An open-label, multicenter, phase 1b/2 study of RP1, a first-in-class, enhanced potency oncolytic virus in solid organ transplant recipients with advanced cutaneous malignancies (ARTACUS)

TPS9597 Background: RP1 is an oncolytic virus (HSV-1) that expresses a fusogenic glycoprotein (GALV-GP R-) and granulocyte macrophage colony stimulating factor (GM-CSF). In preclinical studies, RP1 induced immunogenic tumor cell death and provided potent systemic anti-tumor activity. Clinical data in combination with nivolumab has demonstrated a high rate of deep and durable response in patients with advanced skin cancer. Solid organ transplantation (SOT) is an important lifesaving procedure for patients with a wide range of end-organ diseases, but requires patients (pts) to undergo lifelong immunosuppression to prevent allograft rejection, and skin cancers (SCs) – including cutaneous squamous cell carcinoma (CSCC) – are common post-transplant malignancies. SC in SOT pts is generally managed with surgical resection, radiation therapy, and chemotherapy or targeted therapy. The use of immune checkpoint inhibitors in SOT recipients has improved outcomes but is associated with a high risk of allograft rejection. Thus, there is a high unmet need for a safe and effective treatment that also protects pts from allograft rejection. The objective of this study is to assess the safety and efficacy of single-agent RP1 in SOT patients with SCs, with a focus on CSCC. Methods: This study will enroll up to 65 evaluable SOT pts with locally advanced or metastatic SCs. The study has two parts. In Part A, pts will receive an initial dose of 1 x 106 plaque-forming units (PFU) of RP1. Two weeks later they will receive 1 x 107 PFU of RP1 and continue every two weeks until pre-specified study endpoints are met. In Part B, after determining the safety and tolerability in the initial cohort with kidney and liver transplants, the study may also enroll heart and lung transplant recipients. RP1 will be administered by intra-tumoral injection, utilizing image guidance as clinically appropriate. Key inclusion criteria are pts with confirmed recurrent, locally advanced or metastatic CSCC and up to 10 pts with non-CSCC SC, stable allograft function and ECOG performance status of ≤1. Pts with prior systemic anti-cancer treatment are allowed. Key exclusion criteria are prior treatment with an oncolytic therapy, active herpetic infections or prior complications of HSV-1 infection and a history of organ graft rejection within 12 months. The primary objective of the trial is to assess efficacy determined by objective response rate and safety of single agent RP1. Additional secondary endpoints include duration of response, complete response rate, disease control rate, progression-free survival and overall survival. Clinical trial information: NCT04349436.