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705 Biodistribution and shedding analysis following RP1 oncolytic immunotherapy dosing in patients from the IGNYTE clinical trial
  1. Praveen K Bommareddy1,
  2. Alina Monteagudo1,
  3. Mohammed Milhem2,
  4. Joseph J Sacco3,4,
  5. Tawnya Lynn Bowles5,
  6. Katy K Tsai6,
  7. Gino K In7,
  8. Eva Muñoz-Couselo8,
  9. Ari M VanderWalde9,
  10. Jason Alan Chesney10,
  11. Judith Michels11,
  12. Adel Samson12,
  13. Georgia M Beasley13,
  14. Trisha M Wise-Draper14,
  15. Dirk Schadendorf15,
  16. Fade Mahmoud16,
  17. Michael K Wong17,
  18. Walter Hong18,
  19. Jeannie W Hou1,
  20. Aaron Clack1,
  21. Robert S Coffin1,
  22. Mark R Middleton19 and
  23. Bartosz Chmielowski20
  1. 1Replimune, Inc., Woburn, MA, USA
  2. 2University of Iowa, Iowa City, IA, USA
  3. 3The Clatterbridge Cancer Centre, Wirral, UK
  4. 4University of Liverpool, Liverpool, UK
  5. 5Intermountain Medical Center, Murray, UT, USA
  6. 6University of California, San Francisco, San Francisco, CA, USA
  7. 7University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA, USA
  8. 8Vall d’Hebron Institute of Oncology (VHIO) and Vall d’Hebron Hospital Medical Oncology Department, Barcelona, Spain
  9. 9West Cancer Center and Research Institute, Germantown, TN, USA
  10. 10James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA
  11. 11Gustave Roussy, Département de Médecine Oncologique, Villejuif, France
  12. 12Leeds Institute of Medical Research at St. James, University of Leeds, Leeds, UK
  13. 13Duke Cancer Institute, Duke University, Durham, NC, USA
  14. 14Division of Hematology-Oncology, University of Cincinnati, Cincinnati, OH, USA
  15. 15West German Cancer Center, University Hospital Essen, Essen, Germany
  16. 16The T.W. Lewis Melanoma Center of Excellence, Banner MD Anderson Cancer Center at Banner Gateway Medical Center, Gilbert, AZ, USA
  17. 17The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  18. 18Replimune, Woburn, MA, USA
  19. 19Churchill Hospital and the University of Oxford, Oxford, UK
  20. 20University of California Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background RP1 is an HSV-1-based oncolytic immunotherapy expressing GM-CSF and the fusogenic GALV-GP-R- protein. We present 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 Patients received RP1 via intratumoral injection into superficial or deep, including visceral, lesions. Nivolumab was given at 240mg Q2W for 4 months, then 480mg Q4W for 20 months from the second dose of RP1. Blood, urine, oral mucosa/saliva, swab samples, and injection-site dressings were collected at various timepoints on the study. Samples were assessed for the presence of RP1 DNA by an RP1-specific qPCR assay; any swab samples positive for RP1 DNA were further tested for the presence of live virus (TCID50 assay).

Results RP1 DNA was detected in blood of 37/87 (42.5%) patients and 134/791 (16.9%) samples during treatment cycles 1–8. The highest levels of RP1 DNA were in blood 6h post-injection and diminished thereafter. RP1 DNA detection in urine was minimal, with 5/86 (5.8%) patients and 8/894 (0.9%) samples testing positive. Most patients (50/87 [57.5%]) and 260/914 (28.4%) samples had RP1 DNA on the surface of injected lesions sometime during treatment. The incidence of RP1 DNA from dressings was lower than that from the injection site (18/68 [26.5%] patients; 43/525 [8.2%] samples), indicating that dressings act as a barrier to RP1 DNA. We found no live virus, per TCID50, from RP1 DNA-positive injection sites and injection-site dressings. RP1 DNA was rarely detected in oral mucosa, and mostly at low levels (15/87 [17.2%] patients; 18/931 [1.9%] samples). During follow-ups, RP1 DNA was only detected on the surface of injected lesions, with 4/56 (7.1%) and 3/42 (7.1%) patients testing positive for RP1 DNA at 30 and 60 days, respectively, after the last RP1 injection. To date, no RP1 DNA has been detected in swab samples from lesions that may be of potentially herpetic origin. There have been no reports of herpetic infection in patients’ caregivers or study staff.

Conclusions RP1 DNA was primarily detected on the surface of injected lesions, with dressings appearing to serve as a protective barrier against potential RP1 DNA dissemination. Importantly, there was no evidence of live virus following culture of qPCR-positive samples, and no reported cases of transmission or confirmed herpetic infection. These findings suggest that the risk of infection and transmission of RP1 to patients and caregivers is minimal.

Trial Registration; NCT03767348

Ethics Approval The study was conducted in accordance with the ethical principles originating from the Declaration of Helsinki and was approved by the Institutional Review Board/Ethics Committee at each participating site. Written informed consent was obtained from all patients prior to the conduct of any study-related procedures.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See

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