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

Y1 - 2019

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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antineoplastic Agents, Immunological/administration & dosage

KW - Antineoplastic Combined Chemotherapy Protocols/administration & dosage

KW - Disease Progression

KW - Double-Blind Method

KW - Drug Administration Schedule

KW - Female

KW - Humans

KW - Ipilimumab/administration & dosage

KW - Male

KW - Melanoma/drug therapy

KW - Middle Aged

KW - Neoplasm Staging

KW - Nivolumab/administration & dosage

KW - Progression-Free Survival

KW - Skin Neoplasms/drug therapy

KW - Time Factors

KW - Young Adult

U2 - 10.1200/JCO.18.01998

DO - 10.1200/JCO.18.01998

M3 - Journal article

C2 - 30811280

VL - 37

SP - 867

EP - 875

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 11

ER -