Danny Rischin1, Marta Gil-Martin2, Antonio González-Martin3, Irene Braña4, June Y Hou5, Daniel Cho6, Gerald S Falchook7, Silvia Formenti8, Salma Jabbour9, Kathleen Moore10, Aung Naing11, Kyriakos P Papadopoulos12, Joaquina Baranda13, Wen Fury14, Minjie Feng15, Elizabeth Stankevich14, Jingjin Li15, N Alice Yama-Dang14, Suk-Young Yoo15, Israel Lowy14, Melissa Mathias14, Matthew G Fury14. 1. Department of Medical Oncology, Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, Australia. Electronic address: Danny.Rischin@petermac.org. 2. Institut Català d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain. 3. Clinica Universidad de Navarra, Madrid, Spain. 4. Medical Oncology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. 5. Division of Gynecologic Oncology, Columbia University Medical Center, New York, NY, USA. 6. Perlmutter Cancer Center at NYU Langone Medical Center, New York, NY, USA. 7. Sarah Cannon Research Institute at HealthONE, Denver, CO, USA. 8. Department of Radiation Oncology, Weill Cornell Medicine, New York, NY, USA. 9. Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA. 10. Stephenson Cancer Center at the University of Oklahoma Health Sciences Center/Sarah Cannon Research Institute, Oklahoma City, OK, USA. 11. Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 12. START, San Antonio, TX, USA. 13. Early Phase Program Clinical Research Center, University of Kansas Cancer Center, Fairway, KS, USA. 14. Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA. 15. Regeneron Pharmaceuticals, Inc., Basking Ridge, NJ, USA.
Abstract
OBJECTIVES: To characterize the safety, tolerability, and anti-tumor activity of cemiplimab as monotherapy or in combination with hypofractionated radiation therapy (hfRT) in patients with recurrent or metastatic cervical cancer. To determine the association between histology and programmed death-ligand 1 (PD-L1) expression. METHODS: In non-randomized phase I expansion cohorts, patients (squamous or non-squamous histology) received cemiplimab 3 mg/kg intravenously every 2 weeks for 48 weeks, either alone (monotherapy cohort) or with hfRT during week 2 (combination cohort). Due to insufficient tissue material, PD-L1 protein expression was evaluated in commercially purchased samples and mRNA expression levels were analyzed from The Cancer Genome Atlas (TCGA). RESULTS: Twenty patients enrolled in both cohorts in total; 10 had squamous histology. The most common adverse events of any grade were diarrhea, fatigue, and hypokalemia, occurring in 35%, 25%, and 25%, respectively. Objective response rate was 10% in each cohort; responders had squamous histology. Duration of response was 11.2 months and 6.4 months for the responder in the monotherapy and combination cohort, respectively. Irradiated lesions were not included in the response assessments. In separate archived specimens (N = 155), PD-L1 protein expression in tumor and immune cells was negative (<1%) more commonly in adenocarcinoma than in squamous tumors. PD-L1 mRNA levels were lower in adenocarcinoma than squamous cell tumors (1.2 vs 5.0 mean transcripts per million, respectively) in TCGA. CONCLUSIONS: Cemiplimab has activity in cervical squamous cell carcinoma. The phase I results, combined with results from other anti-PD-1 trials in cervical cancer and our biomarker analyses have informed the design of the ongoing phase III trial, with the primary overall survival hierarchical analyses being done first in patients with squamous histology.
OBJECTIVES: To characterize the safety, tolerability, and anti-tumor activity of cemiplimab as monotherapy or in combination with hypofractionated radiation therapy (hfRT) in patients with recurrent or metastatic cervical cancer. To determine the association between histology and programmed death-ligand 1 (PD-L1) expression. METHODS: In non-randomized phase I expansion cohorts, patients (squamous or non-squamous histology) received cemiplimab 3 mg/kg intravenously every 2 weeks for 48 weeks, either alone (monotherapy cohort) or with hfRT during week 2 (combination cohort). Due to insufficient tissue material, PD-L1 protein expression was evaluated in commercially purchased samples and mRNA expression levels were analyzed from The Cancer Genome Atlas (TCGA). RESULTS: Twenty patients enrolled in both cohorts in total; 10 had squamous histology. The most common adverse events of any grade were diarrhea, fatigue, and hypokalemia, occurring in 35%, 25%, and 25%, respectively. Objective response rate was 10% in each cohort; responders had squamous histology. Duration of response was 11.2 months and 6.4 months for the responder in the monotherapy and combination cohort, respectively. Irradiated lesions were not included in the response assessments. In separate archived specimens (N = 155), PD-L1 protein expression in tumor and immune cells was negative (<1%) more commonly in adenocarcinoma than in squamous tumors. PD-L1 mRNA levels were lower in adenocarcinoma than squamous cell tumors (1.2 vs 5.0 mean transcripts per million, respectively) in TCGA. CONCLUSIONS:Cemiplimab has activity in cervical squamous cell carcinoma. The phase I results, combined with results from other anti-PD-1 trials in cervical cancer and our biomarker analyses have informed the design of the ongoing phase III trial, with the primary overall survival hierarchical analyses being done first in patients with squamous histology.
Authors: Katrien Vandecasteele; Hannelore G Denys; Emiel A De Jaeghere; Sandra Tuyaerts; An M T Van Nuffel; Ann Belmans; Kris Bogaerts; Regina Baiden-Amissah; Lien Lippens; Peter Vuylsteke; Stéphanie Henry; Xuan Bich Trinh; Peter A van Dam; Sandrine Aspeslagh; Alex De Caluwé; Eline Naert; Diether Lambrechts; An Hendrix; Olivier De Wever; Koen K Van de Vijver; Frédéric Amant Journal: Cancer Immunol Immunother Date: 2022-08-12 Impact factor: 6.630