| Autor: |
Lada Mitchell, J. Pigozzo, K. Bennett, C.S.P. Lima, Silvia Park, Juan F. Medina, Antonio M. Grimaldi, David F. McDermott, Chi Hoon Maeng, R. Tanaka, L. Ridolfi, C.J.A. Punt, O.V. Korotkova, Amelia Lissia, D.M. Chen, W. Chang, J. De Vries, L. Pericleous, Ugo Marone, Corrado Caracò, Winald R. Gerritsen, E. Midena, C. Lebbé, Christian U. Blank, C. Brocia, E.F.D. Costa, R. Bassett, A. Sekulic, Tania Labiano, E. Fonsatti, D. Lawrence, Paola Queirolo, J.D. Wolchok, Stefano Mori, R. Dummer, C. Aliberti, Ruth Plummer, S. Francis, N. Vanhoutte, R. Wintherhalder, G.A.S. Nogueira, A. Amin, Jonathan D. Schwartz, M. Guida, C. Turtschi, Gerty Schreibelt, P. Mut, A. Ballesteros, S-H Lee, Anna C. Pavlick, Ester Simeone, M. Sini, K. Namikawa, R. Marconcini, Shibao Feng, Nicola Mozzillo, L. Veronese, C. Gamez, Merrick I. Ross, Donna Rowen, R. Labianca, T. Kirchhoff, M. Altomonte, Michele Maio, A. Batty, S. Yoo, James Larkin, Lev V. Demidov, Alessandro Testori, Omid Hamid, Sarvendra Kumar, Michael P. Brown, Jochen Utikal, J.A. Lopez Martin, R. Shapiro, Maria D. Lozano, N. Fischer, S. Ariad, B. Shafaeddin-Schreve, V. Chairion Sileni, M.K. Choi, Jung Yong Hong, Shreyaskumar Patel, Dimitris Bafaloukos, H. Yue, José I. Echeveste, M. Novy, M. Lebmeier, David R. Minor, F. Zambrana, M. Colombino, B. Campos, E. Muñoz, Simone M. Goldinger, D. Cumplido, P.L. Pilati, D. Lee, Giusy Gentilcore, G. Lucisano, J. Richards, Mario Sznol, F.S. Hodi, B. Merelli, Jeffrey S. Weber, M. Traversa, C. Oberkanins, Stephen M Murray, Suzanne L. Topalian, Vincent Brichard, I. Lazarev, D. Piazzalunga, F. De Galitiis, E. Wachter, C. Rubino, D. Opatt McDowell, Virginia Ferraresi, I.V. Samoylenko, M. Sereno, John A. Thompson, G. Colucci, P. Petrillo, M. Montañana, G. Di Monta, M. Maur, E. Bajetta, C. Oliveira, Kevin M. Chin, Sarah Danson, Anthony E. Oro, Igor Bondarenko, J.A. Rinck-Junior, W.J. Lesterhuis, E. Bertocci, A. Garcia Castano, T.N. Zabotina, S. Pisconti, S. Ellis, M. Hidalgo, A. Berrocal, Jeffrey A. Sosman, Sara Valpione, Miguel F. Sanmamed, Pier Francesco Ferrucci, Y. Sasajima, J. Perez, H. Linardou, F. De Rosa, J. Thompson, S. Stragliotto, Patrick Hwu, B.J. Coventry, M. Gillet, A.M. Di Giacomo, P.R. Hilfiker, L. Marchesi, Iman Osman, J. Rendleman, C. Nuzzo, G. Imberti, Edward McKenna, L. Di Guardo, Paul Nathan, I.N. Mikhaylova, Jenny Nobes, Antonio Cossu, Miguel Angel Idoate, Mario Mandalà, Giuseppe Palmieri, M. Ochoa de Olza, T. Nikoglou, M. Del Vecchio, B. Salaun, A. Cramarossa, J.M. Caminal, M. Biagioli, H. Tsuda, M.M. van Rossum, K. Harmankaya, J. Cortes, A.M. Moraes, H. Shaw, R. Danielli, S. Mosconi, John D. Hainsworth, Agop Y. Bedikian, G. Kriegshäuser, C.R. Scoggins, J. Valdivia, L. Pilla, R. Ridolfi, L.G. Campana, Christoph Rochlitz, M. Ma, V. Escrig, M.L. Cintra, I. Pesce, L. Calabrò, Karl D. Lewis, Russell S. Berman, Erik H.J.G. Aarntzen, Bart Neyns, T. Puertolas, J.A. Solomon, E. Castanon Alvarez, Georgia Kollia, F. Siannis, Katrin Conen, G.Z. Chkadua, Ana Arance, J.W. Lee, Caroline Robert, G.J. Lourenço, Jedd D. Wolchok, Lucia Benedetto, B.M. Smithers, N. Yamazaki, Axel Hauschild, A. Gupta, A. Gianatti, Luc Thomas, G. Rinaldi, A. Albano, D.P. Lawrence, F. Cognetti, A. Balogh, B. Rauscher, J.M. Wigginton, Carlo Tondini, W. Hwu, K. Baryshnikov, Y.S. Kim, A. Yakobson, J.M. Piulats, Ralf Gutzmer, Claus Garbe, R. Parrozzani, Kalijn F. Bol, M. Aglietta, V. Chiarion Sileni, Paolo A. Ascierto, M.R. Migden, P. Rojas, Nicholas E. Papadopoulos, V. De Giorgi, S. Martin Algarra, A. Tsutsumida, Ernie Marshall, S. Shang, S.V.L. Nicoletti, Joannes F M Jacobs, Anne Lynn S. Chang, J. Mayordomo, L. Cykowski, Sung Heon Kim, M. Gonzalez Cao, Sanjiv S. Agarwala, Michael S. Gordon, Carl G. Figdor, L. Alonso, Richard D. Carvajal, M.G. Bernengo, K. B. Kim, Daniela Massi, L. Dirix, O. Michielin, Nerea Gomez, Pippa Corrie, E. Ortega, Diana Giannarelli, E. Levchenko, H.R. Alexander, Alfonso Gurpide, P.M. LoRusso, Günther F.L. Hofbauer, J.D. Rinderknecht, B. Winn, L. Rivoltini, J. Hou, M. Aieta, S. Rossi, M.B. McHenry, Alejo Rodriguez-Vida, N. Eggmann, Alfred Zippelius, Y. Shao, G.J. Weiss, Fabrizio Ayala |
