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
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 rep...
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BMJ Publishing Group
2020-05-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/8/1/e000775.full |
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| author | Dirk Schadendorf Ralf Gutzmer Thomas Eigentler Israel Lowy Vladimir Jankovic Elizabeth Stankevich Anna C Pavlick Danny Rischin Michael R Migden Annette M Lim Chrysalyne D Schmults Nikhil I Khushalani Brett G M Hughes Lara A Dunn Leonel Hernandez-Aya Anne Lynn S Chang Badri Modi Axel Hauschild Claas Ulrich Brian Stein Jessica L Geiger Murad Alam Emmanuel Okoye Melissa Mathias Jocelyn Booth Siyu Li Matthew G Fury Alexander Guminski |
| author_facet | Dirk Schadendorf Ralf Gutzmer Thomas Eigentler Israel Lowy Vladimir Jankovic Elizabeth Stankevich Anna C Pavlick Danny Rischin Michael R Migden Annette M Lim Chrysalyne D Schmults Nikhil I Khushalani Brett G M Hughes Lara A Dunn Leonel Hernandez-Aya Anne Lynn S Chang Badri Modi Axel Hauschild Claas Ulrich Brian Stein Jessica L Geiger Murad Alam Emmanuel Okoye Melissa Mathias Jocelyn Booth Siyu Li Matthew G Fury Alexander Guminski |
| author_sort | Dirk Schadendorf |
| collection | DOAJ |
| description | 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–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 |
| format | Article |
| id | doaj-art-a6c7cd3cc4a44c238d9eeebc62a5df0f |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2020-05-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-a6c7cd3cc4a44c238d9eeebc62a5df0f2025-08-20T02:13:19ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-05-018110.1136/jitc-2020-000775Phase 2 study of cemiplimab in patients with metastatic cutaneous squamous cell carcinoma: primary analysis of fixed-dosing, long-term outcome of weight-based dosingDirk Schadendorf0Ralf Gutzmer1Thomas Eigentler2Israel Lowy3Vladimir Jankovic4Elizabeth Stankevich5Anna C Pavlick6Danny Rischin7Michael R Migden8Annette M Lim9Chrysalyne D Schmults10Nikhil I Khushalani11Brett G M Hughes12Lara A Dunn13Leonel Hernandez-Aya14Anne Lynn S Chang15Badri Modi16Axel Hauschild17Claas Ulrich18Brian Stein19Jessica L Geiger20Murad Alam21Emmanuel Okoye22Melissa Mathias23Jocelyn Booth24Siyu Li25Matthew G Fury26Alexander Guminski27University Hospital of Essen, University Duisburg-Essen, NCT-West, Essen Campus, German Cancer Consortium, Partner Site Essen & University Alliance Ruhr, One Health Research Centre, Essen, GermanyDepartment of Dermatology, Muelenkreiskliniken Minden and Ruhr University Bochum, Minden, GermanyCharité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Dermatology, Venereology and Allergology, Berlin, GermanyRegeneron Pharmaceuticals, Inc, Tarrytown, New York, USAAff3 Celgene Cellular Therapeutics Warren NJ USARegeneron Pharmaceuticals, Tarrytown, New York, USA1 Weill Cornell Medicine, New York, New York, USADepartment of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, AustraliaDepartments of Dermatology and Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas, USADepartment of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, AustraliaDermatologic Surgery, Mohs Micrographic Surgery Center, Dana-Farber Cancer Institute, Boston, Massachusetts, USADepartment of Cutaneous Oncology, Moffitt Cancer Center, Tampa, Florida, USARoyal Brisbane and Women`s Hospital and University of Queensland, Brisbane, Queensland, Australia13Memorial Sloan Kettering Cancer Center, New York, NY, USAUniversity of Miami Miller School of Medicine, Miami, Florida, USADepartment of Dermatology, Stanford University School of Medicine, Redwood City, California, USA10 Division of Dermatology, City of Hope, Duarte, California, USADepartment of Dermatology, Schleswig-Holstein University Hospital, Kiel, Germany12 Skin Cancer Centre, Charité Universitätsmedizin Berlin, Berlin, GermanyICON Cancer Centre, Adelaide, South Australia, Australia9The Cleveland Clinic Foundation, Cleveland, OH, USADermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USARegeneron Pharmaceuticals, Inc, Tarrytown, New York, USA20 Regeneron Pharmaceuticals, Inc, Tarrytown, New York, USARegeneron Pharmaceuticals, Inc, Tarrytown, New York, USADepartment of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, ChinaRegeneron Pharmaceuticals, Inc, Tarrytown, New York, USADepartment of Medical Oncology, Royal North Shore Hospital, St Leonards, New South Wales, AustraliaBackground 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–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/NCT02760498https://jitc.bmj.com/content/8/1/e000775.full |
| spellingShingle | Dirk Schadendorf Ralf Gutzmer Thomas Eigentler Israel Lowy Vladimir Jankovic Elizabeth Stankevich Anna C Pavlick Danny Rischin Michael R Migden Annette M Lim Chrysalyne D Schmults Nikhil I Khushalani Brett G M Hughes Lara A Dunn Leonel Hernandez-Aya Anne Lynn S Chang Badri Modi Axel Hauschild Claas Ulrich Brian Stein Jessica L Geiger Murad Alam Emmanuel Okoye Melissa Mathias Jocelyn Booth Siyu Li Matthew G Fury Alexander Guminski 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 Journal for ImmunoTherapy of Cancer |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | https://jitc.bmj.com/content/8/1/e000775.full |
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