Oren Smaletz1, Maria D P E Diz2, Claudio C do Carmo3, Jorge Sabbaga4, Geraldo F Cunha-Junior5, Sergio J Azevedo6, Fernando C Maluf7, Carlos H Barrios8, Ronaldo L Costa9, Ana G Fontana10, Vivian Madrigal10, Alberto J Wainstein11, Fernanda P Yeda11, Venâncio A Alves12, Ana M Moro13, Roberto Blasbalg14, Andrew M Scott15, Eric W Hoffman15. 1. Hospital Israelita Albert Einstein, Avenida Albert Einstein, 627, São Paulo, SP 05651-901, Brazil. Electronic address: osmaletz@einstein.br. 2. Instituto do Câncer do Estado de São Paulo - University of São Paulo School of Medicine. Avenida Doutor Arnaldo, 251, São Paulo, SP 01255-000, Brazil. 3. Instituto Nacional do Câncer José Alencar Gomes da Silva, Praça Cruz Vermelha, 23, Rio de Janeiro, RJ 20230-130, Brazil. 4. Hospital Alemão Oswaldo Cruz, Rua João Julião, 331, São Paulo, SP 01323-903, Brazil. 5. Hospital da Baleia, Rua Juramento, 1464, Belo Horizonte, MG 30285-000, Brazil. 6. Hospital de Clinicas de Porto Alegre, Rua Ramiro Barcelos, 2350, Porto Alegre, RS 90035-903, Brazil. 7. Hospital Sírio-Libanês, Rua Dona Adma Jafet, 91, São Paulo, SP 01308-050, Brazil. 8. Pontifícia Universidade Católica do Rio Grande do Sul School of Medicine, Rua Padre Chagas 66, 203, Porto Alegre, RS 90570-080, Brazil. 9. Instituto Brasileiro de Controle do Câncer, Av. Alcântara Machado, 2576, São Paulo, SP 03102-002, Brazil. 10. Recepta Biopharma, Rua Tabapuã, 1123, São Paulo, SP 04533-014, Brazil. 11. Biocâncer Centro de Pesquisa Clínica SA, Avenida Bernardo Monteiro, 890, Belo Horizonte, MG 30150-281, Brazil. 12. Department of Pathology, University of São Paulo School of Medicine, Av. Dr. Arnaldo, 455, São Paulo, SP 01246-903, Brazil. 13. Laboratório Biofármacos em Células Animais, Instituto Butantan, Av. Vital Brasil, 1500, São Paulo, SP 05503-900, Brazil. 14. DASA Group, Av. Juruá, 434, Barueri, SP 06455-010, Brazil. 15. Ludwig Institute for Cancer Research, Olivia Newton-John Cancer Research Institute, and La Trobe University, Melbourne 3084, Australia.
Abstract
OBJECTIVES: The primary objective was to evaluate the clinical efficacy of hu3S193, a humanized monoclonal antibody against the Lewis-Y antigen, in patients with platinum resistant/refractory ovarian, fallopian tube and primary peritoneal carcinoma. Secondary objectives were safety and pharmacokinetics. In addition, we sought to determine the potential interaction of clinical benefit and patient characteristics. METHODS: This two-stage, multicenter, single arm, phase II trial enrolled eligible patients to receive hu3S193 weekly at a dose of 20mg/m(2) intravenously for 8 weeks (1 cycle) to a maximum of 3 cycles. Efficacy was measured as clinical benefit rate (objective response or stable disease for at least 24 weeks). RESULTS: 26 of 31 patients were eligible for efficacy analysis. No complete/partial responses were observed. Six patients had stable disease for 24+weeks [clinical benefit rate 23% (95% CI=9.77%-46.71%)]. Median PFS was 8.4 weeks (95% CI=6.0 to 16.1). Median PFS differed between patients with no ascites and no visceral disease and patients with ascites and/or visceral disease [16.1 vs. 8.1 weeks (p=0.0058)]. The most commonly reported treatment-related adverse events were fatigue (19.3%) and nausea (16.2%). Allergic reactions occurred in 6 patients (5 with Grade 1/2; 1 with Grade 3). CONCLUSIONS: Hu3S193 lacked sufficient activity in the first stage of the study to open enrollment to the second stage. However, based on the longer PFS in patients with no ascites and no visceral disease, consolidation strategies in platinum sensitive disease are currently being tested.
OBJECTIVES: The primary objective was to evaluate the clinical efficacy of hu3S193, a humanized monoclonal antibody against the Lewis-Y antigen, in patients with platinum resistant/refractory ovarian, fallopian tube and primary peritoneal carcinoma. Secondary objectives were safety and pharmacokinetics. In addition, we sought to determine the potential interaction of clinical benefit and patient characteristics. METHODS: This two-stage, multicenter, single arm, phase II trial enrolled eligible patients to receive hu3S193 weekly at a dose of 20mg/m(2) intravenously for 8 weeks (1 cycle) to a maximum of 3 cycles. Efficacy was measured as clinical benefit rate (objective response or stable disease for at least 24 weeks). RESULTS: 26 of 31 patients were eligible for efficacy analysis. No complete/partial responses were observed. Six patients had stable disease for 24+weeks [clinical benefit rate 23% (95% CI=9.77%-46.71%)]. Median PFS was 8.4 weeks (95% CI=6.0 to 16.1). Median PFS differed between patients with no ascites and no visceral disease and patients with ascites and/or visceral disease [16.1 vs. 8.1 weeks (p=0.0058)]. The most commonly reported treatment-related adverse events were fatigue (19.3%) and nausea (16.2%). Allergic reactions occurred in 6 patients (5 with Grade 1/2; 1 with Grade 3). CONCLUSIONS: Hu3S193 lacked sufficient activity in the first stage of the study to open enrollment to the second stage. However, based on the longer PFS in patients with no ascites and no visceral disease, consolidation strategies in platinum sensitive disease are currently being tested.
Authors: Ingrid J G Burvenich; William Farrugia; Fook T Lee; Bruno Catimel; Zhanqi Liu; Dahna Makris; Diana Cao; Graeme J O'Keefe; Martin W Brechbiel; Dylan King; Violeta Spirkoska; Laura C Allan; Paul A Ramsland; Andrew M Scott Journal: MAbs Date: 2016-03-30 Impact factor: 5.857
Authors: Laura F Hutchins; Issam Makhoul; Peter D Emanuel; Angela Pennisi; Eric R Siegel; Fariba Jousheghany; Xueyan Guo; Anastas D Pashov; Behjatolah Monzavi-Karbassi; Thomas Kieber-Emmons Journal: Oncotarget Date: 2017-10-23
Authors: Laura Testa; Max Mano; Roberto Jun Arai; Renata Colombo Bonadio; Sergio V Serrano; Marina M Costa Zorzetto; Susanne Crocamo; Oren Smaletz; Ruffo Freitas-Junior; Paulo M Hoff Journal: Clinics (Sao Paulo) Date: 2021-10-11 Impact factor: 2.365