| Rok vydání: |
2012 |
| Předmět: |
|
| Zdroj: |
Annals of Oncology. 23:ix361 |
| ISSN: |
0923-7534 |
| Popis: |
Purpose BMS-936558 is a monoclonal antibody that blocks the PD-1 co-inhibitory receptor expressed by activated T cells. This study describes its activity and safety in pts with previously treated advanced MEL. Methods BMS-936558 was administered IV q2wk to pts with various tumors at 0.1 - 10 mg/kg during dose-escalation and/or cohort expansion. Pts received up to 12 cycles (4 doses/cycle) of treatment or until unacceptable toxicity, confirmed progressive disease, or complete response. Clinical activity was assessed by RECIST v1.0. Results As of Feb 24, 2012, 104 MEL pts had received BMS-936558 at 0.1 (n = 17), 0.3 (n = 19), 1 (n = 31), 3 (n = 17), or 10 mg/kg (n = 20). ECOG performance status was 0/1/2 in 63/38/3 pts, respectively. Most pts (67/104) had received prior immunotherapy (IT); prior anti-CTLA-4, -PD-1, or -PD-L1 was not permitted. The number of prior therapies was 1 (39%), 2 (35%), or ≥3 (26%). Median therapy duration was 20 wks (range 2.0 - 121.7 wks). The incidence of grade 3 - 4 related AEs was 20% and included gastrointestinal (4%), endocrine (2%), and hepatobiliary disorders (1%). There were no drug-related deaths in MEL pts. Clinical activity (responses or prolonged stable disease) was observed at all doses (Table). Of the 26/94 (28%) evaluable responders, 19 (73%) are ongoing ranging from 1.9+ to 24.9+ months. For the 23 responders followed ≥6 months from first dose on study, 16 (70%) are progression free. ORs occurred in pts with visceral or bone metastases. Six pts (6%; 95% CI 2 - 13%) had prolonged SD (≥24 wk); 3 pts had a persistent decrease in target lesion tumor burden in the presence of new lesions and were not categorized as responders. Conclusions BMS-936558 had durable clinical benefit in pts with advanced MEL, including those who had received prior IT. Additional long-term follow-up data will be reported. Dose, (mg/kg) No. ptsa ORR, No. pts (%) [95% CI] PFSR at 24 wk (%) [95% CI] 0.1 14 4 (29) [8 - 58] 40 [13 - 66] 0.3 16 3 (19) [4 - 46] 31 [9 - 54] 1 27 8 (30) [14 - 50] 45 [26 - 65] 3 17 7 (41) [18 - 67] * 55 [30 - 80] 10 20 4 (20) [6 - 44] 30 [9 - 51] * 1 CR aResponse-evaluable pts dosed by 7/01/2011 ORR = objective response rate ([{CR + PR} ÷ n] × 100); PFSR = progression-free survival rate. Disclosure J. Sosman: Research Funding: Bristol-Myers Squibb (myself). M. Sznol: Consultant or Advisory Role: Bristol-Myers Squibb (myself, compensated). Research Funding: Bristol-Myers Squibb (myself, clinical trials funding). D.F. McDermott: Advisory Board Role: Bristol-Myers Squibb (myself). R. Carvajal: Research Funding: Bristol-Myers Squibb (myself). S.L. Topalian: Consultant or Advisory Role: Bristol-Myers Squibb (myself, immediate family member, uncompensated). Research Funding: Bristol-Myers Squibb (myself). J.M. Wigginton: Employment or Leadership Position: Bristol-Myers Squibb (myself, employment, compensated). Stock Ownership: Bristol-Myers Squibb (myself). G. Kollia: Employment or Leadership Role: Bristol-Myers Squibb (employment, myself, compensated). Stock Ownership: Bristol-Myers Squibb/BMY stocks (myself). A. Gupta: Employment or Leadership Role: Bristol-Myers Squibb (employment, myself, compensated). Stock Ownership: Bristol-Myers Squibb (myself). F.S. Hodi: Consultant or Advisory Role: Bristol-Myers Squibb (myself, uncompensated). Research Funding: Bristol-Myers Squibb (myself). All other authors have declared no conflicts of interest. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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