Phase IIIb safety results from an expanded-access protocol of talimogene laherparepvec for patients with unresected, stage IIIB-IVM1c melanoma

Jason Chesney, Sanjay Awasthi, Brendan Curti, Laura Hutchins, Gerald Linette, Pierre Triozzi, Marcus C.B. Tan, Russell E. Brown, John Nemunaitis, Eric Whitman, Christopher Windham, Jose Lutzky, Gerald F. Downey, Nicolas Batty, Thomas Amatruda

Research output: Contribution to journalArticle

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Abstract

Talimogene laherparepvec is a genetically modified herpes simplex virus-1-based oncolytic immunotherapy for the local treatment of unresectable cutaneous, subcutaneous, and nodal tumors in patients with melanoma recurrence following surgery. We aim to describe the safety of talimogene laherparepvec. Intralesional talimogene laherparepvec was administered at less than or equal to 4ml×106 PFU/ml at protocol day 1, then less than or equal to 4ml×108 PFU/ml 21 days later, and then every 14 days. Treatment continued until complete response, absence of injectable tumors, progressive disease, intolerance, or US Food and Drug Administration approval. Adverse events were graded during and 30 days after the end of treatment. Lesions suspected to have herpetic origin were tested for talimogene laherparepvec DNA by quantitative PCR (qPCR). Between September 2014 and October 2015, 41 patients were enrolled with stage IIIB (22%), IIIC (37%), IVM1a (34%), IVM1b (5%), and IVM1c (2%) melanoma. The median age was 72 (range: 32-96) years and 54% of the patients were men. Patients had an ECOG performance status of 0 (68%) or 1 (32%). The median treatment duration was 13.1 (3.0-41.1) weeks. Treatment-related adverse events of greater than or equal to grade 3 were reported in three (7.3%) patients and included vomiting, upper abdominal pain, chills, hyperhidrosis, nausea, pyrexia, and wound infection. Suspected herpetic lesions were swabbed in five (12%) patients. One of the five tested positive for talimogene laherparepvec DNA by qPCR, but this lesion had been injected previously with talimogene laherparepvec. During the study, five patients completed treatment because of complete response per investigators. In the clinical practice setting, talimogene laherparepvec has a safety profile comparable to that observed in previous clinical trials. Talimogene laherparepvec (IMLYGIC) is now approved in the US, European Union, and Australia.

Original languageEnglish (US)
Pages (from-to)44-51
Number of pages8
JournalMelanoma Research
Volume28
Issue number1
DOIs
StatePublished - Jan 1 2018

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Melanoma
Safety
Therapeutics
Hyperhidrosis
Drug Approval
Polymerase Chain Reaction
Chills
DNA
Human Herpesvirus 1
Wound Infection
European Union
Immunotherapy
Nausea
Abdominal Pain
Vomiting
Neoplasms
Fever
Research Personnel
Clinical Trials
Recurrence

