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

Erin L Schenk, Sumithra J Mandrekar, Grace K Dy, Marie Christine Aubry, Angelina D Tan, Shaker R Dakhil, Bradley A Sachs, Jorge J Nieva, Erin Bertino, Christine Lee Hann, Steven E Schild, Troy W Wadsworth, Alex A Adjei, Julian R Molina, Erin L Schenk, Sumithra J Mandrekar, Grace K Dy, Marie Christine Aubry, Angelina D Tan, Shaker R Dakhil, Bradley A Sachs, Jorge J Nieva, Erin Bertino, Christine Lee Hann, Steven E Schild, Troy W Wadsworth, Alex A Adjei, Julian R Molina

Abstract

Introduction: 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.

Methods: 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.

Results: 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]).

Conclusions: 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.

Trial registration: ClinicalTrials.gov NCT01017601.

Keywords: NTX-010; Seneca valley virus; Small cell lung cancer; Virotherapy.

Copyright © 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1.
Figure 1.
CONSORT Diagram
Figure 2.
Figure 2.
Kaplan-Meier curves of (A) progression free survival and (B) overall survival by arm
Figure 3.
Figure 3.
Viral titer values for patients in NTX-010 arm (N=26).
Figure 4.
Figure 4.
Kaplan-Meier curves of PFS and OS for viral RNA detection at day 7 (A, B) and day 14 (C, D).

Source: PubMed

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