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422 An open-label, multicenter, phase 1/2 clinical trial of RP1, an enhanced potency oncolytic HSV, combined with nivolumab: updated results from the skin cancer cohorts
  1. Mark Middleton1,
  2. Francesca Aroldi1,
  3. Joseph Sacco2,
  4. Mohammed Milhem3,
  5. Brendan Curti4,
  6. Ari VanderWalde MBioeth5,
  7. Scott Baum5,
  8. Adel Samson6,
  9. Anna Pavlick7,
  10. Jason Chesney8,
  11. Jiaxin Niu9,
  12. Terence Rhodes10,
  13. Tawnya Bowles11,
  14. Robert Conry12,
  15. Anna Olsson-Brown2,
  16. Douglas Earl Laux3,
  17. Howard Kaufman13,
  18. Praveen Bommareddy14,
  19. Alex Deterding14,
  20. Selda Samakoglu14,
  21. Robert Coffin14 and
  22. Kevin Harrington15
  1. 1University of Oxford, Oxford, UK
  2. 2University of Liverpool, Wirral, UK
  3. 3University of Iowa, Iowa City, IA, USA
  4. 4Providence Cancer Center, Portland, OR, USA
  5. 5West Cancer Center, Germantown, TN, USA
  6. 6University of Leeds, Leeds, UK
  7. 7Laura and Isaac Perlmutter Cancer Center, New York, NY, USA
  8. 8James Graham Brown Cancer Center, Louisville, KY, USA
  9. 9Banner MD Anderson Cancer Center, Goodyear, AZ, USA
  10. 10Intermountain Med Center, St. George, UT, USA
  11. 11Intermountain Medical Center, Murray, UT, USA
  12. 12University of Alabama, Birmingham, AL, USA
  13. 13Massachusetts General Hospital, Cambridge, MA, USA
  14. 14Replimune Inc., Woburn, MA, USA
  15. 15The Institute of Cancer Research, London, UK


Background RP1 is an enhanced potency oncolytic HSV encoding a fusogenic protein (GALV-GP R-) and GM-CSF which has previously demonstrated tolerable safety and tumor regression alone and with nivolumab in patients with a number of tumor types. Updated data from the phase 1 expansion with nivolumab, melanoma phase 2 (enrollment complete) and non-melanoma skin cancer (NMSC; enrollment ongoing) cohorts will be presented (NCT03767348). Enrollment of a further 125 patient anti-PD1 refractory cutaneous melanoma cohort; and activation of a cohort of anti-PD1 refractory NSCLC is underway.

Methods Stage IIIb-IV melanoma patients for whom anti-PD-1 was indicated or who were refractory to prior anti-PD-1 alone or in combination with anti-CTLA-4, were enrolled. NMSC patients were anti-PD1 naïve. Patients received ≤8 doses of RP1 (≤10 mL/visit Q2W; first dose 106 PFU/mL then 107 PFU/mL) with nivolumab (240 mg IV Q2W for 4 months then 480 mg IV Q4W up to 2 years) from the second RP1 dose.

Results As of 24th June 2020, 36 melanoma and 16 NMSC patients had been enrolled with follow up of <1–17 months. Of the melanoma patients, 16 previously anti-PD1 treated cutaneous (8 also prior anti-CTLA-4), 8 anti-PD1 naïve cutaneous, 6 mucosal, and 6 uveal. Of the NMSC patients, 10 had squamous cell (CSCC), 3 had a basal cell, 1 had Merkel cell carcinomas, and 2 had angiosarcoma. Treatment emergent adverse events (TEAEs) remain consistent with phase 1, with RP1 side effects generally of Grade 1/2 constitutional-type symptoms, with no exacerbation of the side effects expected for nivolumab. At the data cut-off, 5 previously anti-PD1 treated (4 also anti-CTLA-4) cutaneous melanoma patients, 4 anti-PD1 naïve cutaneous melanoma patients, two mucosal melanoma patients (one anti-PD1 refractory) and one uveal melanoma patient (ipi/nivo refractory) have achieved response (WHO criteria for uveal). For NMSC, for the 13 patients with >8 weeks follow up, one of two angiosarcoma patients and seven of eight CSCC patients (5 CR) have achieved response (CSCC ORR 87.5%; CR rate 62.5%, including of uninjected visceral disease). Tumor biopsies in patients continue to routinely show immune activation, including robust recruitment of CD8+ T cells, reversal of T cell exclusion, and increased PD-L1 expression. Treatment remains ongoing, and current data will be presented.

Conclusions RP1 and nivolumab have continued to be well tolerated, with continued promising anti-tumor activity in patients with skin cancers, including those with anti-PD1 refractory and other difficult to treat melanomas, and in patients with CSCC.

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