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Phase 3 randomized COMMODORE 2 trial: Crovalimab versus eculizumab in patients with paroxysmal nocturnal hemoglobinuria naive to complement inhibition.
Röth, Alexander; He, Guangsheng; Tong, Hongyan; Lin, Zenghua; Wang, Xiaoqin; Chai-Adisaksopha, Chatree; Lee, Je-Hwan; Brodsky, Andres; Hantaweepant, Chattree; Dumagay, Teresita E; Demichelis-Gómez, Roberta; Rojnuckarin, Ponlapat; Sun, Jing; Höglund, Martin; Jang, Jun Ho; Gaya, Anna; Silva, Fernando; Obara, Naoshi; Kelly, Richard J; Beveridge, Leigh; Buatois, Simon; Chebon, Sammy; Gentile, Brittany; Lundberg, Pontus; Sreckovic, Sasha; Nishimura, Jun-Ichi; Risitano, Antonio; Han, Bing.
Afiliación
  • Röth A; Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
  • He G; Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China.
  • Tong H; Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Lin Z; Department of Hematology, Affiliated Hospital of Nantong University, Jiangsu, China.
  • Wang X; Department of Hematology, Huashan Hospital, Fudan University, Shanghai, China.
  • Chai-Adisaksopha C; Faculty of Medicine Chiang Mai University, Chiang Mai, Thailand.
  • Lee JH; Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
  • Brodsky A; Hematology Division, Hospital de Clínicas José de San Martín, University of Buenos Aires, Buenos Aires, Argentina.
  • Hantaweepant C; Faculty of Medicine Siriraj Hospital, Division of Hematology, Department of Medicine, Mahidol University, Bangkok, Thailand.
  • Dumagay TE; Division of Hematology, Department of Medicine, University of the Philippines, Philippine General Hospital, Manila, Philippines.
  • Demichelis-Gómez R; Department of Hematology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
  • Rojnuckarin P; Center of Excellence in Translational Hematology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
  • Sun J; Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • Höglund M; Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
  • Jang JH; Department of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
  • Gaya A; Hematology Department, Hospital Clínic de Barcelona, Barcelona, Spain.
  • Silva F; Hematology Department, Centro Hospitalar do Baixo Vouga, Aveiro, Portugal.
  • Obara N; Department of Hematology, University of Tsukuba Hospital, Ibaraki, Japan.
  • Kelly RJ; Division of Haematology and Immunology, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK.
  • Beveridge L; Genentech, Inc., South San Francisco, California, USA.
  • Buatois S; F. Hoffmann-La Roche Ltd, Basel, Switzerland.
  • Chebon S; F. Hoffmann-La Roche Ltd, Basel, Switzerland.
  • Gentile B; Genentech, Inc., South San Francisco, California, USA.
  • Lundberg P; F. Hoffmann-La Roche Ltd, Basel, Switzerland.
  • Sreckovic S; Genentech, Inc., South San Francisco, California, USA.
  • Nishimura JI; Osaka University Graduate School of Medicine, Osaka, Japan.
  • Risitano A; Hematology and BMT Unit, AORN San Giuseppe Moscati, Avellino, Italy.
  • Han B; Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Peking, China.
Am J Hematol ; 99(9): 1768-1777, 2024 Sep.
Article en En | MEDLINE | ID: mdl-38884175
ABSTRACT
Crovalimab is a novel C5 complement inhibitor that enables rapid and sustained C5 inhibition with subcutaneous, low-volume self-administration every 4 weeks. COMMODORE 2 (NCT04434092) is a global, randomized, open-label, multicenter, phase 3 trial evaluating the non-inferiority of crovalimab versus eculizumab in patients with paroxysmal nocturnal hemoglobinuria not previously treated with C5 inhibition. C5 inhibitor-naive patients with lactate dehydrogenase (LDH) ≥2 × upper limit of normal (ULN) were randomized 21 to crovalimab or eculizumab. Co-primary efficacy endpoints were proportion of patients with hemolysis control (centrally assessed LDH ≤1.5 × ULN) and proportion with transfusion avoidance. Secondary efficacy endpoints were proportions of patients with breakthrough hemolysis, stabilized hemoglobin, and change in FACIT-Fatigue score. The primary treatment period was 24 weeks. Two hundred and four patients were randomized (135 crovalimab; 69 eculizumab). Crovalimab was non-inferior to eculizumab in the co-primary endpoints of hemolysis control (79.3% vs. 79.0%; odds ratio, 1.0 [95% CI, 0.6, 1.8]) and transfusion avoidance (65.7% vs. 68.1%; weighted difference, -2.8 [-15.7, 11.1]), and in the secondary efficacy endpoints of breakthrough hemolysis (10.4% vs. 14.5%; weighted difference, -3.9 [-14.8, 5.3]) and hemoglobin stabilization (63.4% vs. 60.9%; weighted difference, 2.2 [-11.4, 16.3]). A clinically meaningful improvement in FACIT-Fatigue score occurred in both arms. Complete terminal complement activity inhibition was generally maintained with crovalimab. The safety profiles of crovalimab and eculizumab were similar with no meningococcal infections. Most patients who switched from eculizumab to crovalimab after the primary treatment period preferred crovalimab. These data demonstrate the positive benefit-risk profile of crovalimab.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inactivadores del Complemento / Anticuerpos Monoclonales Humanizados / Hemoglobinuria Paroxística Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Am J Hematol Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inactivadores del Complemento / Anticuerpos Monoclonales Humanizados / Hemoglobinuria Paroxística Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Am J Hematol Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos