An evaluation of talimogene laherparepvec for the treatment of melanoma

ABSTRACT

Introduction: Intralesional therapies have emerged as effective immune therapies for locally advanced and metastatic melanoma. Talimogene laherparepvec (T-VEC), an oncolytic virus derived from the herpes simplex 1 (HSV-1) virus, is the first and only FDA approved intralesional therapy for recurrent, unresectable cutaneous, subcutaneous or nodal metastases from melanoma.

Areas covered: We discuss results from clinical trials of T-VEC including data on safety, biodistribution, and viral shedding, which established the current treatment protocol and basis for FDA approval. Data are presented from early implementation of T-VEC in clinical practice. We explore the use of T-VEC in the neoadjuvant setting and in combination with anti-CTLA-4 and PD-1 therapies, including available evidence to support a mechanism for the observed synergistic effect.

Expert opinion: Intralesional T-VEC is effective for unresectable stage III and IVa melanoma, with early clinical results comparing favorably to response rates from clinical trials. Clinical applications will likely increase as more data become available on its use in the neoadjuvant setting and in combination with other systemic immune therapies. We expect the fields of intralesional therapy and viral oncotherapy to expand as we better understand how to manipulate the tumor microenvironment and host immune response to cancer.

KEYWORDS:

• Melanoma
• metastatic melanoma
• in-transit melanoma
• intralesional therapy
• oncolytic virus
• immunotherapy
• Talimogene laherparepvec
• T-VEC

Article highlights

• Derived from herpes simplex virus type I (HSV-1), talimogene laherparepvec (T-VEC) is a first-in-class oncolytic virus engineered to preferentially replicate in and lyse tumor cells while stimulating a tumor-specific host immune response.

• Intralesional T-VEC is not pathogenic in normal tissues, produces minimal adverse effects, and does not transmit herpesvirus to patients’ close contacts.

• T-VEC is an effective intralesional therapy for advanced and metastatic melanoma, inducing durable response in a significant proportion of patients.

• T-VEC is believed to produce local and abscopal effects based on the demonstration of systemic antitumor immunity and response in both injected and un-injected lesions.

• Testing in the neoadjuvant setting demonstrates that clinical response assessments may underestimate pathologic response to T-VEC, as complete pathologic response was found in 21% of patients undergoing resection of lesions treated by T-VEC.

• Neoadjuvant treatment with T-VEC may help select patients who are most likely to benefit from surgery while improving margin-negative resection rates.

• Early studies suggest that combination therapy with intralesional T-VEC and systemically delivered anti-CTLA4 and anti-PD-1 produces higher response rates than either therapy in isolation, and final results of a phase III trial are awaited.

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Declaration of interest

J Zager has received research funding from Novartis, Philogen, Delcath Systems, Amgen, Provectus, served on Advisory Boards for Merck, Sanofi-Regeneron, Agmgen and Array Biopharma and participates in Speakers Bureau's for Array Biopharma and Sun Pharma. J Zager is also a consultant for Philogen and Amgen and on the Medical Advisory Board for Delcath. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.