550 ARTACUS: An open-label, multicenter, phase 1b/2 study of RP1 in solid organ transplant recipients with advanced cutaneous malignancies

Background Solid organ transplantation (SOT) has emerged as an important lifesaving procedure for patients with a wide range of end-organ diseases characterized by dysfunction or specific function failure. SOT rejection is major complication requiring (pts) to undergo lifelong immunosuppression prevent allograft rejection. 1 Skin cancers (SCs) including cutaneous squamous cell carcinoma (CSCC) are common post transplant malignancies. 2 SC in pts generally managed surgical resection, radiation therapy and chemotherapy targeted therapy. Use immune checkpoint inhibitors recipients improved outcomes but associated the high risk 3–5 Thus, there unmet need safe effective treatment that also protects from RP1 oncolytic virus (HSV-1) expresses fusogenic glycoprotein (GALV-GP R-) granulocyte macrophage colony stimulating factor (GM-CSF). In preclinical studies, induced immunogenic tumor death provided potent systemic anti-tumor activity 6 clinical data combination nivolumab demonstrated rate deep durable response advanced SCs. 7 The objective this study assess safety efficacy single agent kidney liver SCs, focus on CSCC. After determining tolerability initial cohort transplants may enroll heart lung recipients. Methods This will up 65 evaluable locally metastatic Key inclusion criteria confirmed recurrent, CSCC 10 non-CSCC SC, stable ECOG performance status ≤1. Pts prior anti-cancer allowed. exclusion therapy, active herpetic infections complications HSV-1 infection history graft within 12 months. receive dose x 10^6 plaque-forming units (PFU) RP1. Two weeks later they 10^7 PFU continue every two until pre-specified endpoints met. be administered intra-tumoral injection through imaging guidance clinically appropriate. primary trial determined ORR Additional secondary include DOR, CR, DCR, PFS OS. Trial Registration NCT04349436 References Frohn C, Fricke L, Puchta JC, Kirchner H. effect HLA-C matching acute renal Nephrol Dial Transplant 2001; 16 (2):355–60. Madeleine MM, Patel NS, Plasmeijer EI, Engels EA, Bouwes Bavinck JN, Toland AE, Green AC; Keratinocyte Carcinoma Consortium (KeraCon) Immunosuppression Working Group. Epidemiology keratinocyte carcinomas after transplantation. Br J Dermatol 2017; 177 (5):1208–1216. Spain Higgins R, Gopalakrishnan K, Turajlic S, Gore M, Larkin J. Acute inhibitor melanoma. Ann Oncol 2016; 27 (6):1135–1137. Herz Höfer T, Papapanagiotou Leyh Meyenburg Schadendorf D, Ugurel Roesch A, Livingstone E, Schilling B, Franklin C. Checkpoint chronic failure recipient. Eur Cancer 67 :66-72. Kittai AS, Oldham H, Cetnar J, Taylor M. Immune ptss. Immunother 2017;40(7):277–281. Thomas Kuncheria Roulstone V, Kyula Mansfield Bommareddy PK, Smith Kaufman HL, Harrington KJ, Coffin RS. Development new fusion-enhanced immunotherapy platform based herpes simplex type 1. 2019 ;7(1):214. Middleton Aroldi F, Sacco Milhem Curti Vanderwalde Baum Samson Pavlick Chesney Niu Rhodes Bowles Conry Olsson-Brown Earl-Laux P, Deterding Samakoglu K. 422 An open-label, multicenter, phase 1/2 RP1, enhanced potency HSV, combined nivolumab: updated results skin cancer cohorts. 2020; 8 (3): doi: 10.1136/jitc-2020-SITC2020.0422 Ethics Approval was approved institutional review board local ethics committee at each participating site. Informed consent obtained before trial.