Patterns of Clinical Response with Talimogene Laherparepvec (T-VEC) in Patients with Melanoma Treated in the OPTiM Phase III Clinical Trial

Abstract

PurposeTalimogene laherparepvec (T-VEC) is an oncolytic immunotherapy designed to induce tumor regression of injected lesions through direct lytic effects, and of uninjected lesions through induction of systemic antitumor immunity. In this study, we describe the patterns and time course of response to T-VEC from the phase III OPTiM trial of 436 patients with unresected stages IIIB–IV melanoma.MethodsLesion-level response analyses were performed based on the type of lesion (injected or uninjected cutaneous, subcutaneous, or nodal lesions; or visceral lesions [uninjected]), and the best percentage change from baseline of the sum of products of the longest diameters was calculated. Patients randomized to T-VEC (n = 295) who experienced a durable response (continuous partial or complete response for ≥6 months) were evaluated for progression prior to response (PPR), defined as the appearance of a new lesion or >25 % increase in total baseline tumor area.ResultsT-VEC resulted in a decrease in size by ≥50 % in 64 % of injected lesions (N = 2116), 34 % of uninjected non-visceral lesions (N = 981), and 15 % of visceral lesions (N = 177). Complete resolution of lesions occurred in 47 % of injected lesions, 22 % of uninjected non-visceral lesions, and 9 % of visceral lesions. Of 48 patients with durable responses, 23 (48 %) experienced PPR, including 14 who developed new lesions only. No difference in overall survival was observed, and median duration of response was not reached in patients with PPR versus those without PPR.ConclusionsResponses in uninjected lesions provide validation of T-VEC-induced systemic immunotherapeutic effects against melanoma. PPR did not negatively impact the clinical effectiveness of T-VEC.Electronic supplementary materialThe online version of this article (doi:10.1245/s10434-016-5286-0) contains supplementary material, which is available to authorized users.

Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy

“…In the pivotal single agent study of talimogene laherparepvec, a decrease in tumor size was observed in 15% of evaluable, noninjected, measurable visceral lesions (Andtbacka et al, 2015;Andtbacka et al, 2016). We also observed Figure 6) it is possible that the late timing of the biopsies (with week 6 occurring 2 weeks after the previous talimogene laherparepvec injection) was not optimal to address this question.…”

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“…Oncolytic herpes viruses (oHSVs) are members of an emerging class of cancer therapeutics that can selectively infect, replicate in, and lyse tumor cells without causing significant damage to the surrounding normal stroma 7 . Although these direct lytic effects are important in themselves, they can also promote an adaptive antitumor immune response that can help eradicate local tumors and distant metastases alike 8, 9. The most pertinent example of this immunologic activity is currently found in Imlygic (Talimogene Laherparepvec), an oHSV that encodes the gene for granulocyte-macrophage colony-stimulating factor and the first oncolytic virus to be approved by the US Food and Drug Administration (FDA) as a cancer therapeutic.…”