Evaluation of Two Dosing Regimens for Nivolumab in Combination With Ipilimumab in Patients With Advanced Melanoma

Results From the Phase IIIb/IV CheckMate 511 Trial

Celeste Lebbé, Nicolas Meyer, Laurent Mortier, Ivan Marquez-Rodas, Caroline Robert, Piotr Rutkowski, Alexander M Menzies, Thomas Eigentler, Paolo A Ascierto, Michael Smylie, Dirk Schadendorf, Mazhar Ajaz, Inge Marie Svane, Rene Gonzalez, Linda Rollin, Jennifer Lord-Bessen, Abdel Saci, Elena Grigoryeva, Jacopo Pigozzo

Research output: Contribution to journalArticle

Abstract

PURPOSE: Nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (NIVO1+IPI3) is approved for first-line treatment of patients with advanced melanoma in several countries. We conducted a phase IIIb/IV study (CheckMate 511) to determine if nivolumab 3 mg/kg plus ipilimumab 1 mg/kg (NIVO3+IPI1) improves the safety profile of the combination.

PATIENTS AND METHODS: Patients (N = 360) age 18 years or older with previously untreated, unresectable stage III or IV melanoma were randomly assigned 1:1 to NIVO3+IPI1 or NIVO1+IPI3 once every 3 weeks for four doses. After 6 weeks, all patients received NIVO 480 mg once every 4 weeks until disease progression or unacceptable toxicity. The primary end point was a comparison of the incidence of treatment-related grade 3 to 5 adverse events (AEs) between groups. Secondary end points included descriptive analyses of objective response rate, progression-free survival, and overall survival. The study was not designed to formally demonstrate noninferiority of NIVO3+IPI1 to NIVO1+IPI3 for efficacy end points.

RESULTS: At a minimum follow-up of 12 months, incidence of treatment-related grade 3 to 5 AEs was 34% with NIVO3+IPI1 versus 48% with NIVO1+IPI3 ( P = .006). In descriptive analyses, objective response rate was 45.6% in the NIVO3+IPI1 group and 50.6% in the NIVO1+IPI3 group, with complete responses in 15.0% and 13.5% of patients, respectively. Median progression-free survival was 9.9 months in the NIVO3+IPI1 group and 8.9 months in the NIVO1+IPI3 group. Median overall survival was not reached in either group.

CONCLUSION: The CheckMate 511 study met its primary end point, demonstrating a significantly lower incidence of treatment-related grade 3-5 AEs with NIVO3+IPI1 versus NIVO1+IPI3. Descriptive analyses showed that there were no meaningful differences between the groups for any efficacy end point, although longer follow up may help to better characterize efficacy outcomes.

Original languageEnglish
Pages (from-to)867-875
Number of pages9
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology
Volume37
Issue number11
DOIs
Publication statusPublished - Apr 10 2019

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Melanoma
Disease-Free Survival
Incidence
Survival
Therapeutics
Disease Progression
Safety
ipilimumab
nivolumab

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Evaluation of Two Dosing Regimens for Nivolumab in Combination With Ipilimumab in Patients With Advanced Melanoma : Results From the Phase IIIb/IV CheckMate 511 Trial. / Lebbé, Celeste; Meyer, Nicolas; Mortier, Laurent; Marquez-Rodas, Ivan; Robert, Caroline; Rutkowski, Piotr; Menzies, Alexander M; Eigentler, Thomas; Ascierto, Paolo A; Smylie, Michael; Schadendorf, Dirk; Ajaz, Mazhar; Svane, Inge Marie; Gonzalez, Rene; Rollin, Linda; Lord-Bessen, Jennifer; Saci, Abdel; Grigoryeva, Elena; Pigozzo, Jacopo.

In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Vol. 37, No. 11, 10.04.2019, p. 867-875.

