Abstract CT003: Initial results from an open-label phase 1b/2 study of RP1 oncolytic immunotherapy in solid organ transplant recipients with advanced cutaneous malignancies (ARTACUS)
Authors: Migden Michael R. , Chai-Ho Wanxing , Daniels Gregory A. , Medina Theresa , Wise-Draper Trisha M. , Kheterpal Meenal , Tang Jennifer C. , Ibrahim Sherrif F. , Bolotin Diana , Verschraegen Claire , Zeitouni Nathalie C. , Tsai Katy K. , Donthireddy Laxminarasimha , Bommareddy Praveen K. , Hou Jeannie W. , Hong Walter , Davar Diwakar 
Published: April 2024

Abstract
Background: Skin cancers are common post-transplant malignancies in solid organ transplant (SOT) recipients. The use of immune checkpoint inhibitors has improved outcomes in the general patient (pt) population but is associated with a high risk of allograft rejection in transplant recipients. RP1 is an oncolytic immunotherapy that expresses a fusogenic glycoprotein (GALV-GP-R−) and granulocyte-macrophage colony-stimulating factor (GM-CSF). The purpose of this study is to assess the safety and efficacy of single-agent RP1 in SOT recipients with skin cancer (NCT04349436).
Methods: The trial will enroll up to 65 transplant recipients with histologically confirmed advanced cutaneous squamous cell carcinoma (CSCC) and up to 10 pts with advanced non-CSCC skin cancer in 2 parts. Part A (completed) enrolled kidney and liver transplant recipients until safety was established, and Part B is enrolling kidney, liver, heart, and lung transplant recipients. Pts must have stable allograft function and ECOG performance status ≤1. Pts with visceral metastases are excluded. Pts receive an initial RP1 dose at 1 × 106 plaque-forming units (PFU)/mL followed by 1 × 107 PFU/mL after 2 weeks and continuing every 2 weeks until prespecified study endpoints are met. Tumor biopsies are collected for biomarker analyses and HSV-1 serostatus is monitored.
Results: At the data cutoff (Sept 18, 2023), 27 transplant recipients were enrolled (kidney, n = 22; liver, n = 4; lung, n = 1) with a median (range) age of 68 (48-86) years; 24 pts had CSCC and 3 had Merkel cell carcinoma. Nearly half of pts (44%) had metastatic disease at study baseline. The investigator-assessed objective response rate (ORR) for efficacy-evaluable pts was 35% (8/23); 22% of pts (5/23) had complete response (CR). Most responses were ongoing. The most common (&gt;20%) treatment-emergent adverse events were fatigue (33%), chills (26%), and pyrexia (26%). There was no evidence of allograft rejection. Eight deaths were reported; none were related to RP1. Immunohistochemistry from tumor biopsies indicated influx of CD8+ T cells and upregulation of PD-L1 expression after RP1 treatment. Additional biomarker data from gene expression analysis will be presented.
Conclusions: This is the first trial assessing single-agent RP1 activity in solid organ transplant recipients with advanced cutaneous malignancies. RP1 monotherapy showed compelling antitumor activity (ORR 35%; 22% CR) in evaluable pts. Additionally, RP1 monotherapy was well tolerated, and the safety profile was similar to non-immunocompromised pts with advanced skin cancers (IGNYTE study).
Citation Format: Michael R. Migden, Wanxing Chai-Ho, Gregory A. Daniels, Theresa Medina, Trisha M. Wise-Draper, Meenal Kheterpal, Jennifer C. Tang, Sherrif F. Ibrahim, Diana Bolotin, Claire Verschraegen, Nathalie C. Zeitouni, Katy K. Tsai, Laxminarasimha Donthireddy, Praveen K. Bommareddy, Jeannie W. Hou, Walter Hong, Diwakar Davar. Initial results from an open-label phase 1b/2 study of RP1 oncolytic immunotherapy in solid organ transplant recipients with advanced cutaneous malignancies (ARTACUS) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT003.