PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma

M. R. Migden, D. Rischin, C. D. Schmults, A. Guminski, A. Hauschild, K. D. Lewis, C. H. Chung, L. Hernandez-Aya, A. M. Lim, A. L. S. Chang, G. Rabinowits, A. A. Thai, L. A. Dunn, B. G. M. Hughes, N. I. Khushalani, B. Modi, D. Schadendorf, B. Gao, F. Seebach, S. Li & 17 others J. Li, M. Mathias, J. Booth, K. Mohan, E. Stankevich, H. M. Babiker, I. Brana, M. Gil-Martin, J. Homsi, M. L. Johnson, V. Moreno, J. Niu, T. K. Owonikoko, K. P. Papadopoulos, G. D. Yancopoulos, I. Lowy, M. G. Fury

Research output: Contribution to journalArticle

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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.

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

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
Migden, M. R. ; Rischin, D. ; Schmults, C. D. ; Guminski, A. ; Hauschild, A. ; Lewis, K. D. ; Chung, C. H. ; Hernandez-Aya, L. ; Lim, A. M. ; Chang, A. L. S. ; Rabinowits, G. ; Thai, A. A. ; Dunn, L. A. ; Hughes, B. G. M. ; Khushalani, N. I. ; Modi, B. ; Schadendorf, D. ; Gao, B. ; Seebach, F. ; Li, S. ; Li, J. ; Mathias, M. ; Booth, J. ; Mohan, K. ; Stankevich, E. ; Babiker, H. M. ; Brana, I. ; Gil-Martin, M. ; Homsi, J. ; Johnson, M. L. ; Moreno, V. ; Niu, J. ; Owonikoko, T. K. ; Papadopoulos, K. P. ; Yancopoulos, G. D. ; Lowy, I. ; Fury, M. 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.
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abstract = "BACKGROUNDNo 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.METHODSWe 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.RESULTSIn 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.CONCLUSIONSAmong 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.",
keywords = "NONMELANOMA SKIN-CANCER, MISMATCH-REPAIR DEFICIENCY, TUMOR MUTATIONAL BURDEN, SOLID TUMORS, LANDSCAPE, SENSITIVITY, MANAGEMENT, GUIDELINE, CONSENSUS",
author = "Migden, {M. R.} and D. Rischin and Schmults, {C. D.} and A. Guminski and A. Hauschild and Lewis, {K. D.} and Chung, {C. H.} and L. Hernandez-Aya and Lim, {A. M.} and Chang, {A. L. S.} and G. Rabinowits and Thai, {A. A.} and Dunn, {L. A.} and Hughes, {B. G. M.} and Khushalani, {N. I.} and B. Modi and D. Schadendorf and B. Gao and F. Seebach and S. Li and J. Li and M. Mathias and J. Booth and K. Mohan and E. Stankevich and Babiker, {H. M.} and I. Brana and M. Gil-Martin and J. Homsi and Johnson, {M. L.} and V. Moreno and J. Niu and Owonikoko, {T. K.} and Papadopoulos, {K. P.} and Yancopoulos, {G. D.} and I. Lowy and Fury, {M. G.}",
year = "2018",
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language = "English",
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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

PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma. / Migden, M. R.; Rischin, D.; Schmults, C. D.; Guminski, A.; Hauschild, A.; Lewis, K. D.; Chung, C. H.; Hernandez-Aya, L.; Lim, A. M.; Chang, A. L. S.; Rabinowits, G.; Thai, A. A.; Dunn, L. A.; Hughes, B. G. M.; Khushalani, N. I.; Modi, B.; Schadendorf, D.; Gao, B.; Seebach, F.; Li, S.; Li, J.; Mathias, M.; Booth, J.; Mohan, K.; Stankevich, E.; Babiker, H. M.; Brana, I.; Gil-Martin, M.; Homsi, J.; Johnson, M. L.; Moreno, V.; Niu, J.; Owonikoko, T. K.; Papadopoulos, K. P.; Yancopoulos, G. D.; Lowy, I.; Fury, M. G.

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

Research output: Contribution to journalArticle

TY - JOUR

T1 - PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma

AU - Migden, M. R.

AU - Rischin, D.

AU - Schmults, C. D.

AU - Guminski, A.

AU - Hauschild, A.

AU - Lewis, K. D.

AU - Chung, C. H.

AU - Hernandez-Aya, L.

AU - Lim, A. M.

AU - Chang, A. L. S.

AU - Rabinowits, G.

AU - Thai, A. A.

AU - Dunn, L. A.

AU - Hughes, B. G. M.

AU - Khushalani, N. I.

AU - Modi, B.

AU - Schadendorf, D.

AU - Gao, B.

AU - Seebach, F.

AU - Li, S.

AU - Li, J.

AU - Mathias, M.

AU - Booth, J.

AU - Mohan, K.

AU - Stankevich, E.

AU - Babiker, H. M.

AU - Brana, I.

AU - Gil-Martin, M.

AU - Homsi, J.

AU - Johnson, M. L.

AU - Moreno, V.

AU - Niu, J.

AU - Owonikoko, T. K.

AU - Papadopoulos, K. P.

AU - Yancopoulos, G. D.

AU - Lowy, I.

AU - Fury, M. G.

PY - 2018/7/26

Y1 - 2018/7/26

N2 - BACKGROUNDNo 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.METHODSWe 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.RESULTSIn 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.CONCLUSIONSAmong 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.

AB - BACKGROUNDNo 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.METHODSWe 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.RESULTSIn 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.CONCLUSIONSAmong 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.

KW - NONMELANOMA SKIN-CANCER

KW - MISMATCH-REPAIR DEFICIENCY

KW - TUMOR MUTATIONAL BURDEN

KW - SOLID TUMORS

KW - LANDSCAPE

KW - SENSITIVITY

KW - MANAGEMENT

KW - GUIDELINE

KW - CONSENSUS

U2 - 10.1056/NEJMoa1805131

DO - 10.1056/NEJMoa1805131

M3 - Article

VL - 379

SP - 341

EP - 351

JO - The New England Journal of Medicine

JF - The New England Journal of Medicine

SN - 0028-4793

IS - 4

ER -

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