PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma

Michael R. Migden, Danny Rischin, Chrysalyne D. Schmults, Alexander Guminski, Axel Hauschild, Karl D. Lewis, Christine H. Chung, Leonel Hernandez-Aya, Annette M. Lim, Anne Lynn S. Chang, Guilherme Rabinowits, Alesha A. Thai, Lara A. Dunn, Brett G.M. Hughes, Nikhil I. Khushalani, Badri Modi, Dirk Schadendorf, Bo Gao, Frank Seebach, Siyu LiJingjin Li, Melissa Mathias, Jocelyn Booth, Kosalai Mohan, Elizabeth Stankevich, Hani M. Babiker, Irene Brana, Marta Gil-Martin, Jade Homsi, Melissa L. Johnson, Victor Moreno, Jiaxin Niu, Taofeek K. Owonikoko, Kyriakos P. Papadopoulos, George D. Yancopoulos, Israel Lowy, Matthew G. Fury

Research output: Contribution to journalArticle

171 Citations (Scopus)

Abstract

BACKGROUND No systemic therapies have been approved for the treatment of advanced cutaneous squamous-cell carcinoma. This cancer may be responsive to immune therapy, because the mutation burden of the tumor is high and the disease risk is strongly associated with immunosuppression. In the dose-escalation portion of the phase 1 study of cemiplimab, a deep and durable response was observed in a patient with metastatic cutaneous squamous-cell carcinoma. METHODS We report the results of the phase 1 study of cemiplimab for expansion cohorts of patients with locally advanced or metastatic cutaneous squamous-cell carcinoma, as well as the results of the pivotal phase 2 study for a cohort of patients with metastatic disease (metastatic-disease cohort). In both studies, the patients received an intravenous dose of cemiplimab (3 mg per kilogram of body weight) every 2 weeks and were assessed for a response every 8 weeks. In the phase 2 study, the primary end point was the response rate, as assessed by independent central review. RESULTS In the expansion cohorts of the phase 1 study, a response to cemiplimab was observed in 13 of 26 patients (50%; 95% confidence interval [CI], 30 to 70). In the metastatic-disease cohort of the phase 2 study, a response was observed in 28 of 59 patients (47%; 95% CI, 34 to 61). The median follow-up was 7.9 months in the metastatic-disease cohort of the phase 2 study. Among the 28 patients who had a response, the duration of response exceeded 6 months in 57%, and 82% continued to have a response and to receive cemiplimab at the time of data cutoff. Adverse events that occurred in at least 15% of the patients in the metastatic-disease cohort of the phase 2 study were diarrhea, fatigue, nausea, constipation, and rash; 7% of the patients discontinued treatment because of an adverse event. CONCLUSIONS Among patients with advanced cutaneous squamous-cell carcinoma, cemiplimab induced a response in approximately half the patients and was associated with adverse events that usually occur with immune checkpoint inhibitors. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov numbers, NCT02383212 and NCT02760498).

Original languageEnglish (US)
Pages (from-to)341-351
Number of pages11
JournalNew England Journal of Medicine
Volume379
Issue number4
DOIs
StatePublished - Jul 26 2018

Fingerprint

Squamous Cell Carcinoma
Skin
Confidence Intervals
Constipation
Therapeutics
Exanthema
Tumor Burden
Immunosuppression
Nausea
Fatigue
Diarrhea
Cohort Studies
Body Weight
Mutation
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Migden, M. R., Rischin, D., Schmults, C. D., Guminski, A., Hauschild, A., Lewis, K. D., ... Fury, M. G. (2018). PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. New England Journal of Medicine, 379(4), 341-351. https://doi.org/10.1056/NEJMoa1805131

PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. / Migden, Michael R.; Rischin, Danny; Schmults, Chrysalyne D.; Guminski, Alexander; Hauschild, Axel; Lewis, Karl D.; Chung, Christine H.; Hernandez-Aya, Leonel; Lim, Annette M.; Chang, Anne Lynn S.; Rabinowits, Guilherme; Thai, Alesha A.; Dunn, Lara A.; Hughes, Brett G.M.; Khushalani, Nikhil I.; Modi, Badri; Schadendorf, Dirk; Gao, Bo; Seebach, Frank; Li, Siyu; Li, Jingjin; Mathias, Melissa; Booth, Jocelyn; Mohan, Kosalai; Stankevich, Elizabeth; Babiker, Hani M.; Brana, Irene; Gil-Martin, Marta; Homsi, Jade; Johnson, Melissa L.; Moreno, Victor; Niu, Jiaxin; Owonikoko, Taofeek K.; Papadopoulos, Kyriakos P.; Yancopoulos, George D.; Lowy, Israel; Fury, Matthew G.

In: New England Journal of Medicine, Vol. 379, No. 4, 26.07.2018, p. 341-351.

Research output: Contribution to journalArticle

Migden, MR, Rischin, D, Schmults, CD, Guminski, A, Hauschild, A, Lewis, KD, Chung, CH, Hernandez-Aya, L, Lim, AM, Chang, ALS, Rabinowits, G, Thai, AA, Dunn, LA, Hughes, BGM, Khushalani, NI, Modi, B, Schadendorf, D, Gao, B, Seebach, F, Li, S, Li, J, Mathias, M, Booth, J, Mohan, K, Stankevich, E, Babiker, HM, Brana, I, Gil-Martin, M, Homsi, J, Johnson, ML, Moreno, V, Niu, J, Owonikoko, TK, Papadopoulos, KP, Yancopoulos, GD, Lowy, I & Fury, MG 2018, 'PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma', New England Journal of Medicine, vol. 379, no. 4, pp. 341-351. https://doi.org/10.1056/NEJMoa1805131
Migden MR, Rischin D, Schmults CD, Guminski A, Hauschild A, Lewis KD et al. PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. New England Journal of Medicine. 2018 Jul 26;379(4):341-351. https://doi.org/10.1056/NEJMoa1805131
Migden, Michael R. ; Rischin, Danny ; Schmults, Chrysalyne D. ; Guminski, Alexander ; Hauschild, Axel ; Lewis, Karl D. ; Chung, Christine H. ; Hernandez-Aya, Leonel ; Lim, Annette M. ; Chang, Anne Lynn S. ; Rabinowits, Guilherme ; Thai, Alesha A. ; Dunn, Lara A. ; Hughes, Brett G.M. ; Khushalani, Nikhil I. ; Modi, Badri ; Schadendorf, Dirk ; Gao, Bo ; Seebach, Frank ; Li, Siyu ; Li, Jingjin ; Mathias, Melissa ; Booth, Jocelyn ; Mohan, Kosalai ; Stankevich, Elizabeth ; Babiker, Hani M. ; Brana, Irene ; Gil-Martin, Marta ; Homsi, Jade ; Johnson, Melissa L. ; Moreno, Victor ; Niu, Jiaxin ; Owonikoko, Taofeek K. ; Papadopoulos, Kyriakos P. ; Yancopoulos, George D. ; Lowy, Israel ; Fury, Matthew G. / PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. In: New England Journal of Medicine. 2018 ; Vol. 379, No. 4. pp. 341-351.
@article{aa08e3d1a9b3441ea158e3a4c32e931f,
title = "PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma",
abstract = "BACKGROUND No systemic therapies have been approved for the treatment of advanced cutaneous squamous-cell carcinoma. This cancer may be responsive to immune therapy, because the mutation burden of the tumor is high and the disease risk is strongly associated with immunosuppression. In the dose-escalation portion of the phase 1 study of cemiplimab, a deep and durable response was observed in a patient with metastatic cutaneous squamous-cell carcinoma. METHODS We report the results of the phase 1 study of cemiplimab for expansion cohorts of patients with locally advanced or metastatic cutaneous squamous-cell carcinoma, as well as the results of the pivotal phase 2 study for a cohort of patients with metastatic disease (metastatic-disease cohort). In both studies, the patients received an intravenous dose of cemiplimab (3 mg per kilogram of body weight) every 2 weeks and were assessed for a response every 8 weeks. In the phase 2 study, the primary end point was the response rate, as assessed by independent central review. RESULTS In the expansion cohorts of the phase 1 study, a response to cemiplimab was observed in 13 of 26 patients (50{\%}; 95{\%} confidence interval [CI], 30 to 70). In the metastatic-disease cohort of the phase 2 study, a response was observed in 28 of 59 patients (47{\%}; 95{\%} CI, 34 to 61). The median follow-up was 7.9 months in the metastatic-disease cohort of the phase 2 study. Among the 28 patients who had a response, the duration of response exceeded 6 months in 57{\%}, and 82{\%} continued to have a response and to receive cemiplimab at the time of data cutoff. Adverse events that occurred in at least 15{\%} of the patients in the metastatic-disease cohort of the phase 2 study were diarrhea, fatigue, nausea, constipation, and rash; 7{\%} of the patients discontinued treatment because of an adverse event. CONCLUSIONS Among patients with advanced cutaneous squamous-cell carcinoma, cemiplimab induced a response in approximately half the patients and was associated with adverse events that usually occur with immune checkpoint inhibitors. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov numbers, NCT02383212 and NCT02760498).",
author = "Migden, {Michael R.} and Danny Rischin and Schmults, {Chrysalyne D.} and Alexander Guminski and Axel Hauschild and Lewis, {Karl D.} and Chung, {Christine H.} and Leonel Hernandez-Aya and Lim, {Annette M.} and Chang, {Anne Lynn S.} and Guilherme Rabinowits and Thai, {Alesha A.} and Dunn, {Lara A.} and Hughes, {Brett G.M.} and Khushalani, {Nikhil I.} and Badri Modi and Dirk Schadendorf and Bo Gao and Frank Seebach and Siyu Li and Jingjin Li and Melissa Mathias and Jocelyn Booth and Kosalai Mohan and Elizabeth Stankevich and Babiker, {Hani M.} and Irene Brana and Marta Gil-Martin and Jade Homsi and Johnson, {Melissa L.} and Victor Moreno and Jiaxin Niu and Owonikoko, {Taofeek K.} and Papadopoulos, {Kyriakos P.} and Yancopoulos, {George D.} and Israel Lowy and Fury, {Matthew G.}",
year = "2018",
month = "7",
day = "26",
doi = "10.1056/NEJMoa1805131",
language = "English (US)",
volume = "379",
pages = "341--351",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "4",

