Related Experiment Video
Updated: Jun 4, 2026
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Phase I clinical study of Seneca Valley Virus (SVV-001), a replication-competent picornavirus, in advanced solid
Charles M Rudin1, John T Poirier, Neil N Senzer
1Johns Hopkins University, Baltimore, Maryland, USA. rudin@jhmi.edu
Purpose:
Seneca Valley Virus (SVV-001) is a novel naturally occurring replication-competent picornavirus with potent and selective tropism for neuroendocrine cancer cell types, including small cell lung cancer. We conducted a first-in-human, first-in-class phase I clinical trial of this agent in patients with cancers with neuroendocrine features, including small cell lung cancer.
Experimental Design:
Clinical evaluation of single intravenous doses in patients with cancers with neuroendocrine features was performed across five log-increments from 10(7) to 10(11) vp/kg. Toxicity, viral titers and clearance, neutralizing antibody development, and tumor response were assessed.
Results:
A total of 30 patients were treated with SVV-001, including six with small cell carcinoma at the lowest dose of 10(7) vp/kg. SVV-001 was well tolerated, with no dose-limiting toxicities observed in any dose cohort. Viral clearance was documented in all subjects and correlated temporally with development of antiviral antibodies. Evidence of in vivo intratumoral viral replication was observed among patients with small cell carcinoma, with peak viral titers estimated to be >10(3)-fold higher than the administered dose. One patient with previously progressive chemorefractory small cell lung cancer remained progression-free for 10 months after SVV-001 administration, and is alive over 3 years after treatment.
Conclusions:
Intravenous SVV-001 administration in patients is well tolerated at doses up to 10(11) vp/kg, with predictable viral clearance kinetics, intratumoral viral replication, and evidence of antitumor activity in patients with small cell lung cancer. Phase II clinical evaluation in small cell lung cancer is warranted, and has been initiated.
Insights
Seneca Valley Virus (SVV-001) shows promise as a novel cancer therapy. This phase I trial found SVV-001 well-tolerated in patients with neuroendocrine cancers, demonstrating intratumoral replication and antitumor activity in small cell lung cancer.
Area of Science:
- Oncology
- Virology
- Immunology
Background:
- Seneca Valley Virus (SVV-001) is a novel, replication-competent picornavirus.
- SVV-001 exhibits selective tropism for neuroendocrine cancer cells, including small cell lung cancer (SCLC).
Purpose of the Study:
- To evaluate the safety and tolerability of SVV-001 in a first-in-human, phase I clinical trial.
- To assess viral activity and preliminary antitumor effects in patients with neuroendocrine cancers, including SCLC.
Main Methods:
- Intravenous administration of single doses of SVV-001 across a range of 10(7) to 10(11) viral particles (vp)/kg.
- Assessment of toxicity, viral titers, viral clearance, neutralizing antibody development, and tumor response.
Main Results:
- SVV-001 was well-tolerated up to 10(11) vp/kg, with no dose-limiting toxicities observed.
- Intratumoral viral replication was confirmed in SCLC patients, with viral titers exceeding administered doses.
- One patient with refractory SCLC achieved 10 months of progression-free survival and remains alive over 3 years post-treatment.
Conclusions:
- Intravenous SVV-001 is safe and well-tolerated in patients with neuroendocrine cancers.
- The virus demonstrates predictable clearance, intratumoral replication, and antitumor activity in SCLC.
- Phase II trials of SVV-001 in SCLC are warranted and have commenced.
Related Concept Videos
01:03Rous Sarcoma Virus (RSV) and Cancer
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
01:03Rous Sarcoma Virus (RSV) and Cancer
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...