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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)110-119
Number of pages10
JournalJournal of Thoracic Oncology
Volume15
Issue number1
DOIs
StatePublished - Jan 2020

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Platinum
Placebos
Confidence Intervals
Viruses
Drug Therapy
Disease-Free Survival
Medical Futility
Neoplasms
Therapeutics
Picornaviridae
Tropism
Neutralizing Antibodies

Keywords

  • NTX-010
  • Seneca valley virus
  • Small cell lung cancer
  • Virotherapy

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

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. / 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.

In: Journal of Thoracic Oncology, Vol. 15, No. 1, 01.2020, p. 110-119.

Research output: Contribution to journalArticle

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. / 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. In: Journal of Thoracic Oncology. 2020 ; Vol. 15, No. 1. pp. 110-119.
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title = "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",
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.",
keywords = "NTX-010, Seneca valley virus, Small cell lung cancer, Virotherapy",
author = "Schenk, {Erin L.} and Mandrekar, {Sumithra J.} and Dy, {Grace K.} and Aubry, {Marie Christine} and Tan, {Angelina D.} and Dakhil, {Shaker R.} and Sachs, {Bradley A.} and Nieva, {Jorge J.} and Erin Bertino and {Lee Hann}, Christine and Schild, {Steven E.} and Wadsworth, {Troy W.} and Adjei, {Alex A.} and Molina, {Julian R.}",
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T1 - 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

T2 - North Central Cancer Treatment Group (Alliance) N0923 Study

AU - Schenk, Erin L.

AU - Mandrekar, Sumithra J.

AU - Dy, Grace K.

AU - Aubry, Marie Christine

AU - Tan, Angelina D.

AU - Dakhil, Shaker R.

AU - Sachs, Bradley A.

AU - Nieva, Jorge J.

AU - Bertino, Erin

AU - Lee Hann, Christine

AU - Schild, Steven E.

AU - Wadsworth, Troy W.

AU - Adjei, Alex A.

AU - Molina, Julian R.

PY - 2020/1

Y1 - 2020/1

N2 - 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.

AB - 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.

KW - NTX-010

KW - Seneca valley virus

KW - Small cell lung cancer

KW - Virotherapy

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