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547 CERPASS: A randomized, controlled, open-label, phase 2 study of cemiplimab ± RP1 in patients with advanced cutaneous squamous cell carcinoma
  1. Andrew Haydon1,
  2. Muhammad Alamgeer2,
  3. Daniel Brungs3,
  4. Frances Collichio4,
  5. Nikhil Khushalani5,
  6. Dimitrios Colevas6,
  7. Danny Rischin7,
  8. Ragini Kudchadkar8,
  9. Wanxing Chai-Ho9,
  10. Gregory Daniels10,
  11. Jose Lutzky11,
  12. Jenny Lee12,
  13. Samantha Bowyer13,
  14. Michael Migden14,
  15. Ann Silk15,
  16. Celeste Lebbe16,
  17. Jean-jaques Grob17,
  18. Ignacio Melero18,
  19. Piyush Sheladia19,
  20. Praveen Bommareddy19,
  21. Shui He19,
  22. Claudia Andreu-Vieyra19,
  23. Matthew Fury20 and
  24. Andrew Hill21
  1. 1Alfred Hospital, Melbourne, Australia
  2. 2Monash Medical Centre, Clayton, Australia
  3. 3Southern Medical Day Care Centre, Wollongong, Australia
  4. 4Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA
  5. 5Moffitt Cancer Center, Tampa, FL, USA
  6. 6Stanford University School of Medicine, Stanford, CA, USA
  7. 7Peter MacCallum Cancer Center, East Melbourne, Australia
  8. 8Emory University, Atlanta, GA, USA
  9. 9University of California, Los Angeles, Los Angeles, USA
  10. 10UC San Diego, La Jolla, CA, USA
  11. 11University of Miami, Miami, FL, USA
  12. 12Chris O’Brien Lifehouse, Camperdown, Australia
  13. 13Sir Charles Gairdner Hospital, Nedlands, Australia
  14. 14MD Anderson Cancer Center, Houston, TX, USA
  15. 15Harvard Medical School, Boston, MA, USA
  16. 16Université de Paris, Paris, France
  17. 17Hôpital de la Timone Service de Dermatol, Marseille, France
  18. 18Universidad de Navarra, Navarra, Spain
  19. 19Replimune, Woburn, USA
  20. 20Regeneron, Tarrytown, NY, USA
  21. 21Tasman Health Care, Southport, Australia


Background The prognosis for advanced and metastatic cutaneous squamous cell carcinoma (CSCC) remains poor for many patients with the disease despite approval of the anti-PD1 antibodies cemiplimab and pembrolizumab.1 2 RP1 is an oncolytic virus (HSV-1) that expresses a fusogenic glycoprotein (GALV-GP R-) and granulocyte macrophage colony stimulating factor (GM-CSF). In preclinical studies, RP1 induced immunogenic tumor cell death and provided potent systemic anti-tumor activity, which is further improved by combining anti-PD-1 therapy.3 Preliminary results from IGNYTE, a phase I/II clinical study of RP1 in combination with nivolumab showed a high rate of deep and durable responses in patients (pts) with CSCC.4 The objective of this trial is to evaluate the safety and efficacy of cemiplimab + RP1 versus cemiplimab alone in advanced CSCC.

Methods This global, multicenter, randomized phase 2 study is enrolling pts with metastatic or unresectable, locally advanced CSCC who are not candidates for/refuse surgery and/or radiotherapy. Key eligibility criteria include no prior treatment with anti-PD1/PD-L1 antibodies or oncolytic viruses. The clinical trial will enroll approximately 180 pts from centers in the EU, Australia, Canada and USA. Pts will be randomized in a 2:1 ratio favoring the RP1 + cemiplimab arm. Pts will receive 350 mg of cemiplimab intravenously (IV) Q3W for up to 108 weeks. In the RP1 + cemiplimab arm, RP1 will be injected intratumorally at a starting RP1 dose of 1 × 10^6 plaque forming units (PFU)/mL alone, followed by up to 7 doses of RP1 at 1 × 10^7 PFU/mL Q3W together with cemiplimab. Pts in the combination arm may receive up to 8 additional RP1 doses. No crossover will be allowed. Pts will be stratified by disease status and prior systemic therapy. Tumor assessments will be performed every 9 weeks. Primary endpoints are overall response rate and complete response rate by blinded independent review. Secondary endpoints include safety, progression free survival, duration of response and overall survival. Exploratory endpoints include viral shedding and biodistribution, and immune biomarker analyses. This trial is currently enrolling pts.

Trial Registration NCT04050436


  1. Migden MR, Rischin D, Schmults CD, Guminski A, Hauschild A, Lewis KD, Chung CH, Hernandez-Aya L, Lim AM, Chang ALS, Rabinowits G, Thai AA, Dunn LA, Hughes BGM, Khushalani NI, Modi B, Schadendorf D, Gao B, Seebach F, Li S, Li J, Mathias M, Booth J, Mohan K, Stankevich E, Babiker HM, Brana I, Gil-Martin M, Homsi J, Johnson ML, Moreno V, Niu J, Owonikoko TK, Papadopoulos KP, Yancopoulos GD, Lowy I, Fury MG. PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. N Engl J Med 2018;379(4):341–351.

  2. Grob JJ, Gonzalez R, Basset-Seguin N, Vornicova O, Schachter J, Joshi A, Meyer N, Grange F, Piulats JM, Bauman JR, Zhang P, Gumuscu B, Swaby RF, Hughes BGM. Pembrolizumab monotherapy for recurrent or metastatic cutaneous squamous cell carcinoma: a single-arm phase II trial (KEYNOTE-629). J Clin Oncol 2020;38(25):2916–2925.

  3. 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.

  4. Middleton M, Aroldi F, Sacco J, Milhem M, Curti B, VanderWalde A, Baum S, Samson A, Pavlick A, Chesney J, Niu J, Rhodes T, Bowles T, Conry R, Olsson-Brown A, Earl Laux D, Kaufman H, Bommareddy P, Deterding A, Samakoglu S, Coffin R, Harrington K. 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. J Immunother Cancer 2020; 8 (3).

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

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