}

TY - JOUR

T1 - PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma

AU - Migden, Michael R.

AU - Rischin, Danny

AU - Schmults, Chrysalyne D.

AU - Guminski, Alexander

AU - Hauschild, Axel

AU - Lewis, Karl D.

AU - Chung, Christine H.

AU - Hernandez-Aya, Leonel

AU - Lim, Annette M.

AU - Chang, Anne Lynn S.

AU - Rabinowits, Guilherme

AU - Thai, Alesha A.

AU - Dunn, Lara A.

AU - Hughes, Brett G.M.

AU - Khushalani, Nikhil I.

AU - Modi, Badri

AU - Schadendorf, Dirk

AU - Gao, Bo

AU - Seebach, Frank

AU - Li, Siyu

AU - Li, Jingjin

AU - Mathias, Melissa

AU - Booth, Jocelyn

AU - Mohan, Kosalai

AU - Stankevich, Elizabeth

AU - Babiker, Hani M.

AU - Brana, Irene

AU - Gil-Martin, Marta

AU - Homsi, Jade

AU - Johnson, Melissa L.

AU - Moreno, Victor

AU - Niu, Jiaxin

AU - Owonikoko, Taofeek K.

AU - Papadopoulos, Kyriakos P.

AU - Yancopoulos, George D.

AU - Lowy, Israel

AU - Fury, Matthew G.

