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Nivolumab plusIpilimumab inAdvanced Melanoma Jedd D. WolchokHarriet M. KlugerMargaret K. Callahan2013 год

Nivolumab plus Ipilimumab in Advanced Melanoma
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Аннотация: In patients with melanoma, ipilimumab (an antibody against cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4]) prolongs overall survival, and nivolumab (an antibody against the programmed death 1 [PD-1] receptor) produced durable tumor regression in a phase 1 trial. On the basis of their distinct immunologic mechanisms of action and supportive preclinical data, we conducted a phase 1 trial of nivolumab combined with ipilimumab in patients with advanced melanoma.We administered intravenous doses of nivolumab and ipilimumab in patients every 3 weeks for 4 doses, followed by nivolumab alone every 3 weeks for 4 doses (concurrent regimen). The combined treatment was subsequently administered every 12 weeks for up to 8 doses. In a sequenced regimen, patients previously treated with ipilimumab received nivolumab every 2 weeks for up to 48 doses.A total of 53 patients received concurrent therapy with nivolumab and ipilimumab, and 33 received sequenced treatment. The objective-response rate (according to modified World Health Organization criteria) for all patients in the concurrent-regimen group was 40%. Evidence of clinical activity (conventional, unconfirmed, or immune-related response or stable disease for ≥24 weeks) was observed in 65% of patients. At the maximum doses that were associated with an acceptable level of adverse events (nivolumab at a dose of 1 mg per kilogram of body weight and ipilimumab at a dose of 3 mg per kilogram), 53% of patients had an objective response, all with tumor reduction of 80% or more. Grade 3 or 4 adverse events related to therapy occurred in 53% of patients in the concurrent-regimen group but were qualitatively similar to previous experience with monotherapy and were generally reversible. Among patients in the sequenced-regimen group, 18% had grade 3 or 4 adverse events related to therapy and the objective-response rate was 20%.Concurrent therapy with nivolumab and ipilimumab had a manageable safety profile and provided clinical activity that appears to be distinct from that in published data on monotherapy, with rapid and deep tumor regression in a substantial proportion of patients. (Funded by Bristol-Myers Squibb and Ono Pharmaceutical; ClinicalTrials.gov number, NCT01024231.).
Год издания: 2013
Авторы: Jedd D. Wolchok, Harriet M. Kluger, Margaret K. Callahan, Michael A. Postow, Naiyer A. Rizvi, Alexander M. Lesokhin, Neil H. Segal, Charlotte E. Ariyan, RuthAnn Gordon, Kathleen Reed, Matthew M. Burke, Anne Caldwell, Stephanie Anne Kronenberg, Blessing Agunwamba, Xiaoling Zhang, Israel Lowy, H. David Inzunza, William F. Feely, Christine E. Horak, Quan Hong, Alan J. Korman, Jon M. Wigginton, Ashok Gupta, Mario Sznol
Издательство: Massachusetts Medical Society
Источник: New England Journal of Medicine
Ключевые слова: Cancer Immunotherapy and Biomarkers, CAR-T cell therapy research, Immunotherapy and Immune Responses
Другие ссылки: New England Journal of Medicine (PDF)
New England Journal of Medicine (HTML)
Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
PubMed Central (HTML)
PubMed (HTML)