Presenting Author: Christina Davis, PharmD, BCOP, University of Colorado Hospital, Aurora, CO
Co-Authors: Praveen K. Bommareddy, PhD, BPharm, MS, and Alina Monteagudo, PhD, Replimune, Woburn, MA; Mohammed M. Milhem, MD, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA; Joseph J. Sacco, MD, The Clatterbridge Centre and University of Liverpool, Liverpool, England; Tawnya Lynn Bowles, MD, Intermountain Medical Center, Murray, UT; Katy K. Tsai, MD, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA; Gino K. In, MD, MPH, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA; Eva Muñoz-Couselo, MD, PhD, Vall d’Hebron Institute of Oncology and Vall d’Hebron Hospital Medical Oncology Department, Barcelona, Spain; Ari M. VanderWalde, MD, FACP, MA, MPH, West Cancer Center and Research Institute, Germantown, TN; Jason Alan Chesney, MD, PhD, James Graham Brown Cancer Center, University of Louisville, Louisville, KY; Judith Michels, MD, PhD, Gustave Roussy, Département de Médecine Oncologique, Villejuif, France; Adel Samson, PhD, MBChB, MRCP, BSc, Leeds Institute of Medical Research at St. James’s, University of Leeds, Leeds, England; Georgia M. Beasley, MD, Duke Cancer Institute, Duke University, Durham, NC; Trisha M. Wise-Draper, MD, PhD, University of Cincinnati, Cincinnati, OH; Dirk Schadendorf, MD, West German Cancer Center, University Hospital Essen, Essen, Germany; Fade Mahmoud, MD, The T.W. Lewis Melanoma Center of Excellence, Banner MD Anderson Cancer Center at Banner Gateway Medical Center, Gilbert, AZ; Michael K. Wong, MD, PhD, The University of Texas MD Anderson Cancer Center, Houston, TX; Marcus Viana, MD, Jeannie W. Hou, MD, Aaron Clack, PhD, and Robert S. Coffin, PhD, Replimune, Woburn, MA; Mark R. Middleton, PhD, FRCP, Churchill Hospital and the University of Oxford, Oxford, England; Bartosz Chmielowski, MD, PhD, Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA
BACKGROUND: RP1 is an HSV-1–based tumor-directed oncolytic immunotherapy modified to enhance safety and increase oncolytic potential that is administered via intratumoral injection. To date, RP1 plus nivolumab has demonstrated clinical activity with an acceptable safety profile in a variety of cancers.
OBJECTIVE: To assess biodistribution and shedding data from 87 patients enrolled in the phase 1 dose expansion (n=14) and phase 2 (n=73) cohorts from the ongoing IGNYTE clinical trial (NCT03767348).
METHODS: In an open-label, multicenter phase 1/2 study, patients with advanced cancers received the combination of RP1 and nivolumab. RP1 was injected into both superficial and deep lesions; the 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 for RP1 DNA by quantitative polymerase chain reaction assay. Positive RP1 DNA samples were further assessed for infectious virus by 50% tissue culture infectious dose (TCID50) assay.
RESULTS: This analysis included 791 blood, 894 urine, 931 oral mucosa, 525 dressings, and 914 injection-site swab samples collected from 87 patients. RP1 DNA was detected in 16.9% of blood, 0.9% of urine, and 28.1% of injection-site swab samples, suggesting the local presence of RP1. The incidence of RP1 on injection-site dressings (8.2% of 525 samples) was lower than that from the injection site (28.1% of 914 samples), suggesting that dressings act as an effective barrier. RP1 DNA was present at low levels on oral mucosa (1.9% of 931 samples). At follow-up, RP1 DNA was only found on the injected lesion surface (5.4%/2.4% of patients at 30/60 days, respectively, after last dose). All but 1 swab that was positive for RP1 DNA (indicating the presence of a therapeutic agent at the sample site) tested negative for infectious virus by TCID50; all follow-up samples were negative. No RP1 DNA was found on swabs tested from potential herpetic lesions, with no reports of herpetic infection in caregivers.
CONCLUSION: RP1 DNA was primarily detected on the surface of injected lesions, with dressings appearing to serve as a protective barrier against RP1 DNA dissemination. These findings suggest that the risk of infection and transmission of RP1 is minimal. As the use of viral oncolytic immunotherapies is incorporated more into patient care, pharmacy staff and caregiver understanding of the biodistribution and shedding potential will be critical for the proper handling of and education surrounding these agents.
These data were previously submitted to and accepted for presentation at the Society for Immunotherapy of Cancer 2023 annual meeting.
- Thomas S, Kuncheria L, Roulstone V, et al. Development of a new fusion-enhanced oncolytic immunotherapy platform based on herpes simplex virus type 1. J Immunother Cancer. 2019;7:214.
- Middleton MR, Aroldi F, Sacco J, et al. An open-label, single-arm, phase II clinical trial of RP1, an enhanced potency oncolytic herpes virus, combined with nivolumab in four solid tumor types: initial results from the skin cancer cohorts. J Clin Oncol. 2020;38(suppl 15):e22050.