9581 Background: Cutaneous lymphomas (CL) and non-melanoma skin cancers (NMSC) present with skin lesions and can often be treated with local therapies. However, some do not respond or relapse, underlining the need for new treatment options. Intralesional oncolytic virotherapy with genetically modified Herpes simplex 1 virus called Talimogene laherparepvec (T-VEC) was approved for cutaneous melanoma. Given previous reports on oncolytic virotherapy in non-melanoma tumors, we investigated the effect of intralesional T-VEC in patients with CL and NMSC. Methods: Patients with CL and NMSC without extracutaneous spread were eligible (NCT03458117). They were treated according to the standard for up to 8 injections. We assessed clinical response of injected and, whenever possible, non-injected lesions using response criteria for intratumoral therapies (itRECIST). Safety was assessed using CTCAE v5 criteria. To evaluate T-VEC induced changes, we collected tumor biopsies at baseline, after 2 and 5 injections. We performed multiplex immunohistochemistry for CD3, CD8, CD79a, CD56, CD11c and FoxP3 and evaluated the changes using Akoya Bioscience technology. Results: Twenty-seven patients were enrolled into the study: 19pts with cutaneous B-cell lymphoma (CBCL), 5pts with cutaneous T-cell lymphoma, 1pt with cutaneous squamous cell carcinoma and 1pt with Merkel cell carcinoma. The mean age was 61.9yrs. In total, 26pts have received at least one intralesional T-VEC, one patient has withdrawn consent before the first infusion. Patients received median of 7 injections, 11pts (44%) have received 8 planned injections. Therapy was well tolerated with treatment related fever, flu-like symptoms and ulceration of the injected tumor being the most common treatment related adverse events (AE) (34% each). Three patients (12%) had grade 3 AE. Of the injected lesions, 84% demonstrated response, with reduction of the elevation in 84% and reduction of redness of the tumor in 68%. Non-injected response was 40% and overall response was 32%. Tissue samples of 18pts were available for analysis. Following T-VEC injections, responding lesions had an increase of CD8+ and decrease of FoxP3+ cells, while all lesions had an increase of CD56+ cells and slight reduction of CD79a+ cells. Responding CBCL samples had increased CD3+ cells, whereas all samples had an initial reduction of CD79a+ and CD11c+ cells, independent of response. Conclusions: Oncolytic virotherapy with intralesional T-VEC induces clinical responses and is tolerated without any unexpected toxicities in patients with locally advanced cutaneous lymphomas and NMSC. T-VEC induces activation of immune response, with differences in responding and non-responding lesions. T-VEC represents a viable treatment option for patients with CL and NMSC, and should be investigated in larger controlled clinical trials. Clinical trial information: NCT03458117 .
