PMID- 30811280 OWN - NLM STAT- MEDLINE DCOM- 20200219 LR - 20200309 IS - 1527-7755 (Electronic) IS - 0732-183X (Print) IS - 0732-183X (Linking) VI - 37 IP - 11 DP - 2019 Apr 10 TI - 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. PG - 867-875 LID - 10.1200/JCO.18.01998 [doi] 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. FAU - Lebbe, Celeste AU - Lebbe C AD - 1 Saint-Louis Hospital, Institut National de la Sante et de la Recherche Medicale U976, Universite Paris Diderot, Paris, France. FAU - Meyer, Nicolas AU - Meyer N AD - 2 Universite Paul Sabatier-Toulouse III, Institut National de la Sante et de la Recherche Medicale Unite Mixte de Recherche 1037-CRCT, Toulouse, France. FAU - Mortier, Laurent AU - Mortier L AD - 3 Universite de Lille, Institut National de la Sante et de la Recherche Medicale U1189, Lille, France. FAU - Marquez-Rodas, Ivan AU - Marquez-Rodas I AD - 4 Hospital General Universitario Gregorio Maranon, Madrid, Spain. FAU - Robert, Caroline AU - Robert C AD - 5 Gustave Roussy, Institut National de la Sante et de la Recherche Medicale U981, Paris, France. FAU - Rutkowski, Piotr AU - Rutkowski P AD - 6 Maria Sklodowska-Curie Institute-Oncology Center, Warsaw, Poland. FAU - Menzies, Alexander M AU - Menzies AM AD - 7 Melanoma Institute Australia, University of Sydney, and Royal North Shore and Mater Hospitals, Sydney, New South Wales, Australia. FAU - Eigentler, Thomas AU - Eigentler T AD - 8 University Hospital Tubingen, Tubingen, Germany. FAU - Ascierto, Paolo A AU - Ascierto PA AD - 9 Istituto Nazionale Tumori-Istituto di Ricovero e Cura a Carattere Scientifico Fondazione G. Pascale, Naples, Italy. FAU - Smylie, Michael AU - Smylie M AD - 10 Cross Cancer Institute, Edmonton, Alberta, Canada. FAU - Schadendorf, Dirk AU - Schadendorf D AD - 11 University Hospital, Essen, Germany. AD - 12 German Cancer Consortium, Heidelberg, Germany. FAU - Ajaz, Mazhar AU - Ajaz M AD - 13 St George's University Hospitals National Health Service Foundation Trust, Tooting, London, United Kingdom. FAU - Svane, Inge Marie AU - Svane IM AD - 14 Herlev Hospital, University of Copenhagen, Herlev, Denmark. FAU - Gonzalez, Rene AU - Gonzalez R AD - 15 University of Colorado, Denver, CO. FAU - Rollin, Linda AU - Rollin L AD - 16 Bristol-Myers Squibb, Princeton, NJ. FAU - Lord-Bessen, Jennifer AU - Lord-Bessen J AD - 16 Bristol-Myers Squibb, Princeton, NJ. FAU - Saci, Abdel AU - Saci A AD - 16 Bristol-Myers Squibb, Princeton, NJ. FAU - Grigoryeva, Elena AU - Grigoryeva E AD - 16 Bristol-Myers Squibb, Princeton, NJ. FAU - Pigozzo, Jacopo AU - Pigozzo J AD - 17 Veneto Institute of Oncology-Istituto di Ricovero e Cura a Carattere Scientifico, Padua, Italy. LA - eng SI - ClinicalTrials.gov/NCT02714218 PT - Clinical Trial, Phase III PT - Clinical Trial, Phase IV PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20190227 PL - United States TA - J Clin Oncol JT - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JID - 8309333 RN - 0 (Antineoplastic Agents, Immunological) RN - 0 (Ipilimumab) RN - 31YO63LBSN (Nivolumab) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antineoplastic Agents, Immunological/*administration & dosage/adverse effects MH - Antineoplastic Combined Chemotherapy Protocols/administration & dosage/*therapeutic use MH - Disease Progression MH - Double-Blind Method MH - Drug Administration Schedule MH - Female MH - Humans MH - Ipilimumab/*administration & dosage/adverse effects MH - Male MH - Melanoma/*drug therapy/pathology MH - Middle Aged MH - Neoplasm Staging MH - Nivolumab/*administration & dosage/adverse effects MH - Progression-Free Survival MH - Skin Neoplasms/*drug therapy/pathology MH - Time Factors MH - Young Adult PMC - PMC6455714 EDAT- 2019/02/28 06:00 MHDA- 2020/02/20 06:00 PMCR- 2019/02/27 CRDT- 2019/02/28 06:00 PHST- 2019/02/28 06:00 [pubmed] PHST- 2020/02/20 06:00 [medline] PHST- 2019/02/28 06:00 [entrez] PHST- 2019/02/27 00:00 [pmc-release] AID - 1801998 [pii] AID - 10.1200/JCO.18.01998 [doi] PST - ppublish SO - J Clin Oncol. 2019 Apr 10;37(11):867-875. doi: 10.1200/JCO.18.01998. Epub 2019 Feb 27.