Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second-generation oncolytic herpesvirus in patients with unresectable metastatic melanoma

Neil N. Senzer, Howard L. Kaufman, Thomas Amatruda, Mike Nemunaitis, Tony Reid, Gregory Daniels, Rene Gonzalez, John Glaspy, Eric Whitman, Kevin Harrington, Howard Goldsweig, Tracey Marshall, Colin Love, Robert Coffin, John J. Nemunaitis

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Abstract

Purpose: Treatment options for metastatic melanoma are limited. We conducted this phase II trial to assess the efficacy of JS1/34.5-/47-/ granulocyte-macrophage colony-stimulating factor (GM-CSF) in stages IIIc and IV disease. Patients and Methods: Treatment involved intratumoral injection of up to 4 mL of 106 pfu/mL of JS1/34.5-/47-/GM-CSF followed 3 weeks later by up to 4 mL of 108 pfu/mL every 2 weeks for up to 24 treatments. Clinical activity (by RECIST [Response Evaluation Criteria in Solid Tumors]), survival, and safety parameters were monitored. Results: Fifty patients (stages IIIc, n = 10; IVM1a, n = 16; IVM1b, n = 4; IVM1c, n = 20) received a median of six injection sets; 74% of patients had received one or more nonsurgical prior therapies for active disease, including dacarbazine/temozolomide or interleukin-2 (IL-2). Adverse effects were limited primarily to transient flu-like symptoms. The overall response rate by RECIST was 26% (complete response [CR], n = 8; partial response [PR], n = 5), and regression of both injected and distant (including visceral) lesions occurred. Ninety-two percent of the responses had been maintained for 7 to 31 months. Ten additional patients had stable disease (SD) for greater than 3 months, and two additional patients had surgical CR. On an extension protocol, two patients subsequently achieved CR by 24 months (one previously PR, one previously SD), and one achieved surgical CR (previously PR). Overall survival was 58% at 1 year and 52% at 24 months. Conclusion: The 26% response rate, with durability in both injected and uninjected lesions including visceral sites, together with the survival rates, are evidence of systemic effectiveness. This effectiveness, combined with a limited toxicity profile, warrants additional evaluation of JS1/34.5-/47-/GM-CSF in metastatic melanoma. A US Food and Drug Administration-approved phase III investigation is underway.

Original languageEnglish (US)
Pages (from-to)5763-5771
Number of pages9
JournalJournal of Clinical Oncology
Volume27
Issue number34
DOIs
StatePublished - Dec 1 2009

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Phase II Clinical Trials
Herpesviridae
Granulocyte-Macrophage Colony-Stimulating Factor
Melanoma
temozolomide
Dacarbazine
Injections
Survival
United States Food and Drug Administration
Therapeutics
Interleukin-2
Survival Rate
Safety

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Senzer, Neil N. ; Kaufman, Howard L. ; Amatruda, Thomas ; Nemunaitis, Mike ; Reid, Tony ; Daniels, Gregory ; Gonzalez, Rene ; Glaspy, John ; Whitman, Eric ; Harrington, Kevin ; Goldsweig, Howard ; Marshall, Tracey ; Love, Colin ; Coffin, Robert ; Nemunaitis, John J. / Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second-generation oncolytic herpesvirus in patients with unresectable metastatic melanoma. In: Journal of Clinical Oncology. 2009 ; Vol. 27, No. 34. pp. 5763-5771.
@article{52162793c6c74d77a102e27e381819bb,
title = "Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second-generation oncolytic herpesvirus in patients with unresectable metastatic melanoma",
abstract = "Purpose: Treatment options for metastatic melanoma are limited. We conducted this phase II trial to assess the efficacy of JS1/34.5-/47-/ granulocyte-macrophage colony-stimulating factor (GM-CSF) in stages IIIc and IV disease. Patients and Methods: Treatment involved intratumoral injection of up to 4 mL of 106 pfu/mL of JS1/34.5-/47-/GM-CSF followed 3 weeks later by up to 4 mL of 108 pfu/mL every 2 weeks for up to 24 treatments. Clinical activity (by RECIST [Response Evaluation Criteria in Solid Tumors]), survival, and safety parameters were monitored. Results: Fifty patients (stages IIIc, n = 10; IVM1a, n = 16; IVM1b, n = 4; IVM1c, n = 20) received a median of six injection sets; 74{\%} of patients had received one or more nonsurgical prior therapies for active disease, including dacarbazine/temozolomide or interleukin-2 (IL-2). Adverse effects were limited primarily to transient flu-like symptoms. The overall response rate by RECIST was 26{\%} (complete response [CR], n = 8; partial response [PR], n = 5), and regression of both injected and distant (including visceral) lesions occurred. Ninety-two percent of the responses had been maintained for 7 to 31 months. Ten additional patients had stable disease (SD) for greater than 3 months, and two additional patients had surgical CR. On an extension protocol, two patients subsequently achieved CR by 24 months (one previously PR, one previously SD), and one achieved surgical CR (previously PR). Overall survival was 58{\%} at 1 year and 52{\%} at 24 months. Conclusion: The 26{\%} response rate, with durability in both injected and uninjected lesions including visceral sites, together with the survival rates, are evidence of systemic effectiveness. This effectiveness, combined with a limited toxicity profile, warrants additional evaluation of JS1/34.5-/47-/GM-CSF in metastatic melanoma. A US Food and Drug Administration-approved phase III investigation is underway.",
author = "Senzer, {Neil N.} and Kaufman, {Howard L.} and Thomas Amatruda and Mike Nemunaitis and Tony Reid and Gregory Daniels and Rene Gonzalez and John Glaspy and Eric Whitman and Kevin Harrington and Howard Goldsweig and Tracey Marshall and Colin Love and Robert Coffin and Nemunaitis, {John J.}",
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Senzer, NN, Kaufman, HL, Amatruda, T, Nemunaitis, M, Reid, T, Daniels, G, Gonzalez, R, Glaspy, J, Whitman, E, Harrington, K, Goldsweig, H, Marshall, T, Love, C, Coffin, R & Nemunaitis, JJ 2009, 'Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second-generation oncolytic herpesvirus in patients with unresectable metastatic melanoma', Journal of Clinical Oncology, vol. 27, no. 34, pp. 5763-5771. https://doi.org/10.1200/JCO.2009.24.3675

Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second-generation oncolytic herpesvirus in patients with unresectable metastatic melanoma. / Senzer, Neil N.; Kaufman, Howard L.; Amatruda, Thomas; Nemunaitis, Mike; Reid, Tony; Daniels, Gregory; Gonzalez, Rene; Glaspy, John; Whitman, Eric; Harrington, Kevin; Goldsweig, Howard; Marshall, Tracey; Love, Colin; Coffin, Robert; Nemunaitis, John J.

In: Journal of Clinical Oncology, Vol. 27, No. 34, 01.12.2009, p. 5763-5771.

Research output: Contribution to journalArticle

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T1 - Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second-generation oncolytic herpesvirus in patients with unresectable metastatic melanoma

AU - Senzer, Neil N.

AU - Kaufman, Howard L.

AU - Amatruda, Thomas

AU - Nemunaitis, Mike

AU - Reid, Tony

AU - Daniels, Gregory

AU - Gonzalez, Rene

AU - Glaspy, John

AU - Whitman, Eric

AU - Harrington, Kevin

AU - Goldsweig, Howard

AU - Marshall, Tracey

AU - Love, Colin

AU - Coffin, Robert

AU - Nemunaitis, John J.

PY - 2009/12/1

Y1 - 2009/12/1

N2 - Purpose: Treatment options for metastatic melanoma are limited. We conducted this phase II trial to assess the efficacy of JS1/34.5-/47-/ granulocyte-macrophage colony-stimulating factor (GM-CSF) in stages IIIc and IV disease. Patients and Methods: Treatment involved intratumoral injection of up to 4 mL of 106 pfu/mL of JS1/34.5-/47-/GM-CSF followed 3 weeks later by up to 4 mL of 108 pfu/mL every 2 weeks for up to 24 treatments. Clinical activity (by RECIST [Response Evaluation Criteria in Solid Tumors]), survival, and safety parameters were monitored. Results: Fifty patients (stages IIIc, n = 10; IVM1a, n = 16; IVM1b, n = 4; IVM1c, n = 20) received a median of six injection sets; 74% of patients had received one or more nonsurgical prior therapies for active disease, including dacarbazine/temozolomide or interleukin-2 (IL-2). Adverse effects were limited primarily to transient flu-like symptoms. The overall response rate by RECIST was 26% (complete response [CR], n = 8; partial response [PR], n = 5), and regression of both injected and distant (including visceral) lesions occurred. Ninety-two percent of the responses had been maintained for 7 to 31 months. Ten additional patients had stable disease (SD) for greater than 3 months, and two additional patients had surgical CR. On an extension protocol, two patients subsequently achieved CR by 24 months (one previously PR, one previously SD), and one achieved surgical CR (previously PR). Overall survival was 58% at 1 year and 52% at 24 months. Conclusion: The 26% response rate, with durability in both injected and uninjected lesions including visceral sites, together with the survival rates, are evidence of systemic effectiveness. This effectiveness, combined with a limited toxicity profile, warrants additional evaluation of JS1/34.5-/47-/GM-CSF in metastatic melanoma. A US Food and Drug Administration-approved phase III investigation is underway.

AB - Purpose: Treatment options for metastatic melanoma are limited. We conducted this phase II trial to assess the efficacy of JS1/34.5-/47-/ granulocyte-macrophage colony-stimulating factor (GM-CSF) in stages IIIc and IV disease. Patients and Methods: Treatment involved intratumoral injection of up to 4 mL of 106 pfu/mL of JS1/34.5-/47-/GM-CSF followed 3 weeks later by up to 4 mL of 108 pfu/mL every 2 weeks for up to 24 treatments. Clinical activity (by RECIST [Response Evaluation Criteria in Solid Tumors]), survival, and safety parameters were monitored. Results: Fifty patients (stages IIIc, n = 10; IVM1a, n = 16; IVM1b, n = 4; IVM1c, n = 20) received a median of six injection sets; 74% of patients had received one or more nonsurgical prior therapies for active disease, including dacarbazine/temozolomide or interleukin-2 (IL-2). Adverse effects were limited primarily to transient flu-like symptoms. The overall response rate by RECIST was 26% (complete response [CR], n = 8; partial response [PR], n = 5), and regression of both injected and distant (including visceral) lesions occurred. Ninety-two percent of the responses had been maintained for 7 to 31 months. Ten additional patients had stable disease (SD) for greater than 3 months, and two additional patients had surgical CR. On an extension protocol, two patients subsequently achieved CR by 24 months (one previously PR, one previously SD), and one achieved surgical CR (previously PR). Overall survival was 58% at 1 year and 52% at 24 months. Conclusion: The 26% response rate, with durability in both injected and uninjected lesions including visceral sites, together with the survival rates, are evidence of systemic effectiveness. This effectiveness, combined with a limited toxicity profile, warrants additional evaluation of JS1/34.5-/47-/GM-CSF in metastatic melanoma. A US Food and Drug Administration-approved phase III investigation is underway.

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