n = 33) or intravenous VV1 plus avelumab (n = 16). Infusion durations (15-180 minutes) and viral dose (1.7 × 1010 or 1 × 1011 TCID50) were also evaluated. Study objectives included VV1 safety and tolerability, pharmacokinetics, pharmacodynamics, preliminary efficacy, and immune responses.
Results:
Intratumoral and intravenous VV1 were well tolerated, and injection reactions were infrequent. The most common adverse events of any grade related to VV1 were cytokine release syndrome (58%), fatigue (33%), and decreased lymphocyte count (32%). Virus infection of tumors was confirmed by NIS imaging and increases in serum levels of virally encoded interferon-β (IFNβ). Histologic tumor analysis at 28 days after intratumoral VV1 administration indicated increases in tumor-infiltrating immune cells. Two durable partial responses were recorded: a patient with pheochromocytoma after one intravenous dose of VV1 and a patient with thymic cancer in the combination arm. Stable disease was observed in 17 of 49 patients (34.7%) who received intravenous VV1.
Conclusions:
This first-in-human study demonstrates that intratumoral or intravenous VV1 administration had an acceptable safety profile as monotherapy and intravenously in combination with avelumab. There is preliminary antitumor activity. Intratumoral VV1 plus cemiplimab is now showing promise in the neoadjuvant setting.
Significance:
VV1 is a tumor-selective oncolytic vesicular stomatitis virus engineered to express IFNβ and the thyroidal NIS reporter gene. In this phase I study, we have demonstrated that a single administration of VV1, as a monotherapy or with an immune checkpoint inhibitor is safe, infects tumor lesions resulting in intratumoral infiltration of immune cells, and exhibits early signs of antitumor activity in patients with advanced unresectable and metastatic solid tumors.
Insights
VV1, an oncolytic virus, showed an acceptable safety profile in a phase 1 trial for advanced solid tumors. Preliminary antitumor activity was observed, with promising results in combination therapies.
Area of Science:
- Oncology
- Immunotherapy
- Virology
Background:
- Oncolytic viruses offer a dual mechanism of action: direct tumor cell lysis and stimulation of anti-tumor immune responses.
- VV1 is a novel oncolytic virus engineered for selective tumor cell targeting and immune response amplification.
Purpose of the Study:
- To assess the safety and tolerability of VV1 administered intratumorally (IT) or intravenously (IV) as monotherapy, and IV in combination with avelumab.
- To evaluate preliminary efficacy, pharmacokinetics, pharmacodynamics, and immune responses in patients with advanced solid tumors.
Main Methods:
- An open-label, phase 1, multicenter clinical trial involving patients with advanced solid tumors.
- VV1 was administered IT (n=27) or IV (n=33) as monotherapy, or IV in combination with avelumab (n=16).
- Dose and infusion duration were evaluated, alongside safety, tolerability, PK/PD, and immune markers.
Main Results:
- VV1 demonstrated an acceptable safety profile, with infrequent injection reactions. Common adverse events included cytokine release syndrome (58%), fatigue (33%), and decreased lymphocyte count (32%).
- Tumor infection by VV1 was confirmed via imaging and elevated interferon-β levels. Histological analysis showed increased tumor-infiltrating immune cells post-IT VV1.
- Preliminary efficacy included two durable partial responses and stable disease in 34.7% of patients receiving IV VV1 monotherapy.
Conclusions:
- Intratumoral or intravenous VV1 administration as monotherapy, and IV VV1 in combination with avelumab, exhibited an acceptable safety profile in this first-in-human study.
- Preliminary evidence of antitumor activity supports further investigation of VV1.
- Ongoing studies, such as IT VV1 plus cemiplimab in the neoadjuvant setting, are showing promise.
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