Efficacy analysis of MASTERKEY-265 phase 1b study of talimogene laherparepvec (T-VEC) and pembrolizumab (pembro) for unresectable stage IIIB-IV melanoma.

Targeted agents and immunotherapies: optimizing outcomes in melanoma

“…Dosing strategies of available agents, such as anti-CTLA-4 and anti-PD-1 antibodies, are being further evaluated to optimize clinical benefit and minimize toxicity 169 . Moreover, preliminary evidence of benefit and minimal toxicity has been obtained for several novel immunotherapeutics, such as indolamine 2,3-dioxygenase inhibitors and oncolytic viruses, when combined with an anti-PD-1 antibody 102,170 . Finally, surgical resection and radiotherapy remain relevant, and should be incorporated into patient care in the context of a multidisciplinary approach tailored to each patient.…”

“…Given the emerging evidence suggesting that the efficacy of anti-PD-1 antibodies is largely confined to patients with tumours that have robust baseline CD8 + T-cell infiltrates 99,100 , T-VEC could potentially be deployed before or concomitantly with immunecheckpoint inhibitors in those with few or no infiltrating T cells at baseline. Of note, preliminary reports have described high response rates in patients with advancedstage melanoma treated using the combination of T-VEC and ipilimumab (~50%) 101 , or pembrolizumab (~46%) 102 ; a phase III trial of pembrolizumab with and without T-VEC is underway (NCT02263508).…”

The benefits of immunotherapy combinations

“…A genetically engineered form of herpesvirus, T-VEC replicates in infected cells until they break apart and release tumour antigens into the blood that attract T cells. Researchers on the trial, which is being sponsored by Amgen of Thousand Oaks, California, reported in September that the combination of pembrolizumab and T-VEC shrank melanoma tumours to a greater degree than did either treatment alone 6 .…”

Development of Checkpoint Inhibitors for Sarcomas

“…[82][83][84] Talimogene laherparepvec (T-VEC), an oncolytic herpesvirus delivered intralesionally, has been approved for clinical use in patients with melanoma, and the combination of T-VEC with ICI resulted in exciting results in early phase clinical trials. 85, 86 The role of combinations of immunotherapies with demethylating agents such as decitabine, capable of enhancing the expression of tumor antigens, is also being investigated. 87,88 Nevertheless, once again the biologic diversity of sarcomas will likely pose a major challenge for the development of the potential of immunotherapy in this setting.…”