@article {Rischine000775, author = {Danny Rischin and Michael R Migden and Annette M Lim and Chrysalyne D Schmults and Nikhil I Khushalani and Brett G M Hughes and Dirk Schadendorf and Lara A Dunn and Leonel Hernandez-Aya and Anne Lynn S Chang and Badri Modi and Axel Hauschild and Claas Ulrich and Thomas Eigentler and Brian Stein and Anna C Pavlick and Jessica L Geiger and Ralf Gutzmer and Murad Alam and Emmanuel Okoye and Melissa Mathias and Vladimir Jankovic and Elizabeth Stankevich and Jocelyn Booth and Siyu Li and Israel Lowy and Matthew G Fury and Alexander Guminski}, title = {Phase 2 study of cemiplimab in patients with metastatic cutaneous squamous cell carcinoma: primary analysis of fixed-dosing, long-term outcome of weight-based dosing}, volume = {8}, number = {1}, elocation-id = {e000775}, year = {2020}, doi = {10.1136/jitc-2020-000775}, publisher = {BMJ Specialist Journals}, abstract = {Background Cemiplimab, a high-affinity, potent human immunoglobulin G4 monoclonal antibody to programmed cell death-1 demonstrated antitumor activity in a Phase 1 advanced cutaneous squamous cell carcinoma (CSCC) expansion cohort (NCT02383212) and the pivotal Phase 2 study (NCT02760498). Here we report the primary analysis of fixed dose cemiplimab 350 mg intravenously every 3 weeks (Q3W) (Group 3) and provide a longer-term update after the primary analysis of weight-based cemiplimab 3 mg/kg intravenously every 2 weeks (Q2W) (Group 1) among metastatic CSCC (mCSCC) patients in the pivotal study (NCT02760498).Methods The primary objective for each group was objective response rate (ORR) per independent central review (ICR). Secondary endpoints included ORR by investigator review (INV), duration of response (DOR) per ICR and INV, and safety and tolerability.Results For Group 3 (n=56) and Group 1 (n=59), median follow-up was 8.1 (range, 0.6 to 14.1) and 16.5 (range, 1.1 to 26.6) months, respectively. ORR per ICR was 41.1\% (95\% CI, 28.1\% to 55.0\%) in Group 3, 49.2\% (95\% CI, 35.9\% to 62.5\%) in Group 1, and 45.2\% (95\% CI, 35.9\% to 54.8\%) in both groups combined. Per ICR, Kaplan{\textendash}Meier estimate for DOR at 8 months was 95.0\% (95\% CI, 69.5\% to 99. 3\%) in responding patients in Group 3, and at 12 months was 88.9\% (95\% CI, 69.3\% to 96.3\%) in responding patients in Group 1. Per INV, ORR was 51.8\% (95\% CI, 38.0\% to 65.3\%) in Group 3, 49.2\% (95\% CI, 35.9\% to 62.5\%) in Group 1, and 50.4\% (95\% CI, 41.0\% to 59.9\%) in both groups combined. Overall, the most common adverse events regardless of attribution were fatigue (27.0\%) and diarrhea (23.5\%).Conclusion In patients with mCSCC, cemiplimab 350 mg intravenously Q3W produced substantial antitumor activity with durable response and an acceptable safety profile. Follow-up data of cemiplimab 3 mg/kg intravenously Q2W demonstrate ongoing durability of responses.Trial registration number Clinicaltrials.gov, NCT02760498. Registered May 3, 2016, https://clinicaltrials.gov/ct2/show/NCT02760498}, URL = {https://jitc.bmj.com/content/8/1/e000775}, eprint = {https://jitc.bmj.com/content/8/1/e000775.full.pdf}, journal = {Journal for ImmunoTherapy of Cancer} }