Research output: Contribution to journalArticle

Lebbé, C, Meyer, N, Mortier, L, Marquez-Rodas, I, Robert, C, Rutkowski, P, Menzies, AM, Eigentler, T, Ascierto, PA, Smylie, M, Schadendorf, D, Ajaz, M, Svane, IM, Gonzalez, R, Rollin, L, Lord-Bessen, J, Saci, A, Grigoryeva, E & Pigozzo, J 2019, 'Evaluation of Two Dosing Regimens for Nivolumab in Combination With Ipilimumab in Patients With Advanced Melanoma: Results From the Phase IIIb/IV CheckMate 511 Trial', Journal of clinical oncology : official journal of the American Society of Clinical Oncology, vol. 37, no. 11, pp. 867-875. https://doi.org/10.1200/JCO.18.01998
Lebbé, Celeste ; Meyer, Nicolas ; Mortier, Laurent ; Marquez-Rodas, Ivan ; Robert, Caroline ; Rutkowski, Piotr ; Menzies, Alexander M ; Eigentler, Thomas ; Ascierto, Paolo A ; Smylie, Michael ; Schadendorf, Dirk ; Ajaz, Mazhar ; Svane, Inge Marie ; Gonzalez, Rene ; Rollin, Linda ; Lord-Bessen, Jennifer ; Saci, Abdel ; Grigoryeva, Elena ; Pigozzo, Jacopo. / Evaluation of Two Dosing Regimens for Nivolumab in Combination With Ipilimumab in Patients With Advanced Melanoma : Results From the Phase IIIb/IV CheckMate 511 Trial. In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2019 ; Vol. 37, No. 11. pp. 867-875.
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title = "Evaluation of Two Dosing Regimens for Nivolumab in Combination With Ipilimumab in Patients With Advanced Melanoma: Results From the Phase IIIb/IV CheckMate 511 Trial",
abstract = "PURPOSE: Nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (NIVO1+IPI3) is approved for first-line treatment of patients with advanced melanoma in several countries. We conducted a phase IIIb/IV study (CheckMate 511) to determine if nivolumab 3 mg/kg plus ipilimumab 1 mg/kg (NIVO3+IPI1) improves the safety profile of the combination.PATIENTS AND METHODS: Patients (N = 360) age 18 years or older with previously untreated, unresectable stage III or IV melanoma were randomly assigned 1:1 to NIVO3+IPI1 or NIVO1+IPI3 once every 3 weeks for four doses. After 6 weeks, all patients received NIVO 480 mg once every 4 weeks until disease progression or unacceptable toxicity. The primary end point was a comparison of the incidence of treatment-related grade 3 to 5 adverse events (AEs) between groups. Secondary end points included descriptive analyses of objective response rate, progression-free survival, and overall survival. The study was not designed to formally demonstrate noninferiority of NIVO3+IPI1 to NIVO1+IPI3 for efficacy end points.RESULTS: At a minimum follow-up of 12 months, incidence of treatment-related grade 3 to 5 AEs was 34{\%} with NIVO3+IPI1 versus 48{\%} with NIVO1+IPI3 ( P = .006). In descriptive analyses, objective response rate was 45.6{\%} in the NIVO3+IPI1 group and 50.6{\%} in the NIVO1+IPI3 group, with complete responses in 15.0{\%} and 13.5{\%} of patients, respectively. Median progression-free survival was 9.9 months in the NIVO3+IPI1 group and 8.9 months in the NIVO1+IPI3 group. Median overall survival was not reached in either group.CONCLUSION: The CheckMate 511 study met its primary end point, demonstrating a significantly lower incidence of treatment-related grade 3-5 AEs with NIVO3+IPI1 versus NIVO1+IPI3. Descriptive analyses showed that there were no meaningful differences between the groups for any efficacy end point, although longer follow up may help to better characterize efficacy outcomes.",
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TY - JOUR

T1 - Evaluation of Two Dosing Regimens for Nivolumab in Combination With Ipilimumab in Patients With Advanced Melanoma

