Article Text

Download PDFPDF

774 NeoPOWER: A phase II study of neoadjuvant PD-1 blockade with cemiplimab in high risk localized, locally recurrent and regionally advanced cutaneous squamous cell carcinoma
  1. Gino K In1,
  2. Sunandana Chandra2,
  3. Jeffrey Sosman2,
  4. Erin Barrett3,
  5. Ashley Wysong3,
  6. Alissa Marr3,
  7. Joshua Mammen3,
  8. Jacob Thomas1,
  9. Thomas Won1,
  10. Anisa Sandin1,
  11. Sophia Marmolejo1,
  12. Andrew Zeng1,
  13. Fumito Ito4,
  14. Niels Kokot5,
  15. Mark Swanson5,
  16. Daniel Kwon5,
  17. Denice Tsao-Wei1,6,
  18. Susan Groshen1,
  19. Kevin Kelly6,
  20. Hugo Lara Martinez1,
  21. Andy Sherrod5,
  22. Brittney Declerck5,
  23. Gene Kim5,
  24. David Peng5 and
  25. Jenny C Hu5
  1. 1University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA, USA
  2. 2Northwestern University, Chicago, IL, USA
  3. 3University of Nebraska Medical Center, Omaha, NE, USA
  4. 4Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
  5. 5University of Southern California, Keck School of Medicine, Los Angeles, CA, USA
  6. 6University of Southern California, 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 PD-1 blockade achieves response rates of ~50% in patients with unresectable or metastatic cutaneous squamous cell carcinoma (CSCC); furthermore, responses are durable lasting greater than 6 months in 60% of patients. Given the efficacy of PD-1 therapy in treating CSCC, we hypothesize that the use of 3 cycles of neoadjuvant cemiplimab therapy may help not only achieve improved surgical cure but also induce long-term control for this patient population, and with a reasonable toxicity profile. This study seeks to evaluate PD-1 therapy in the neoadjuvant setting for patients with resectable CSCC, including those with high-risk localized disease, locally recurrent, and regionally advanced disease.

Methods NeoPOWER (NCT04315701) is a phase 2, multicenter, open-label study of neoadjuvant cemiplimab in patients with resectable CSCC. A total of 34 patients will be enrolled. Eligible patients must have measurable and resectable CSCC, according to one of the following categories: 1) high-risk localized CSCC, defined by clinical risk factors including tumor diameter >2.0 cm, tumors >1.0 cm in high risk locations, and/or pathological risk factors including depth>6mm, poorly differentiated histology, or perineural invasion, 2) locally recurrent CSCC that has failed prior surgery or radiation, or 3) regionally advanced CSCC, including in-transit, subcutaneous or lymph node metastases. Patients with unresectable or distant metastatic disease are not eligible. Patients will be treated with cemiplimab 350 mg IV every 3 weeks for 3 cycles, then will undergo surgery with curative intent; one additional cycle of cemiplimab may be administered prior to surgery, per investigator discretion. All patients will require baseline imaging prior to therapy, and again prior to surgical resection. The primary efficacy endpoint will be pathological partial response (PRR), defined as less than 50% viable tumor cells on pathologic evaluation of resected surgical specimens. Secondary endpoints include pathologic complete response (PCR), RECIST 1.1 objective response rate (ORR) at 9 weeks, progression-free survival (PFS) at 12 months, and toxicity. This study will employ a Simon two-stage design with an accrual goal of 34 patients, to provide 80% power to detect a targeted PPR of 40% for neoadjuvant cemiplimab; the first stage will include 13 patients, and if 4 or more PPR are observed, then the second stage will allow for an additional 21 patients. Correlative biomarkers will include analyze CD8+ T-cell infiltration, PD-L1 expression and tumor mutational burden (TMB), among others. As of June 2023, 12 of 34 planned subjects have been enrolled.

Ethics Approval The study was approved by the institutional review board at each site and was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines of the International Conference on Harmonization. All patients provided written informed consent.

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

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.