PT - JOURNAL ARTICLE AU - Middleton, Mark AU - Aroldi, Francesca AU - Sacco, Joseph AU - Milhem, Mohammed AU - Curti, Brendan AU - MBioeth, Ari VanderWalde AU - Baum, Scott AU - Samson, Adel AU - Pavlick, Anna AU - Chesney, Jason AU - Niu, Jiaxin AU - Rhodes, Terence AU - Bowles, Tawnya AU - Conry, Robert AU - Olsson-Brown, Anna AU - Laux, Douglas Earl AU - Kaufman, Howard AU - Bommareddy, Praveen AU - Deterding, Alex AU - Samakoglu, Selda AU - Coffin, Robert AU - Harrington, Kevin TI - 422 An open-label, multicenter, phase 1/2 clinical trial of RP1, an enhanced potency oncolytic HSV, combined with nivolumab: updated results from the skin cancer cohorts AID - 10.1136/jitc-2020-SITC2020.0422 DP - 2020 Nov 01 TA - Journal for ImmunoTherapy of Cancer PG - A257--A257 VI - 8 IP - Suppl 3 4099 - http://jitc.bmj.com/content/8/Suppl_3/A257.1.short 4100 - http://jitc.bmj.com/content/8/Suppl_3/A257.1.full SO - J Immunother Cancer2020 Nov 01; 8 AB - Background RP1 is an enhanced potency oncolytic HSV encoding a fusogenic protein (GALV-GP R-) and GM-CSF which has previously demonstrated tolerable safety and tumor regression alone and with nivolumab in patients with a number of tumor types. Updated data from the phase 1 expansion with nivolumab, melanoma phase 2 (enrollment complete) and non-melanoma skin cancer (NMSC; enrollment ongoing) cohorts will be presented (NCT03767348). Enrollment of a further 125 patient anti-PD1 refractory cutaneous melanoma cohort; and activation of a cohort of anti-PD1 refractory NSCLC is underway.Methods Stage IIIb-IV melanoma patients for whom anti-PD-1 was indicated or who were refractory to prior anti-PD-1 alone or in combination with anti-CTLA-4, were enrolled. NMSC patients were anti-PD1 naïve. Patients received ≤8 doses of RP1 (≤10 mL/visit Q2W; first dose 106 PFU/mL then 107 PFU/mL) with nivolumab (240 mg IV Q2W for 4 months then 480 mg IV Q4W up to 2 years) from the second RP1 dose.Results As of 24th June 2020, 36 melanoma and 16 NMSC patients had been enrolled with follow up of <1–17 months. Of the melanoma patients, 16 previously anti-PD1 treated cutaneous (8 also prior anti-CTLA-4), 8 anti-PD1 naïve cutaneous, 6 mucosal, and 6 uveal. Of the NMSC patients, 10 had squamous cell (CSCC), 3 had a basal cell, 1 had Merkel cell carcinomas, and 2 had angiosarcoma. Treatment emergent adverse events (TEAEs) remain consistent with phase 1, with RP1 side effects generally of Grade 1/2 constitutional-type symptoms, with no exacerbation of the side effects expected for nivolumab. At the data cut-off, 5 previously anti-PD1 treated (4 also anti-CTLA-4) cutaneous melanoma patients, 4 anti-PD1 naïve cutaneous melanoma patients, two mucosal melanoma patients (one anti-PD1 refractory) and one uveal melanoma patient (ipi/nivo refractory) have achieved response (WHO criteria for uveal). For NMSC, for the 13 patients with >8 weeks follow up, one of two angiosarcoma patients and seven of eight CSCC patients (5 CR) have achieved response (CSCC ORR 87.5%; CR rate 62.5%, including of uninjected visceral disease). Tumor biopsies in patients continue to routinely show immune activation, including robust recruitment of CD8+ T cells, reversal of T cell exclusion, and increased PD-L1 expression. Treatment remains ongoing, and current data will be presented.Conclusions RP1 and nivolumab have continued to be well tolerated, with continued promising anti-tumor activity in patients with skin cancers, including those with anti-PD1 refractory and other difficult to treat melanomas, and in patients with CSCC.