1338PTracking VSV-IFNβ-NIS oncolytic virus (OV) activity in patients (pts) with advanced solid tumors: The iodide symporter gene (NIS) as a pharmacodynamic (PD) marker using SPECT/CT imaging of OV therapy

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. 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.