Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma

Omid Hamid, Caroline Robert, Adil Daud, F. Stephen Hodi, Wen Jen Hwu, Richard Kefford, Jedd D. Wolchok, Peter Hersey, Richard W. Joseph, Jeffrey S. Weber, Roxana Dronca, Tara C. Gangadhar, Amita Patnaik, Hassane Zarour, Anthony M. Joshua, Kevin Gergich, Jeroen Elassaiss-Schaap, Alain Algazi, Christine Mateus, Peter BoasbergPaul C. Tumeh, Bartosz Chmielowski, Scot W. Ebbinghaus, Xiaoyun Nicole Li, S. Peter Kang, Antoni Ribas

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2247 Scopus citations

Abstract

BACKGROUND: The programmed death 1 (PD-1) receptor is a negative regulator of T-cell effector mechanisms that limits immune responses against cancer. We tested the anti-PD-1 antibody lambrolizumab (previously known as MK-3475) in patients with advanced melanoma. METHODS: We administered lambrolizumab intravenously at a dose of 10 mg per kilogram of body weight every 2 or 3 weeks or 2 mg per kilogram every 3 weeks in patients with advanced melanoma, both those who had received prior treatment with the immune checkpoint inhibitor ipilimumab and those who had not. Tumor responses were assessed every 12 weeks. RESULTS: A total of 135 patients with advanced melanoma were treated. Common adverse events attributed to treatment were fatigue, rash, pruritus, and diarrhea; most of the adverse events were low grade. The confirmed response rate across all dose cohorts, evaluated by central radiologic review according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, was 38% (95% confidence interval [CI], 25 to 44), with the highest confirmed response rate observed in the cohort that received 10 mg per kilogram every 2 weeks (52%; 95% CI, 38 to 66). The response rate did not differ significantly between patients who had received prior ipilimumab treatment and those who had not (confirmed response rate, 38% [95% CI, 23 to 55] and 37% [95% CI, 26 to 49], respectively). Responses were durable in the majority of patients (median follow-up, 11 months among patients who had a response); 81% of the patients who had a response (42 of 52) were still receiving treatment at the time of analysis in March 2013. The overall median progression-free survival among the 135 patients was longer than 7 months. CONCLUSIONS: In patients with advanced melanoma, including those who had had disease progression while they had been receiving ipilimumab, treatment with lambrolizumab resulted in a high rate of sustained tumor regression, with mainly grade 1 or 2 toxic effects.

Original languageEnglish (US)
Pages (from-to)134-144
Number of pages11
JournalNew England Journal of Medicine
Volume369
Issue number2
DOIs
StatePublished - 2013

ASJC Scopus subject areas

  • Medicine(all)

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    Hamid, O., Robert, C., Daud, A., Hodi, F. S., Hwu, W. J., Kefford, R., Wolchok, J. D., Hersey, P., Joseph, R. W., Weber, J. S., Dronca, R., Gangadhar, T. C., Patnaik, A., Zarour, H., Joshua, A. M., Gergich, K., Elassaiss-Schaap, J., Algazi, A., Mateus, C., ... Ribas, A. (2013). Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. New England Journal of Medicine, 369(2), 134-144. https://doi.org/10.1056/NEJMoa1305133