A Randomized Double-Blind Phase II Study of the Seneca Valley Virus (NTX-010) versus Placebo for Patients with Extensive-Stage SCLC (ES SCLC) Who Were Stable or Responding after at Least Four Cycles of Platinum-Based Chemotherapy: North Central Cancer Treatment Group (Alliance) N0923 Study

• Published in: Journal of thoracic oncology Vol. 15; no. 1; pp. 110 - 119
• Main Authors: Schenk, Erin L., Mandrekar, Sumithra J., Dy, Grace K., Aubry, Marie Christine, Tan, Angelina D., Dakhil, Shaker R., Sachs, Bradley A., Nieva, Jorge J., Bertino, Erin, Lee Hann, Christine, Schild, Steven E., Wadsworth, Troy W., Adjei, Alex A., Molina, Julian R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2020; Copyright by the International Association for the Study of Lung Cancer
• Subjects: Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carboplatin; Cisplatin - therapeutic use; Double-Blind Method; Etoposide; Humans; Lung Neoplasms - drug therapy; NTX-010; Picornaviridae; Platinum - therapeutic use; Seneca valley virus; Small cell lung cancer; Virotherapy; Small cell lung cancer; NTX-010; Seneca valley virus; Virotherapy
• ISSN: 1556-0864; 1556-1380
• DOI: 10.1016/j.jtho.2019.09.083

The Seneca Valley virus (NTX-010) is an oncolytic picornavirus with tropism for SCLC. This phase II double-blind, placebo-controlled trial evaluated NTX-010 in patients with extensive-stage (ES) SCLC after completion of first-line chemotherapy. Patients with ES SCLC who did not progress after four or more cycles of platinum-based chemotherapy were randomized 1:1 to a single dose of NTX-010 or placebo within 12 weeks of chemotherapy. The primary end point was progression-free survival (PFS). A prespecified interim analysis for futility was performed after 40 events. Viral clearance and the development of neutralizing antibodies were followed. From January 15, 2010, to January 10, 2013, a total of 50 patients were randomized and received therapy on study (26 received NTX-010 and 24 received placebo). At the specified interim analysis, the median PFS was 1.7 months (95% confidence interval [CI]: 1.4–3.1 months) for the NTX-010 group versus 1.7 months (95% CI: 1.4–4.3 months) for the placebo group (hazard ratio = 1.03, p = 0.92), and the trial was terminated owing to futility. In the NTX-010 group, PFS was shorter in patients with detectable virus at days 7 and 14 versus in those in whom it was not detected after treatment (1.0 month [95% CI: 0.4–1.5 months] versus 1.8 months [95% CI: 1.3–5.5 months, p = 0.008] and 0.9 months [95% CI: 0.4–2.6 months] versus 1.3 months [95% CI: 1.0–5.3 months], respectively [p = 0.04]). Patients with ES SCLC did not benefit from NTX-010 treatment after chemotherapy with a platinum doublet. Persistence of NTX-010 in the blood 1 or 2 weeks after treatment was associated with a shorter PFS.