Academic Journal
Phase I Study of Oncolytic Virus VV1 as Monotherapy or in Combination with Avelumab in Patients with Relapsed Refractory Solid Tumors.
| Title: | Phase I Study of Oncolytic Virus VV1 as Monotherapy or in Combination with Avelumab in Patients with Relapsed Refractory Solid Tumors. |
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| Authors: | Merchan JR; University of Miami, Miami, Florida., Patel MR; University of Minnesota , Minneapolis, Minnesota., Cripe TP; Nationwide Children's Hospital , Columbus, Ohio., Old MO; Ohio State University, Columbus, Ohio., Boughton J; Vyriad, Rochester, Minnesota., Diaz RM; Vyriad, Rochester, Minnesota., Peng KW; Vyriad, Rochester, Minnesota.; Mayo Clinic , Rochester, Minnesota., Russell SJ; Vyriad, Rochester, Minnesota.; Mayo Clinic , Rochester, Minnesota., Russell L; Vyriad, Rochester, Minnesota., Packiriswamy N; Vyriad, Rochester, Minnesota., Wiegert E; Bexon Clinical Consulting LLC, Montclair, New Jersey., Bexon AS; Bexon Clinical Consulting LLC, Montclair, New Jersey., Powell SF; Sanford Health, Sioux Falls, South Dakota. |
| Source: | Cancer research communications [Cancer Res Commun] 2026 Aug 01; Vol. 6 (8), pp. 1862-1874. |
| Publication Type: | Journal Article; Clinical Trial, Phase I; Multicenter Study |
| Language: | English |
| Journal Info: | Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 9918281580506676 Publication Model: Print Cited Medium: Internet ISSN: 2767-9764 (Electronic) Linking ISSN: 27679764 NLM ISO Abbreviation: Cancer Res Commun Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Philadelphia, Pennsylvania] : American Association for Cancer Research, [2021]- |
| MeSH Terms: | Antibodies, Monoclonal, Humanized*/administration & dosage , Antibodies, Monoclonal, Humanized*/therapeutic use , Antibodies, Monoclonal, Humanized*/adverse effects , Neoplasms*/therapy , Neoplasms*/pathology , Neoplasms*/immunology , Oncolytic Viruses*/genetics , Oncolytic Virotherapy*/methods , Oncolytic Virotherapy*/adverse effects , Neoplasm Recurrence, Local*/therapy , Antineoplastic Agents, Immunological*/therapeutic use, Humans ; Female ; Male ; Middle Aged ; Aged ; Adult ; Combined Modality Therapy |
| Abstract: | 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. (©2026 American Association for Cancer Research.) |
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| Grant Information: | Vyriad (Vyriad Inc.) |
| Substance Nomenclature: | 0 (Antibodies, Monoclonal, Humanized) KXG2PJ551I (avelumab) 0 (Antineoplastic Agents, Immunological) |
| Entry Date(s): | Date Created: 20260622 Date Completed: 20260805 Latest Revision: 20260923 |
| Update Code: | 20260923 |
| PubMed Central ID: | PMC13440224 |
| DOI: | 10.1158/2767-9764.CRC-25-0803 |
| PMID: | 42330318 |
| Database: | MEDLINE |
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