Presenting Author: Christina Davis, PharmD, University of Colorado Hospital, Aurora, CO
Co-Authors: Caroline Robert, MD, PhD, Gustave Roussy and Paris-Saclay University, Villejuif, France; Michael K. Wong, MD, PhD, Roswell Park Comprehensive Cancer Center, Buffalo, NY; Mark R. Middleton, MD, PhD, FRCP, Churchill Hospital and University of Oxford, UK; Mohammed M. Milhem, MBBS, Holden Comprehensive Cancer Center, University of Iowa, Iowa City; Joseph J. Sacco, PhD, FRCP, The Clatterbridge Cancer Centre, Wirral, and University of Liverpool, UK; Judith Michels, MD, PhD, Département de Médecine Oncologique, Gustave Roussy; Gino K. In, MD, University of Southern California Norris Comprehensive Cancer Center, Los Angeles; Eva Muñoz Couselo, MD, PhD, Vall d’Hebron Institute of Oncology and Vall d’Hebron Hospital Medical Oncology Department, Barcelona, Spain; Dirk Schadendorf, MD, West German Cancer Center, University Hospital Essen, Germany; Georgia M. Beasley, MD, MHSc, Duke Cancer Institute, Duke University, Durham, NC; Jiaxin Niu, MD, PhD, Banner MD Anderson Cancer Center, Gilbert, AZ; Bartosz Chmielowski, MD, PhD, Jonsson Comprehensive Cancer Center, University of California Los Angeles; Trisha M. Wise-Draper, MD, PhD, University of Cincinnati Cancer Center, University of Cincinnati, OH; Tawnya Lynn Bowles, MD, Intermountain Medical Center, Murray, UT; Katy K. Tsai, MD, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, CA; Céleste Lebbé, MD, PhD, Université Paris Cité, AP-HP Dermato-Oncology and CIC, Cancer Institute APHP. Nord–Université Paris Cité, INSERM U976, Saint Louis Hospital, Paris, France; Caroline Gaudy-Marqueste, MD, PhD, Aix-Marseille Université, APHM, Centre de Recherche en Cancérologie de Marseille, INSERM U1068, CNRS, UMR7258, UM105, Hôpital Timone, CEPCM, Dermatology and Skin Cancer Department, Marseille, France; Adel Samson, PhD, Leeds Institute of Medical Research at St. James’s, University of Leeds, UK; Jason A. Chesney, MD, PhD, James Graham Brown Cancer Center, University of Louisville, KY; Anna C. Pavlick, MD, MBA, Weill Cornell Medical College, New York, NY; Ari M. VanderWalde, MD, MPH, FACP, West Cancer Center and Research Institute, Germantown, TN; Kevin Harrington, PhD, The Institute of Cancer Research/Royal Marsden NIHR Biomedical Research Centre, London, UK; Marcus Viana, MD, Laxminarasimha Donthireddy, PhD, Alina Monteagudo, PhD, Junhong Zhu, PhD, Jeannie W. Hou, MD, Aaron Clack, PhD, and Praveen K. Bommareddy, PhD, MS, Replimune, Inc., Woburn, MA
BACKGROUND: RP1 is a herpes simplex virus type 1–based oncolytic immunotherapy currently in clinical development that is administered via intratumoral injection. RP1 plus nivolumab has demonstrated deep and durable responses with a favorable safety profile in advanced melanoma.
OBJECTIVE: To assess the biodistribution and shedding profiles from the skin cancer cohorts of the ongoing IGNYTE clinical trial (NCT03767348), thus informing the administration and handling methodology for RP1.
METHODS: In this open-label, multicenter phase 1/2 study, patients with advanced cancers were treated with the combination RP1 plus nivolumab. After RP1 injections into superficial and deep lesions, injection sites were covered with occlusive dressings. Samples from blood, urine, dressing exteriors, injection sites, oral mucosa, and lesions of suspected herpetic origin were assessed during predose, treatment, and follow-up visits for RP1 DNA by quantitative polymerase chain reaction assay. Positive RP1 DNA swab samples were further assessed by 50% tissue culture infectious dose (TCID50) assay for the presence of live virus.
RESULTS: This analysis included 1573 blood, 1976 urine, 2052 oral mucosa, 1114 dressings, and 1947 injection-site swab samples collected from 278 patients with skin cancer. RP1 DNA was detected in 7.8% of blood, 0.2% of urine, and 18.4% of injection-site swab samples. The incidence of RP1 detection on injection-site dressing exteriors (9.5% of 1114 samples) was lower than that from the injection sites (18.4% of 1947 samples), demonstrating that dressings act as a barrier to RP1 dissemination. RP1 DNA was very rarely present on oral mucosa (0.9% of 2052 samples). At follow-up, RP1 DNA was detected only in injection-site swab samples. All available samples were confirmed to be negative for live virus by TCID50 assay. A total of 8 swab samples from 7 patients from different locations were collected from areas of suspected herpetic infection; none tested positive for infectious virus. No communal or secondary transmission was reported.
CONCLUSION: RP1 DNA was primarily detected on the immediate surface of injected lesions. Overlying occlusive dressings appear to serve as a protective barrier against RP1 DNA dissemination. No infectious live virus was detected in samples from follow-up visits. These findings indicate that the risk of infection and transmission of RP1 is negligible. Oncolytic immunotherapy such as RP1 is emerging as an integral part of cancer therapeutics. Defining the biodistribution and shedding potential of these agents will be important for pharmacy staff and caregivers to develop the educational activities and best practices necessary to properly handle these agents.