Dose exploration results from Phase 1 study of cemiplimab, a human monoclonal programmed death (PD)-1 antibody, in Japanese patients with advanced malignancies
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Published:2020-11-04
Issue:1
Volume:87
Page:53-64
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ISSN:0344-5704
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Container-title:Cancer Chemotherapy and Pharmacology
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language:en
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Short-container-title:Cancer Chemother Pharmacol
Author:
Kitano ShigehisaORCID, Shimizu Toshio, Koyama Takafumi, Ebata Takahiro, Iwasa Satoru, Kondo Shunsuke, Shimomura Akihiko, Fujiwara Yutaka, Yamamoto Noboru, Paccaly Anne, Li Siyu, Rietschel Petra, Sims Tasha
Abstract
Abstract
Purpose
Part 1 of this two-part, open-label, Phase 1 study (NCT03233139) assessed the safety, tolerability, pharmacokinetics, immunogenicity, and clinical activity of cemiplimab in Japanese patients with advanced malignancies.
Methods
Patients received cemiplimab 250 mg (n = 6) or 350 mg (n = 7) every 3 weeks intravenously for up to 108 weeks in Part 1. Tumor responses were assessed by investigators every 9 weeks using the Response Evaluation Criteria in Solid Tumors version 1.1.
Results
Of 13 patients enrolled, median age was 62 years (range 33–75) and eight patients were female. Median duration of cemiplimab exposure was 13.1 weeks (range 3.0‒113.6). At the time of data cut-off, 11 patients (84.6%) had discontinued treatment (majority due to disease progression: n = 8, 61.5%). The most common treatment-emergent adverse events (TEAEs) of any grade were contact dermatitis, rash, and viral upper respiratory tract infection (each n = 3, 23.1%). Five grade ≥ 3 TEAEs were reported in four patients: autoimmune colitis, dehydration, hyponatremia, hypophosphatemia, and muscular weakness. No dose-limiting toxicities were reported and no TEAEs led to death. Cemiplimab concentrations in serum were consistent with previously reported pharmacokinetic characteristics of cemiplimab. No anti-drug antibodies were detected in serum. Objective response rate [ORR; complete response + partial response (PR)] was 30.8% (four PR) and disease control rate [ORR + stable disease (SD)] was 46.2% (6/13; two SD).
Conclusion
Cemiplimab exhibited antitumor activity in Japanese patients with advanced malignancies. The safety profile was comparable to those previously reported for cemiplimab and other PD-1 inhibitors.
Trial registration
NCT03233139 at ClinicalTrials.gov.
Graphic abstract
Funder
The study was funded by Regeneron Pharmaceuticals, Inc. and Sanofi.
Publisher
Springer Science and Business Media LLC
Subject
Pharmacology (medical),Cancer Research,Pharmacology,Toxicology,Oncology
Reference37 articles.
1. Burova E, Hermann A, Waite J, Potocky T, Lai VSH, Liu M, Allbritton O, Woodruff A, Wu Q, D’Orvilliers A, Garnova E, Rafique A, Poueymirou W, Martin J, Huang T, Skokos D, Kantrowitz J, Popke J, Mohrs M, MacDonald D, Ioffe E, Olson W, Lowy I, Murphy A, Thurston G (2017) Characterization of the anti-PD-1 antibody REGN2810 and its antitumor activity in human PD-1 knock-in mice. Mol Cancer Ther 16(5):861–870. https://doi.org/10.1158/1535-7163.MCT-16-0665 2. 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 (2018) PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. N Engl J Med 379(4):341–351. https://doi.org/10.1056/NEJMoa1805131 3. Davda J, Declerck P, Hu-Lieskovan S, Hickling TP, Jacobs IA, Chou J, Salek-Ardakani S, Kraynov E (2019) Immunogenicity of immunomodulatory, antibody-based, oncology therapeutics. J Immunother Cancer 7(1):105. https://doi.org/10.1186/s40425-019-0586-0 4. Papadopoulos KP, Johnson ML, Lockhart AC, Moore K, Falchook GS, Formenti SC, Naing A, Carvajal RD, Rosen LS, Weiss GJ, Leidner RS, Li J, Paccaly A, Feng M, Stankevich E, Lowy I, Fury MG, Crittenden MR (2020) First-in-human study of cemiplimab alone or in combination with radiotherapy and/or low-dose cyclophosphamide in patients with advanced malignancies. Clin Cancer Res 26(5):1025–1033. https://doi.org/10.1158/1078-0432.CCR-19-2609 5. Moreno Garcia V, Calvo E, Olmedo Garcia ME, Gil Martin M, Aljumaily R, Papadopoulos KP, Rosen LS, Rietschel P, Mohan KK, Li J (2019) Tolerability and antitumor activity of cemiplimab, a human monoclonal anti-PD-1, in patients with non-small cell lung cancer (NSCLC): interim data from phase 1 dose escalation and NSCLC expansion cohort. J Clin Oncol 37(suppl 8; abstr 116). https://doi.org/10.1200/JCO.2019.37.8_suppl.116
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