Abstract 2255
Background
VSV-IFNβ-NIS (Voyager V1; VV1) is a VSV-derived OV with low human seroprevalence. In addition to its tumor-selective and immune-stimulatory properties, VV1 encodes the human thyroidal sodium iodide symporter NIS to allow imaging of virus-infected tumors with IV 99mTc pertechnetate. Preclinical studies show increasing 99mTc uptake correlates with virus dose and allows spatial and temporal tracking of virus.
Methods
Single-photon emission computerized tomography (SPECT/CT) is used to assess virus replication and spread. In a phase 1 study, VV1 is given intratumorally into 1 target lesion on Day 1 (D1). SPECT/CT imaging is performed 45 minutes after 20 mCi IV 99mTc at baseline and D3. If there is uptake in injected tumor on D3, SPECT/CTs are also done D8 and D15. Imaging requirements include: gamma camera, low energy high resolution collimators with standard acquisition protocols and iterative image reconstruction. All images are read locally and centrally.
Results
SPECT/CT has been performed on 12 patients at 4 VV1 dose levels (DL). 99mTc uptake was not detected at the first 2 DLs but was seen in injected lesions of 2/4 pts at DL 3 (3e7 TCID50) in pts with metastatic colorectal and pancreas cancer, and 1/2 to date at DL 4. PD analysis revealed SPECT/CT-positive pts had peak uptake in injected lesions between D3 and D8. Tumor biopsy samples are being analyzed to correlate SPECT/CT with viral RNA. Spread to uninjected lesions was not yet visualized, but viral RNA was recovered in cystic fluid from the lesion with the strongest signal in a pancreas cancer pt.
Conclusions
This novel therapeutic and diagnostic approach allows PD visualization of the investigational oncolytic virotherapy, VV1, replicating within the injected lesion. Positive images at dose levels 3-4 indicate we have reached a viral dose that allows sufficient viral replication for potential clinical activity. Further objectives include correlation of SPECT/CT positivity with clinical response, viremia, immune infiltrates, and genetic markers of susceptibility to OV therapy.
Clinical trial identification
NCT02923466.
Legal entity responsible for the study
Vyriad.
Funding
Vyriad.
Editorial Acknowledgement
Disclosure
R.M. Diaz: Paid consultant running the trial: Vyriad. S.J. Russell: CEO and own equity: Vyriad. A.S. Bexon: Paid consultant and CMO: Vyriad. K.W. Peng: CTO and own equity: Vyriad. All other authors have declared no conflicts of interest.