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Regular and Young Investigator Award Abstracts
Clinical Trials In Progress
506 IGNYTE: an open-label, multicenter, phase 1/2 (Ph 1/2) clinical trial of RP1 ± nivolumab in patients with advanced solid tumors
Free
  1. Mark Middleton1,
  2. Mohammed Milhem2,
  3. Francesca Aroldi3,
  4. Joseph Sacco4,
  5. Ari VanderWalde5,
  6. Scott Baum5,
  7. Adel Samson6,
  8. Jason Chesney7,
  9. Jiaxin Niu8,
  10. Terence Rhodes9,
  11. Tawnya Bowles9,
  12. Hamid Emamekhoo10,
  13. Katy Tsai11,
  14. Gino In12,
  15. Georgia Beasley13,
  16. Bartosz Chmielowski14,
  17. Sophie Dalac-Rat15,
  18. Katharina Kahler16,
  19. Eva Muñoz17,
  20. Anna Olsson-Brown4,
  21. Praveen Bommareddy18,
  22. Lavita Menezes18,
  23. Andrea Pirzkall18,
  24. Robert Coffin18 and
  25. Kevin Harrington19
  1. 1Churchill Hospital, Oxford, UK
  2. 2Holden Comprehensive Cancer Center, Iowa City, IA, USA
  3. 3University of Oxford, Oxford, UK
  4. 4Clatterbridge Cancer Centre, Wirral, UK
  5. 5West Cancer Center and Research Institute, Germantown, TN, USA
  6. 6University of Leeds, Leeds, UK
  7. 7James Graham Brown Cancer Center, Louisville, KY, USA
  8. 8Banner MD Anderson Cancer Center, Gilbert, AZ, USA
  9. 9Intermountain Med Ctr, St. George, UT, USA
  10. 10Carbone Cancer Center, Madison, WI, USA
  11. 11Helen Diller Family Comprehensive Cancer, San Francisco, CA, USA
  12. 12Norris Comprehensive Cancer Center, Los Angeles, CA, USA
  13. 13Duke Cancer Institute, DURHAM, NC, USA
  14. 14University of California Los Angeles, Los Angeles, CA, USA
  15. 15CHU Dijon Bourgogne, Bourgogne, France
  16. 16University of Kiel, Kiel, Germany
  17. 17Vall d’Hebron Hospital, Vall D’hebron, Spain
  18. 18Replimune, Woburn, MA, USA
  19. 19The Institute of Cancer Research, London, UK

Abstract

Background RP1 is an enhanced potency oncolytic HSV-1 which expresses a fusogenic glycoprotein (GALV-GP R-) and granulocyte macrophage colony stimulating factor (GM-CSF).1 In pre-clinical studies, RP1 demonstrated potent GALV-GP R-enhanced anti-tumor activity and immunogenic cell death. This Phase 1/2 (Ph 1/2) study was designed to evaluate the safety and efficacy of RP1 ± nivolumab (nivo) in patients (pts) with advanced solid tumors, including pts whose disease failed prior anti-PD-1/PD-L1 therapy and has reported promising interim data in a number of tumor types including cutaneous squamous cell carcinoma (CSCC) and anti-PD1 failed melanoma to date.2

Methods This is a multi-center, first-in-human, open label, multi-cohort, non-randomized Ph1 study of RP1 alone and combined with nivo followed by Ph2 in combination with nivo in pts with recurrent advanced solid tumors including those that progressed after prior anti-PD-1/PD-L1 therapy. The Ph 1 monotherapy dose escalation (n=14) and RP-1 combination expansion (n=22) cohorts are fully enrolled. Approximately 260 pts are expected to be enrolled in the ongoing Ph 2 portion across five cohorts; melanoma (n=30, enrollment complete), non-melanoma skin cancer (n=45, to include 15 pts with anti-PD-1/PD-L1 failed disease), anti-PD-1 failed MSI-H/dMMR tumors (n=30), anti-PD-1/PD-L1-failed non-small-cell lung cancer (n=30) and a registration-directed cohort in anti-PD-1 failed cutaneous melanoma (n=125). Pts in the Ph 2 portion receive up to 10 mL of RP1 intratumorally into one or more superficial or deep seated/visceral lesions at the recommended Ph 2 dose (1x10^6 PFU/mL × 1 followed by 1x10^7 PFU/mL × 7, Q2W). Following the first dose of RP1, nivo (240 mg IV Q2W for 4 months then 480 mg IV Q4W for up to 2 years) is subsequently administered in combination. Pts may receive up to 8 additional doses of RP1 if they meet protocol-specified criteria. Tumor assessments are performed Q8W. The primary objectives of the Ph 2 part of the study are to assess the safety, tolerability, and overall response rate (ORR) of RP1 in combination with nivo, by independent review for the anti-PD1 failed melanoma cohort. Secondary objectives include duration of response, complete response rate, disease control rate, PFS, 1-year and 2-year survival rates. Exploratory objectives include biodistribution and shedding analysis of RP1 and biomarker studies, including analyses of tumor biopsies and blood samples. Enrollment is currently ongoing in the UK and US, with additional sites in the EU (including France and Spain) are expected to open in 2021.

Trial Registration NCT03767348

References

  1. Thomas S, Kuncheria L, Roulstone V, Kyula JN, Mansfield D, Bommareddy PK, Smith H, Kaufman HL, Harrington KJ, Coffin RS. Development of a new fusion-enhanced oncolytic immunotherapy platform based on herpes simplex virus type 1. J Immunother Cancer 2019;7(1):214.

  2. Coffin R, Astley-Sparke P, and Middleton M (2021, June 3rd). Retrieved from https://ir.replimune.com/static-files/f4fe3349-e082-4d41-94a1-106ce7e78a23

Ethics Approval The study was approved by institutional review board or the local ethics committee at each site. Informed consent was obtained from patients prior to enrollment.

https://doi.org/10.1136/jitc-2021-SITC2021.506

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