T2 - Results From the Phase IIIb/IV CheckMate 511 Trial

AU - Lebbé, Celeste

AU - Meyer, Nicolas

AU - Mortier, Laurent

AU - Marquez-Rodas, Ivan

AU - Robert, Caroline

AU - Rutkowski, Piotr

AU - Menzies, Alexander M

AU - Eigentler, Thomas

AU - Ascierto, Paolo A

AU - Smylie, Michael

AU - Schadendorf, Dirk

AU - Ajaz, Mazhar

AU - Svane, Inge Marie

AU - Gonzalez, Rene

AU - Rollin, Linda

AU - Lord-Bessen, Jennifer

AU - Saci, Abdel

AU - Grigoryeva, Elena

AU - Pigozzo, Jacopo

PY - 2019/4/10

Y1 - 2019/4/10

N2 - PURPOSE: Nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (NIVO1+IPI3) is approved for first-line treatment of patients with advanced melanoma in several countries. We conducted a phase IIIb/IV study (CheckMate 511) to determine if nivolumab 3 mg/kg plus ipilimumab 1 mg/kg (NIVO3+IPI1) improves the safety profile of the combination.PATIENTS AND METHODS: Patients (N = 360) age 18 years or older with previously untreated, unresectable stage III or IV melanoma were randomly assigned 1:1 to NIVO3+IPI1 or NIVO1+IPI3 once every 3 weeks for four doses. After 6 weeks, all patients received NIVO 480 mg once every 4 weeks until disease progression or unacceptable toxicity. The primary end point was a comparison of the incidence of treatment-related grade 3 to 5 adverse events (AEs) between groups. Secondary end points included descriptive analyses of objective response rate, progression-free survival, and overall survival. The study was not designed to formally demonstrate noninferiority of NIVO3+IPI1 to NIVO1+IPI3 for efficacy end points.RESULTS: At a minimum follow-up of 12 months, incidence of treatment-related grade 3 to 5 AEs was 34% with NIVO3+IPI1 versus 48% with NIVO1+IPI3 ( P = .006). In descriptive analyses, objective response rate was 45.6% in the NIVO3+IPI1 group and 50.6% in the NIVO1+IPI3 group, with complete responses in 15.0% and 13.5% of patients, respectively. Median progression-free survival was 9.9 months in the NIVO3+IPI1 group and 8.9 months in the NIVO1+IPI3 group. Median overall survival was not reached in either group.CONCLUSION: The CheckMate 511 study met its primary end point, demonstrating a significantly lower incidence of treatment-related grade 3-5 AEs with NIVO3+IPI1 versus NIVO1+IPI3. Descriptive analyses showed that there were no meaningful differences between the groups for any efficacy end point, although longer follow up may help to better characterize efficacy outcomes.

AB - PURPOSE: Nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (NIVO1+IPI3) is approved for first-line treatment of patients with advanced melanoma in several countries. We conducted a phase IIIb/IV study (CheckMate 511) to determine if nivolumab 3 mg/kg plus ipilimumab 1 mg/kg (NIVO3+IPI1) improves the safety profile of the combination.PATIENTS AND METHODS: Patients (N = 360) age 18 years or older with previously untreated, unresectable stage III or IV melanoma were randomly assigned 1:1 to NIVO3+IPI1 or NIVO1+IPI3 once every 3 weeks for four doses. After 6 weeks, all patients received NIVO 480 mg once every 4 weeks until disease progression or unacceptable toxicity. The primary end point was a comparison of the incidence of treatment-related grade 3 to 5 adverse events (AEs) between groups. Secondary end points included descriptive analyses of objective response rate, progression-free survival, and overall survival. The study was not designed to formally demonstrate noninferiority of NIVO3+IPI1 to NIVO1+IPI3 for efficacy end points.RESULTS: At a minimum follow-up of 12 months, incidence of treatment-related grade 3 to 5 AEs was 34% with NIVO3+IPI1 versus 48% with NIVO1+IPI3 ( P = .006). In descriptive analyses, objective response rate was 45.6% in the NIVO3+IPI1 group and 50.6% in the NIVO1+IPI3 group, with complete responses in 15.0% and 13.5% of patients, respectively. Median progression-free survival was 9.9 months in the NIVO3+IPI1 group and 8.9 months in the NIVO1+IPI3 group. Median overall survival was not reached in either group.CONCLUSION: The CheckMate 511 study met its primary end point, demonstrating a significantly lower incidence of treatment-related grade 3-5 AEs with NIVO3+IPI1 versus NIVO1+IPI3. Descriptive analyses showed that there were no meaningful differences between the groups for any efficacy end point, although longer follow up may help to better characterize efficacy outcomes.

U2 - 10.1200/JCO.18.01998

DO - 10.1200/JCO.18.01998

M3 - Article

VL - 37

SP - 867

EP - 875

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 11

ER -