All Science Journal Classification (ASJC) codes

  • Oncology
  • Dermatology
  • Cancer Research

Cite this

Chesney, Jason ; Awasthi, Sanjay ; Curti, Brendan ; Hutchins, Laura ; Linette, Gerald ; Triozzi, Pierre ; Tan, Marcus C.B. ; Brown, Russell E. ; Nemunaitis, John ; Whitman, Eric ; Windham, Christopher ; Lutzky, Jose ; Downey, Gerald F. ; Batty, Nicolas ; Amatruda, Thomas. / Phase IIIb safety results from an expanded-access protocol of talimogene laherparepvec for patients with unresected, stage IIIB-IVM1c melanoma. In: Melanoma Research. 2018 ; Vol. 28, No. 1. pp. 44-51.
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abstract = "Talimogene laherparepvec is a genetically modified herpes simplex virus-1-based oncolytic immunotherapy for the local treatment of unresectable cutaneous, subcutaneous, and nodal tumors in patients with melanoma recurrence following surgery. We aim to describe the safety of talimogene laherparepvec. Intralesional talimogene laherparepvec was administered at less than or equal to 4ml×106 PFU/ml at protocol day 1, then less than or equal to 4ml×108 PFU/ml 21 days later, and then every 14 days. Treatment continued until complete response, absence of injectable tumors, progressive disease, intolerance, or US Food and Drug Administration approval. Adverse events were graded during and 30 days after the end of treatment. Lesions suspected to have herpetic origin were tested for talimogene laherparepvec DNA by quantitative PCR (qPCR). Between September 2014 and October 2015, 41 patients were enrolled with stage IIIB (22{\%}), IIIC (37{\%}), IVM1a (34{\%}), IVM1b (5{\%}), and IVM1c (2{\%}) melanoma. The median age was 72 (range: 32-96) years and 54{\%} of the patients were men. Patients had an ECOG performance status of 0 (68{\%}) or 1 (32{\%}). The median treatment duration was 13.1 (3.0-41.1) weeks. Treatment-related adverse events of greater than or equal to grade 3 were reported in three (7.3{\%}) patients and included vomiting, upper abdominal pain, chills, hyperhidrosis, nausea, pyrexia, and wound infection. Suspected herpetic lesions were swabbed in five (12{\%}) patients. One of the five tested positive for talimogene laherparepvec DNA by qPCR, but this lesion had been injected previously with talimogene laherparepvec. During the study, five patients completed treatment because of complete response per investigators. In the clinical practice setting, talimogene laherparepvec has a safety profile comparable to that observed in previous clinical trials. Talimogene laherparepvec (IMLYGIC) is now approved in the US, European Union, and Australia.",
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Chesney, J, Awasthi, S, Curti, B, Hutchins, L, Linette, G, Triozzi, P, Tan, MCB, Brown, RE, Nemunaitis, J, Whitman, E, Windham, C, Lutzky, J, Downey, GF, Batty, N & Amatruda, T 2018, 'Phase IIIb safety results from an expanded-access protocol of talimogene laherparepvec for patients with unresected, stage IIIB-IVM1c melanoma', Melanoma Research, vol. 28, no. 1, pp. 44-51. https://doi.org/10.1097/CMR.0000000000000399

Phase IIIb safety results from an expanded-access protocol of talimogene laherparepvec for patients with unresected, stage IIIB-IVM1c melanoma. / Chesney, Jason; Awasthi, Sanjay; Curti, Brendan; Hutchins, Laura; Linette, Gerald; Triozzi, Pierre; Tan, Marcus C.B.; Brown, Russell E.; Nemunaitis, John; Whitman, Eric; Windham, Christopher; Lutzky, Jose; Downey, Gerald F.; Batty, Nicolas; Amatruda, Thomas.

In: Melanoma Research, Vol. 28, No. 1, 01.01.2018, p. 44-51.

Research output: Contribution to journalArticle

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AU - Brown, Russell E.

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N2 - Talimogene laherparepvec is a genetically modified herpes simplex virus-1-based oncolytic immunotherapy for the local treatment of unresectable cutaneous, subcutaneous, and nodal tumors in patients with melanoma recurrence following surgery. We aim to describe the safety of talimogene laherparepvec. Intralesional talimogene laherparepvec was administered at less than or equal to 4ml×106 PFU/ml at protocol day 1, then less than or equal to 4ml×108 PFU/ml 21 days later, and then every 14 days. Treatment continued until complete response, absence of injectable tumors, progressive disease, intolerance, or US Food and Drug Administration approval. Adverse events were graded during and 30 days after the end of treatment. Lesions suspected to have herpetic origin were tested for talimogene laherparepvec DNA by quantitative PCR (qPCR). Between September 2014 and October 2015, 41 patients were enrolled with stage IIIB (22%), IIIC (37%), IVM1a (34%), IVM1b (5%), and IVM1c (2%) melanoma. The median age was 72 (range: 32-96) years and 54% of the patients were men. Patients had an ECOG performance status of 0 (68%) or 1 (32%). The median treatment duration was 13.1 (3.0-41.1) weeks. Treatment-related adverse events of greater than or equal to grade 3 were reported in three (7.3%) patients and included vomiting, upper abdominal pain, chills, hyperhidrosis, nausea, pyrexia, and wound infection. Suspected herpetic lesions were swabbed in five (12%) patients. One of the five tested positive for talimogene laherparepvec DNA by qPCR, but this lesion had been injected previously with talimogene laherparepvec. During the study, five patients completed treatment because of complete response per investigators. In the clinical practice setting, talimogene laherparepvec has a safety profile comparable to that observed in previous clinical trials. Talimogene laherparepvec (IMLYGIC) is now approved in the US, European Union, and Australia.

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