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611 Biodistribution and shedding analysis following treatment with RP1 oncolytic immunotherapy in the skin cancer patients from the IGNYTE clinical trial
  1. Mohammed Milhem1,
  2. Ari VanderWalde2,
  3. Tawnya Bowles3,
  4. Joseph Sacco4,
  5. Anna Olsson-Brown4,
  6. Jiaxin Niu5,
  7. Katy Tsai6,
  8. Jason Chesney7,
  9. Bartosz Chmielowski8,
  10. Adel Samson9,
  11. Terence Rhodes3,
  12. Gino In10,
  13. Anna Pavlick11,
  14. Trisha Wise-Draper12,
  15. Miguel Sanmamed13,
  16. Alireza Kalbasi14,
  17. Colin Love14,
  18. Aaron Clack14,
  19. Jeannie Hou14,
  20. Praveen Bommareddy14,
  21. Robert Coffin14,
  22. Mark Middleton15 and
  23. Kevin Harrington16
  1. 1Holden Comprehensive Cancer Center, Iowa City, IA, United States
  2. 2West Cancer Center and Research Institute, Germantown, TN, United States
  3. 3Intermountain Medical Center, Murray, UT, United States
  4. 4Clatterbridge Cancer Centre, Liverpool, UK
  5. 5Banner MD Anderson Cancer Center, Gilbert, AZ, United States
  6. 6Helen Diller Family Comprehensive Cancer, San Francisco, CA, United States
  7. 7James Graham Brown Cancer Center, Louisville, KY, United States
  8. 8University of California Los Angeles, Los Angeles, CA, United States
  9. 9University of Leeds, Leeds, UK
  10. 10Norris Comprehensive Cancer Center, Los Angeles, CA, United States
  11. 11Weill Cornell Medical College, New York, NY, United States
  12. 12University of Cincinnati, Cincinnati, OH, United States
  13. 13Clínica Universidad de Navarra, New Haven, CT, United States
  14. 14Replimune Inc, Woburn, MA, United States
  15. 15Churchill Hospital, Oxford, UK
  16. 16Royal Marsden NHS Foundation Trust, Sutton, UK


Background RP1 is HSV1-based oncolytic immunotherapy expressing GM-CSF and the fusogenic GALV-GP R- protein. We present biodistribution and shedding data from the melanoma (n=30) and NMSC patients (n=31) of an ongoing clinical trial of RP1 + nivolumab (nivo).

Methods RP1 was injected into lesions (106 PFU/mL, then 107 PFU/mL Q2W) for up to 8 cycles. Injected lesions were covered with occlusive dressings. Blood, urine and swabs from dressing exteriors, tumor surface, oral mucosa, and areas of suspected herpetic origin were collected. RP1 DNA presence was assessed using qPCR and infectivity by TCID50.

Results RP1 DNA was detected in blood from 32.1% patients and 11.0% of blood samples. Highest levels were detected at 6 hrs. A sub-set of patients showed continued DNA until the next injection, with kinetics indicating RP1 replication. RP1 DNA was undetectable in all urine samples. Additionally, 50.9% of patients and 22.7% of swabs were positive from injection sites, with approximately 20% of patients positive at the next injection, also indicating RP1 replication. 20.5% of patients and 6.2% of samples tested positive for RP1 DNA on the dressing exterior between 24 hrs and the next dose, at low levels compared to injection sites. RP1 DNA was detected at low levels on the oral mucosa (15.1% of patients or 1.9% of samples). During the safety follow-up period, RP1 DNA was only detected on the injected lesion surface and not other sites, with 5.5% and 3.8% of patients positive at 30 and 60 days after the last RP1 dose respectively. Swabs positive for RP1 DNA were assessed for infectious virus by TCID50, and all were negative. No RP1 DNA was detected in swabs from potentially herpetic lesions, with no reports of herpetic infection in patient’s caregivers.

Conclusions All positive samples showed only residual RP1 DNA rather than RP1 itself. RP1 DNA was detected on injected tumor surfaces at higher levels compared to other sites for up to 15 days (time of next dose), and then at diminishing levels up to 60 days from last dose. DNA levels at other sites were much lower and transient. In blood, RP1 DNA was detected in a quantity and with kinetics indicative of virus replication in a sub-set of patients, as expected based on the mechanism of action of RP1. Overall, the data suggest that the possibility of RP1 transmission to contacts is minimal, with no evidence of transmission reported.

Trial Registration NCT03767348

Ethics Approval The study was approved by the institutional review board or the local ethics committee at each participating site. Informed consent was obtained from patients before participating in the trial.

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