PY - 2018/7/26

Y1 - 2018/7/26

N2 - BACKGROUND No systemic therapies have been approved for the treatment of advanced cutaneous squamous-cell carcinoma. This cancer may be responsive to immune therapy, because the mutation burden of the tumor is high and the disease risk is strongly associated with immunosuppression. In the dose-escalation portion of the phase 1 study of cemiplimab, a deep and durable response was observed in a patient with metastatic cutaneous squamous-cell carcinoma. METHODS We report the results of the phase 1 study of cemiplimab for expansion cohorts of patients with locally advanced or metastatic cutaneous squamous-cell carcinoma, as well as the results of the pivotal phase 2 study for a cohort of patients with metastatic disease (metastatic-disease cohort). In both studies, the patients received an intravenous dose of cemiplimab (3 mg per kilogram of body weight) every 2 weeks and were assessed for a response every 8 weeks. In the phase 2 study, the primary end point was the response rate, as assessed by independent central review. RESULTS In the expansion cohorts of the phase 1 study, a response to cemiplimab was observed in 13 of 26 patients (50%; 95% confidence interval [CI], 30 to 70). In the metastatic-disease cohort of the phase 2 study, a response was observed in 28 of 59 patients (47%; 95% CI, 34 to 61). The median follow-up was 7.9 months in the metastatic-disease cohort of the phase 2 study. Among the 28 patients who had a response, the duration of response exceeded 6 months in 57%, and 82% continued to have a response and to receive cemiplimab at the time of data cutoff. Adverse events that occurred in at least 15% of the patients in the metastatic-disease cohort of the phase 2 study were diarrhea, fatigue, nausea, constipation, and rash; 7% of the patients discontinued treatment because of an adverse event. CONCLUSIONS Among patients with advanced cutaneous squamous-cell carcinoma, cemiplimab induced a response in approximately half the patients and was associated with adverse events that usually occur with immune checkpoint inhibitors. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov numbers, NCT02383212 and NCT02760498).

AB - BACKGROUND No systemic therapies have been approved for the treatment of advanced cutaneous squamous-cell carcinoma. This cancer may be responsive to immune therapy, because the mutation burden of the tumor is high and the disease risk is strongly associated with immunosuppression. In the dose-escalation portion of the phase 1 study of cemiplimab, a deep and durable response was observed in a patient with metastatic cutaneous squamous-cell carcinoma. METHODS We report the results of the phase 1 study of cemiplimab for expansion cohorts of patients with locally advanced or metastatic cutaneous squamous-cell carcinoma, as well as the results of the pivotal phase 2 study for a cohort of patients with metastatic disease (metastatic-disease cohort). In both studies, the patients received an intravenous dose of cemiplimab (3 mg per kilogram of body weight) every 2 weeks and were assessed for a response every 8 weeks. In the phase 2 study, the primary end point was the response rate, as assessed by independent central review. RESULTS In the expansion cohorts of the phase 1 study, a response to cemiplimab was observed in 13 of 26 patients (50%; 95% confidence interval [CI], 30 to 70). In the metastatic-disease cohort of the phase 2 study, a response was observed in 28 of 59 patients (47%; 95% CI, 34 to 61). The median follow-up was 7.9 months in the metastatic-disease cohort of the phase 2 study. Among the 28 patients who had a response, the duration of response exceeded 6 months in 57%, and 82% continued to have a response and to receive cemiplimab at the time of data cutoff. Adverse events that occurred in at least 15% of the patients in the metastatic-disease cohort of the phase 2 study were diarrhea, fatigue, nausea, constipation, and rash; 7% of the patients discontinued treatment because of an adverse event. CONCLUSIONS Among patients with advanced cutaneous squamous-cell carcinoma, cemiplimab induced a response in approximately half the patients and was associated with adverse events that usually occur with immune checkpoint inhibitors. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov numbers, NCT02383212 and NCT02760498).

UR - http://www.scopus.com/inward/record.url?scp=85050575310&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85050575310&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa1805131

DO - 10.1056/NEJMoa1805131

M3 - Article

C2 - 29863979

AN - SCOPUS:85050575310

VL - 379

SP - 341

EP - 351

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 4

ER -