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 S 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

Research output: Contribution to journalArticle

2144 Citations (Scopus)

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

Fingerprint

Melanoma
Safety
Neoplasms
Confidence Intervals
Therapeutics
pembrolizumab
Death Domain Receptors
Poisons
Pruritus
Exanthema
Disease-Free Survival
Fatigue
Disease Progression
Diarrhea
Body Weight
T-Lymphocytes
Antibodies
ipilimumab

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Hamid, O., Robert, C., Daud, A., Hodi, F. S., Hwu, W. J., Kefford, R., ... 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

Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. / Hamid, Omid; Robert, Caroline; Daud, Adil; Hodi, F. Stephen; Hwu, Wen Jen; Kefford, Richard; Wolchok, Jedd D.; Hersey, Peter; Joseph, Richard W; Weber, Jeffrey S.; Dronca, Roxana S; Gangadhar, Tara C.; Patnaik, Amita; Zarour, Hassane; Joshua, Anthony M.; Gergich, Kevin; Elassaiss-Schaap, Jeroen; Algazi, Alain; Mateus, Christine; Boasberg, Peter; Tumeh, Paul C.; Chmielowski, Bartosz; Ebbinghaus, Scot W.; Li, Xiaoyun Nicole; Kang, S. Peter; Ribas, Antoni.

In: New England Journal of Medicine, Vol. 369, No. 2, 2013, p. 134-144.

Research output: Contribution to journalArticle

Hamid, O, Robert, C, Daud, A, Hodi, FS, Hwu, WJ, Kefford, R, Wolchok, JD, Hersey, P, Joseph, RW, Weber, JS, Dronca, RS, Gangadhar, TC, Patnaik, A, Zarour, H, Joshua, AM, Gergich, K, Elassaiss-Schaap, J, Algazi, A, Mateus, C, Boasberg, P, Tumeh, PC, Chmielowski, B, Ebbinghaus, SW, Li, XN, Kang, SP & Ribas, A 2013, 'Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma', New England Journal of Medicine, vol. 369, no. 2, pp. 134-144. https://doi.org/10.1056/NEJMoa1305133
Hamid, Omid ; Robert, Caroline ; Daud, Adil ; Hodi, F. Stephen ; Hwu, Wen Jen ; Kefford, Richard ; Wolchok, Jedd D. ; Hersey, Peter ; Joseph, Richard W ; Weber, Jeffrey S. ; Dronca, Roxana S ; Gangadhar, Tara C. ; Patnaik, Amita ; Zarour, Hassane ; Joshua, Anthony M. ; Gergich, Kevin ; Elassaiss-Schaap, Jeroen ; Algazi, Alain ; Mateus, Christine ; Boasberg, Peter ; Tumeh, Paul C. ; Chmielowski, Bartosz ; Ebbinghaus, Scot W. ; Li, Xiaoyun Nicole ; Kang, S. Peter ; Ribas, Antoni. / Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. In: New England Journal of Medicine. 2013 ; Vol. 369, No. 2. pp. 134-144.
@article{fd936be08dcd4431a8fdcee5764ffe1b,
title = "Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma",
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.",
author = "Omid Hamid and Caroline Robert and Adil Daud and Hodi, {F. Stephen} and Hwu, {Wen Jen} and Richard Kefford and Wolchok, {Jedd D.} and Peter Hersey and Joseph, {Richard W} and Weber, {Jeffrey S.} and Dronca, {Roxana S} and Gangadhar, {Tara C.} and Amita Patnaik and Hassane Zarour and Joshua, {Anthony M.} and Kevin Gergich and Jeroen Elassaiss-Schaap and Alain Algazi and Christine Mateus and Peter Boasberg and Tumeh, {Paul C.} and Bartosz Chmielowski and Ebbinghaus, {Scot W.} and Li, {Xiaoyun Nicole} and Kang, {S. Peter} and Antoni Ribas",
year = "2013",
doi = "10.1056/NEJMoa1305133",
language = "English (US)",
volume = "369",
pages = "134--144",
journal = "New England Journal of Medicine",
issn = "1533-4406",
publisher = "Massachussetts Medical Society",
number = "2",

}

TY - JOUR

T1 - Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma

AU - Hamid, Omid

AU - Robert, Caroline

AU - Daud, Adil

AU - Hodi, F. Stephen

AU - Hwu, Wen Jen

AU - Kefford, Richard

AU - Wolchok, Jedd D.

AU - Hersey, Peter

AU - Joseph, Richard W

AU - Weber, Jeffrey S.

AU - Dronca, Roxana S

AU - Gangadhar, Tara C.

AU - Patnaik, Amita

AU - Zarour, Hassane

AU - Joshua, Anthony M.

AU - Gergich, Kevin

AU - Elassaiss-Schaap, Jeroen

AU - Algazi, Alain

AU - Mateus, Christine

AU - Boasberg, Peter

AU - Tumeh, Paul C.

AU - Chmielowski, Bartosz

AU - Ebbinghaus, Scot W.

AU - Li, Xiaoyun Nicole

AU - Kang, S. Peter

AU - Ribas, Antoni

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84879759020&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84879759020&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa1305133

DO - 10.1056/NEJMoa1305133

M3 - Article

C2 - 23724846

AN - SCOPUS:84879759020

VL - 369

SP - 134

EP - 144

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 1533-4406

IS - 2

ER -